Prognostic factors and treatment of neuroendocrine tumors of the uterine cervix based on the FIGO 2018 staging system: a single-institution study of 172 patients

Objective This study aimed to explore the prognostic factors and outcomes of patients with neuroendocrine tumors (NETs) of the cervix and to determine appropriate treatment. Methods A single-institution retrospective analysis of 172 patients with NETs was performed based on the new International Federation of Gynecology and Obstetrics (FIGO 2018) staging system. Results Among the 172 eligible patients, 161 were diagnosed with small cell neuroendocrine carcinoma (SCNEC), six with large cell neuroendocrine carcinoma, four with typical carcinoid tumors and one with SCNEC combined with an atypical carcinoid tumor. According to the FIGO 2018 staging guidelines, 31 were stage I, 66 were stage II, 57 were stage III, and 18 were stage IV. The 5-year survival rates of patients with stage I–IV disease were 74.8%, 56.2%, 41.4% and 0%, respectively. The 5-year progression-free survival rates of patients with stage I–IV disease were 63.8%, 54.5%, 30.8% and 0%, respectively. In the multivariate analysis, advanced FIGO stage, large tumor and older age were identified as independent variables for 5-year survival in patients with stage I–IV disease. FIGO stage, tumor size and para-aortic lymph node metastasis were independent prognostic factors for 5-year progression-free survival in patients with stage I–IV disease. For the patients receiving surgery (n = 108), tumor size and pelvic lymph node metastasis were independent prognostic factors for 5-year survival, and pelvic lymph node metastasis for 5-year progression-free survival. In stage IVB, at least six cycles of chemotherapy (n = 7) was associated with significantly better 2-year OS (83.3% vs. 9.1%, p < 0.001) and 2-year PFS (57.1% vs. 0%, p = 0.01) than fewer than six cycles of chemotherapy(n = 11). Conclusion Advanced FIGO stage, large tumor, older age and lymph node metastasis are independent prognostic factors for NETs of the cervix. The TP/TC and EP regimens were the most commonly used regimens, with similar efficacies and toxicities. Standardized and complete multimodality treatment may improve the survival of patients with NETs

Altered dynamic functional network connectivity in drug-naïve Parkinson’s disease patients with excessive daytime sleepiness

BackgroundExcessive daytime sleepiness (EDS) is a frequent nonmotor symptoms of Parkinson’s disease (PD), which seriously affects the quality of life of PD patients and exacerbates other nonmotor symptoms. Previous studies have used static analyses of these resting-state functional magnetic resonance imaging (rs-fMRI) data were measured under the assumption that the intrinsic fluctuations during MRI scans are stationary. However, dynamic functional network connectivity (dFNC) analysis captures time-varying connectivity over short time scales and may reveal complex functional tissues in the brain.PurposeTo identify dynamic functional connectivity characteristics in PD-EDS patients in order to explain the underlying neuropathological mechanisms.MethodsBased on rs-fMRI data from 16 PD patients with EDS and 41 PD patients without EDS, we applied the sliding window approach, k-means clustering and independent component analysis to estimate the inherent dynamic connectivity states associated with EDS in PD patients and investigated the differences between groups. Furthermore, to assess the correlations between the altered temporal properties and the Epworth sleepiness scale (ESS) scores.ResultsWe found four distinct functional connectivity states in PD patients. The patients in the PD-EDS group showed increased fractional time and mean dwell time in state IV, which was characterized by strong connectivity in the sensorimotor (SMN) and visual (VIS) networks, and reduced fractional time in state I, which was characterized by strong positive connectivity intranetwork of the default mode network (DMN) and VIS, while negative connectivity internetwork between the DMN and VIS. Moreover, the ESS scores were positively correlated with fraction time in state IV.ConclusionOur results indicated that the strong connectivity within and between the SMN and VIS was characteristic of EDS in PD patients, which may be a potential marker of pathophysiological features related to EDS in PD patients

Impact of fully coupled hydrology-atmosphere processes on atmosphere conditions: investigating the performance of the WRF-Hydro model in the Three River source region on the Tibetan Plateau, China

