摘要 :
In recent years, much effort has focused on the early stages of aggregation and the formation of amyloid oligomers. Aggregation processes for these proteins are complex and their non-equilibrium nature makes any experimental study...
展开
In recent years, much effort has focused on the early stages of aggregation and the formation of amyloid oligomers. Aggregation processes for these proteins are complex and their non-equilibrium nature makes any experimental study very difficult. Under these conditions, simulations provide a useful alternative for understanding the dynamics of the early stages of oligomerization. Here, we focus on the non-Aβ amyloid component (NAC) of the monomer, dimer, and trimer of α-synuclein, an important 35-residue sequence involved in the aggregation and fibrillation of this protein associated with Parkinson’s disease. Using Hamiltonian and temperature replica exchange molecular dynamics simulations combined with the coarse grained Optimized Potential for Efficient peptide structure Prediction potential, we identify the role of the various regions and the secondary structures for the onset of oligomerization. For this sequence, we clearly observe the passage from α-helix to β-sheet, a characteristic transition of amyloid proteins. More precisely, we find that the NAC monomer is highly structured with two α-helical regions, between residues 2-13 and 19-25. As the dimer and trimer form, β-sheet structures between residues 2-14 and 26-34 appear and rapidly structure the system. The resulting conformations are much more structured than similar dimers and trimers of β-amyloid and amylin proteins and yet display a strong polymorphism at these early stages of aggregation. In addition to its inherent experimental interest, comparison with other sequences shows that NAC could be a very useful numerical model for understanding the onset of aggregation.
收起
摘要 :
Early stage HCC has generally been defined as the “Milan criteria”: a solitary tumor ≤ 5 cm in size, or ≤ 3 tumors each ≤ 3 cm in size and no evidence of gross vascular invasion. HCC is now increasingly detected at earlier st...
展开
Early stage HCC has generally been defined as the “Milan criteria”: a solitary tumor ≤ 5 cm in size, or ≤ 3 tumors each ≤ 3 cm in size and no evidence of gross vascular invasion. HCC is now increasingly detected at earlier stages. In addition, both liver transplantation and percutaneous ablative therapies have emerged as effective alternatives to hepatic resection. As a result, the ideal treatment strategy for patients with early stage HCC, particularly in the setting of well-preserved hepatic function, has become increasingly controversial. In the recent studies, the survival rates for transplantation in early stage HCC patients are excellent. However, when intention-to-treat analysis is used, dropouts from the waiting list due to death or disease progression clearly diminish long-term survival results and therefore patients are unlikely to benefit from liver transplantation. In addition, salvage transplantation after HCC resection may be performed without excessive morbidity and may result in equivalent survival rates compared with primary liver transplantation. In some studies, salvage transplantation may be feasible in up to 75-80% of patients with recurrence following hepatic resection. Similarly, locoregional therapies serve to sustain patients with HCC on the waiting list until a transplantation become available. While RFA and TACE are commonly used to prevent dropout, pretransplant therapy has not been associated with improved overall survival or disease-free survival due to persistenceof viable tumor. It is important to note that, while resection is a more invasive procedure, the benefit that it holds over nonresectional therapies is the complete removal of the tumor allowing for subsequent detailed pathologic examination of both the tumor and surrounding liver parenchyma. In conclusion, in patients with well-preserved hepatic function, liver resection remains the most appropriate and effective treatment.
收起
摘要 :
Purpose?The aim of this article was to study survival outcomes of early-stage cervical cancer patients and impact on survival after restaging them as per International Federation of Gynecology and Obstetrics (FIGO) 2018. Materials...
展开
Purpose?The aim of this article was to study survival outcomes of early-stage cervical cancer patients and impact on survival after restaging them as per International Federation of Gynecology and Obstetrics (FIGO) 2018. Materials and Methods?A retrospective study was conducted from June 1, 2013 to May 31, 2018 in a tertiary care hospital in North India. One-hundred patients of early-stage cervical cancer (as per FIGO 2009 staging) who had been treated by surgery followed by risk based tailored adjuvant therapy in our hospital were evaluated. The clinicopathological features and survival outcomes of these patients were analyzed. These patients were then restaged as per new FIGO 2018 staging and survival outcomes between two FIGO classifications were compared. Results?The median age of the study population was 52.5 years with median follow-up of 62.1 months. Ninety percent of our patients had more than 2 years follow-up and 59% had more than 5 years follow-up. The overall survival and relapse-free survival were 87.5 and 91.4%, respectively. The study population was then reclassified according to new FIGO 2018 staging. It was seen that the patients with stage IB1and IB2 cervical cancer had overall survival of 91.1 and 90%, respectively. The overall survival of stage IB3 was 80% and the survival of stage IIIC1 was only 60%. Conclusion?The new FIGO 2018 classification has a significant effect on survival outcome and in prognostication of patients with cervical cancer.
收起
摘要 :
Objective. Although 5-year survival for early-stage ovarian cancer is favorable, prognosis at recurrence is poor, necessitating appropriate initial management. We examined the patterns of care and the impact of the duration of che...
展开
Objective. Although 5-year survival for early-stage ovarian cancer is favorable, prognosis at recurrence is poor, necessitating appropriate initial management. We examined the patterns of care and the impact of the duration of chemotherapy on survival for women with early-stage ovarian cancer.
收起
摘要 :
Objective. The value of surgical staging of apparent early stage epithelial ovarian carcinoma (EOC) is unclear. The aim of this study was to evaluate the importance of surgical staging on the stage of disease and treatment plan.
摘要 :
Objective The aim of this survey was to acquire an overview of the current management of cervical cancer with an emphasis on the early disease stages.
摘要 :
Newly obtained U-Pb and Sm-Nd isotopic data on Early Precambrian metamorphic and granitoid complexes in the southwestern margin of the Siberian craton (Sharyzhalgai basement uplift) are synthe-sized in order to elucidate the crust...
展开
Newly obtained U-Pb and Sm-Nd isotopic data on Early Precambrian metamorphic and granitoid complexes in the southwestern margin of the Siberian craton (Sharyzhalgai basement uplift) are synthe-sized in order to elucidate the crustal evolution starting at the Paleoarchean (similar to 3.6 Ga) to Late Paleoproterozoic (similar to 1.85 Ga), evaluate the lateral extent of the Paleo-Mesoarchean crust, and identify major stages in its growth and recycling. Two crustal growth stages were determined in the Onot and Bulun granite-greenstone terranes: at 3.6-3.3 and 2.8-2.9 Ga. The earliest recycling processes (at similar to 3.4 and 3.2 Ga) involved partial melting, metamorphism, and migmatization and produced a stable continental crust. Crustal growth in the Mesoarchean (similar to 2.8-2.9 Ga) due to basaltoid magmatism was associated with the recycling of the Paleoarchean crust, which served as a source of felsic melts and of detrital material for terrigenous sediments. The Archean crust of the Irkut granulite-gneiss terrane was formed by two pulses of intermediate-felsic and basic volcanism at similar to 3.6-3.4 and similar to 2.7 Ga. In the terminal Archean (at similar to 2.55 Ga), the preexisting crust was involved in metamorphic and magmatic processes. Traces of recycling of the Paleoproterozoic crust are identified in the isotopic parameters of the intermediate-felsic granulites. Two discrete stages in the influx of juvenile material are identified in the Paleoarchean: at similar to 2.0 and 1.88-1.85 Ga, with the latter stage associated with the large-scale recycling of the Archean crust during the origin of granitoids.
收起
摘要 :
Objective: The objective of this study was to determine the efficacy of 3 previously described ovarian cancer serum biomarkers (apolipoprotein-1 [ApoA-I], prealbumin [TTR], transferrin [TF]) in the detection of endometrioid and pa...