The newly developed WRF-Hydro model is a fully coupled atmospheric and hydrological processes model suitable for studying the intertwined atmospheric hydrological processes. This study utilizes the WRF-Hydro system on the Three-River source region. The Nash-Sutcliffe efficiency for the runoff simulation is 0.55 compared against the observed daily discharge amount of three stations. The coupled WRF-Hydro simulations are better than WRF in terms of six ground meteorological elements and turbulent heat flux, compared to the data from 14 meteorological stations located in the plateau residential area and two flux stations located around the lake. Although WRF-Hydro overestimates soil moisture, higher anomaly correlation coefficient scores (0.955 versus 0.941) were achieved. The time series of the basin average demonstrates that the hydrological module of WRF-hydro functions during the unfrozen period. The rainfall intensity and frequency simulated by WRF-Hydro are closer to global precipitation mission (GPM) data, attributed to higher convective available potential energy (CAPE) simulated by WRF-Hydro. The results emphasized the necessity of a fully coupled atmospheric-hydrological model when investigating land-atmosphere interactions on a complex topography and hydrology region

Ultrathin MOF nanosheet assembled highly oriented microporous membrane as an interlayer for lithium-sulfur batteries

Abstract(#br)Lithium sulfur (Li-S) batteries are attracting increasing attentions as promising next-generation rechargeable batteries. However, the rapid capacity fading of sulfur cathodes caused by the shuttling of polysulfide intermediates between the cathodes and anodes restricts the application of Li-S batteries. In this work, a facile wet-chemistry method is developed for the direct synthesis of few-molecular-layer thin metal-organic framework (MOF) nanosheets without using surfactant. By assembling these ultrathin MOF nanosheets with a facile vacuum filtration method, a highly oriented and flexible MOF membrane with favorable mechanical properties is achieved for the first time. The excellent features make the as-prepared MOF nanosheets ideal to fabricate lightweight interlayer modified separators for suppressing the polysulfide shuttling of Li-S batteries. When using the MOF membrane modified separator, the Li-S batteries made from commercial carbon materials exhibits the significantly enhanced cycling stabilities. This work brings new opportunities for the synthesis and application of MOF materials

La matriz extracelular: morfología, función y biotensegridad (parte I)

La matriz extracelular (MEC) representa una red tridimensional que engloba todos los órganos, tejidos y células del organismo. Constituye un filtro biofísico de protección, nutrición e inervación celular y el terreno para la respuesta inmune, angiogénesis, fibrosis y regeneración tisular. Y representa el medio de transmisión de fuerzas mecánicas a la membrana basal, que a través de las integrinas soporta el sistema de tensegridad y activa los mecanismos epigenéticos celulares. La alteración de la MEC supone la pérdida de su función de filtro eficaz, nutrición, eliminación, denervación celular, pérdida de la capacidad de regeneración y cicatrización y alteración de la transmisión mecánica o mecanotransducción. También la pérdida del sustrato para una correcta respuesta inmune ante agentes infecciosos, tumorales y tóxicos. Los tumores son tejidos funcionales conectados y dependientes del microambiente. El microambiente tumoral, constituido por la MEC, células del estroma y la propia respuesta inmune, son determinantes de la morfología y clasificación tumoral, agresividad clínica, pronóstico y respuesta al tratamiento del tumor. Tanto en condiciones fisiológicas como patológicas, la comunicación recíproca entre células del estroma y el parénquima dirige la expresión génica. La capacidad oncogénica del estroma procede tanto de los fibroblastos asociados al tumor como de la celularidad de la respuesta inmune y la alteración de la tensegridad por la MEC. La transición epitelio-mesenquimal es el cambio que transforma una célula normal o «benigna» en «maligna». El citoesqueleto pseudomesenquimal otorga las propiedades de migración, invasión y diseminación. Y viceversa, el fenotipo maligno es reversible a través de la corrección de las claves que facilita el microambiente tumoral.Extracellular matrix (ECM) is a three-dimensional network that envelopes all the organs, tissues and cells of the body. A biophysical filter that provides protection, nutrition and cell innervation, it is the site for immune response, angiogenesis, fibrosis and tissue regeneration. It is also the transport medium for mechanical forces to the basal membrane through integrins that support the tensegrity system, activating cellular epigenetic mechanisms. The disruption of the ECM leads to a functional loss of nutrition, elimination, cell innervation, regenerative capacity and wound healing as well as alterations in mechanical transduction. This loss also disrupts the immune response to pathogens, tumour cells and toxins. Tumours are functionally connected tissues which depend on the microenvironment. This tumour microenvironment, made up of ECM, stromal cells and the immune response, determines the morphology and tumour histopathological classification, clinical behaviour, prognosis and immune response to the tumour. Both in physiological and pathological conditions, reciprocity in the communication between stromal and parenchymal cells determine gene expression. The oncogenic capacity of the stroma depends on tumour associated fibroblasts, immune system cellularity and disruption of tensegrity by ECM. Epithelial-mesenchymal transition is the change that transforms a normal or benign cell into a malignant cell. The «pseudo-mensenchymal» cytoskeleton is responsible for migration, invasion and dissemination, and vice-versa, the malignant phenotype is reversible through the correction of the microenvironmental factors that favour tumour growth.Noguera Salva, Rosa, [email protected]