展开
Objective: The objective of this study was to determine the efficacy of 3 previously described ovarian cancer serum biomarkers (apolipoprotein-1 [ApoA-I], prealbumin [TTR], transferrin [TF]) in the detection of endometrioid and papillary serous adenocarcinoma of the endometrium. Study Design: ApoA-I, TTR, and TF levels were measured in serum samples that were obtained from 433 individuals that included 90 women with normal endometrium, 210 women with early-stage endometrial cancer, and 133 women with late-stage endometrial cancer. Multivariate regression models were constructed to evaluate the usefulness of the biomarkers in the detection of endometrial cancer. Results: ApoA-I, TTR, and TF distinguished normal samples from early-stage endometrial cancer with a sensitivity of 71% (specificity, 88%) and normal samples from late stage endometrial cancer with a sensitivity of 82% (specificity, 86%). Conclusion: The biomarker panel that consists of ApoA-I, TTR, and TF may prove to be a useful clinical tool for the detection of endometrial cancer.
收起
摘要 :
The tea bag method provides a replicable and standardized method to study the effect of environmental variables on the decomposition of standard litter, which enables comparison of organic matter decomposition rates on a large sca...
展开
The tea bag method provides a replicable and standardized method to study the effect of environmental variables on the decomposition of standard litter, which enables comparison of organic matter decomposition rates on a large scale. However, it remains uncertain whether tea bag decomposition in response to wetness is representative of that of local litters. We performed incubation experiments to examine whether the effect of soil water on tea bag decomposition becomes inhibitory at higher water contents, as is the case in local leaf litters. In addition, we performed field studies in a mixed forest and cedar plantation in Japan to compare two litter bag mesh sizes: 0.25-mm mesh, the size previously used by a major manufacturer of tea bags (Lipton), and nonwoven bags with mesh sizes finer than 0.25 mm, which are currently produced by Lipton. Both green tea and rooibos tea exhibited higher decomposition rates at higher water contents, but decomposition was inhibited at the highest water content; this was in contrast to our hypothesis based on a field observation but consistent with conceptual models of local litters. The nonwoven tea bags did not show lower decomposition rates, despite the finer mesh size. Rather, the nonwoven rooibos tea bags exhibited slightly higher decomposition rates than the 0.25-mm mesh bags in the cedar plantation, possibly due to a greater abundance of microorganisms that decompose litters in the nonwoven bags, due to the decrease in predation by mesofauna. Our findings provide essential information for future studies of tea bag decomposition.
收起
摘要 :
The general impression about gallbladder carcinomas is that they are uniformly fatal; however, for the early forms, an entirely different picture indicating a very good prognosis is evolving from the high-incidence regions. We sub...
展开
The general impression about gallbladder carcinomas is that they are uniformly fatal; however, for the early forms, an entirely different picture indicating a very good prognosis is evolving from the high-incidence regions. We subjected 190 early gallbladder carcinomas (EGBC), defined as carcinomas confined to and above the tunica muscularis (AJCC's Tis, T1a, and T1b), and identified in cholecystectomy specimens sampled entirely according to an established protocol, to detailed analysis. Average patient age was 57.9 years (29–95). In more than half of the cases (114/190; 60 %), the tumor was inapparent by gross examination. In 81 cases (42.6 %), carcinomatous epithelium abutted the muscularis, whereas 57.4 % (n = 109) were qualified as intramucosal with no overt contiguity with muscularis. Intraepithelial extension into Rokitansky–Aschoff sinuses (RAS) was found in 34 cases (17.8 %). At the time of data analysis, 171 patients (99 %) were alive. Overall actuarial survival was 92.3 % at 5 years and 90.4 % at 10 years. The 5- and 10-year actuarial survival rates of the intramucosal group (93.2 and 92.1 %, respectively) were not statistically different from that of the muscle-abutting group (89.7 % and 88.2 % ; p = 0.334). Patients with RAS involvement had a significantly shorter survival than those without (p < 0.001). Of the 33 patients with RAS involvement, 13 (39 %) died of disease, whereas only 6 of the 154 patients (4 %) without RAS involvement died of disease. Disease-related mortality in these cases occurred relatively late (median 48 months). EGBC has a very good prognosis with a 90 % 10-year survival rate. It is seen on average in patients almost a decade younger than those with advanced cancers. RAS involvement is an independent prognostic factor, and additional surgery may have to be considered for such cases. Occasional recurrences are encountered several years later, which suggests a field-effect phenomenon and warrants long-term follow-up.
收起
原文获取