Phenotypic Plasticity and Effects of Selection on Cell Division Symmetry in Escherichia coli

Aging has been demonstrated in unicellular organisms and is presumably due to asymmetric distribution of damaged proteins and other components during cell division. Whether the asymmetry-induced aging is inevitable or an adaptive and adaptable response is debated. Although asymmetric division leads to aging and death of some cells, it increases the effective growth rate of the population as shown by theoretical and empirical studies. Mathematical models predict on the other hand, that if the cells divide symmetrically, cellular aging may be delayed or absent, growth rate will be reduced but growth yield will increase at optimum repair rates. Therefore in nutritionally dilute (oligotrophic) environments, where growth yield may be more critical for survival, symmetric division may get selected. These predictions have not been empirically tested so far. We report here that Escherichia coli grown in oligotrophic environments had greater morphological and functional symmetry in cell division. Both phenotypic plasticity and genetic selection appeared to shape cell division time asymmetry but plasticity was lost on prolonged selection. Lineages selected on high nutrient concentration showed greater frequency of presumably old or dead cells. Further, there was a negative correlation between cell division time asymmetry and growth yield but there was no significant correlation between asymmetry and growth rate. The results suggest that cellular aging driven by asymmetric division may not be hardwired but shows substantial plasticity as well as evolvability in response to the nutritional environment

On the Resolution of Critical Flow Regions in Inviscid Linear And Nonlinear Instability Calculations

Numerical methods for tackling the inviscid instability problem are discussed. Convergence is demon- strated to be a necessary, but not a sufficient condition for accuracy. Inviscid flow physics set requirements regarding grid-point distribution in order for physically accurate results to be obtained. These requirements are relevant to the viscous problem also and are shown to be related to the resolution of the critical layers. In this respect, high-resolution nonlinear calculations based on the inviscid initial-boundary-value problem are presented for a model shear-layer flow, aiming at identification of the regions that require attention in the course of high-Reynolds-number viscous calculations. The results bear a remarkable resemblance with those pertinent to viscous flow, with a cascade of high-shear regions being shed towards the vortex-core centre as time progresses. In parallel, numerical instability related to the finite-time singularity of the nonlinear equations solved globally contaminates and eventually destroys the simulations, irrespective of resolution

Order 10 4 speedup in global linear instability analysis using matrix formation

A unified solution framework is presented for one-, two- or three-dimensional complex non-symmetric eigenvalue problems, respectively governing linear modal instability of incompressible fluid flows in rectangular domains having two, one or no homogeneous spatial directions. The solution algorithm is based on subspace iteration in which the spatial discretization matrix is formed, stored and inverted serially. Results delivered by spectral collocation based on the Chebyshev-Gauss-Lobatto (CGL) points and a suite of high-order finite-difference methods comprising the previously employed for this type of work Dispersion-Relation-Preserving (DRP) and Padé finite-difference schemes, as well as the Summationby- parts (SBP) and the new high-order finite-difference scheme of order q (FD-q) have been compared from the point of view of accuracy and efficiency in standard validation cases of temporal local and BiGlobal linear instability. The FD-q method has been found to significantly outperform all other finite difference schemes in solving classic linear local, BiGlobal, and TriGlobal eigenvalue problems, as regards both memory and CPU time requirements. Results shown in the present study disprove the paradigm that spectral methods are superior to finite difference methods in terms of computational cost, at equal accuracy, FD-q spatial discretization delivering a speedup of ð (10 4). Consequently, accurate solutions of the three-dimensional (TriGlobal) eigenvalue problems may be solved on typical desktop computers with modest computational effort