Contribution of the microvessel network to the clonal and kinetic profiles of adrenal cortical proliferative lesions

Monoclonal adrenocortical lesions have been characterized by an inverse correlation between proliferation and apoptosis, and polyclonal lesions show a direct correlation. Their relationship with the vascular pattern remains unknown in adrenocortical nodular hyperplasias (ACNHs), adenomas (ACAs), and carcinomas (ACCs). We studied 20 ACNHs, 25 ACAs, and 10 ACCs (World Health Organization classification criteria) from 55 women. The analysis included X-chromosome inactivation assay (on microdissected samples), slide and flow cytometry, and in situ end labeling. Endothelial cells were stained with anti-CD31, and the blood vessel area and density were quantified by image analysis in the same areas. Appropriate tissue controls were run in every case. Regression analyses between kinetic and vascular features were performed in both polyclonal and monoclonal lesions. Polyclonal patterns were observed in 14 of 18 informative ACNHs and 3 of 22 informative ACAs, and monoclonal patterns were seen in 4 of 18 ACNHs, 19 of 22 ACAs, and 9 of 9 ACCs. A progressive increase in microvessel area was observed in the ACNH–ACA–ACC transition but was statistically significant between benign and malignant lesions only (191.36 ± 168.32 v 958.07 ± 1279.86 μm2; P 186 μm2 (P =.0000008). Monoclonal lesions showed parallel trends (but with opposite signs) for microvessel area and density in comparison with proliferation and apoptosis, whereas polyclonal lesions showed inverse trends. In conclusion, the kinetic advantage of monoclonal adrenal cortical lesions (increased proliferation, decreased apoptosis) is maintained by parallel increases in microvessel area and density. HUM PATHOL 32:1232-1239. Copyright © 2001 by W.B. Saunders Compan

Sentiment Analysis of Political Tweets From the 2019 Spanish Elections

The use of sentiment analysis methods has increased in recent years across a wide range of disciplines. Despite the potential impact of the development of opinions during political elections, few studies have focused on the analysis of sentiment dynamics and their characterization from statistical and mathematical perspectives. In this paper, we apply a set of basic methods to analyze the statistical and temporal dynamics of sentiment analysis on political campaigns and assess their scope and limitations. To this end, we gathered thousands of Twitter messages mentioning political parties and their leaders posted several weeks before and after the 2019 Spanish presidential election. We then followed a twofold analysis strategy: (1) statistical characterization using indices derived from well-known temporal and information metrics and methods –including entropy, mutual information, and the Compounded Aggregated Positivity Index– allowing the estimation of changes in the density function of sentiment data; and (2) feature extraction from nonlinear intrinsic patterns in terms of manifold learning using autoencoders and stochastic embeddings. The results show that both the indices and the manifold features provide an informative characterization of the sentiment dynamics throughout the election period. We found measurable variations in sentiment behavior and polarity across the political parties and their leaders and observed different dynamics depending on the parties’ positions on the political spectrum, their presence at the regional or national levels, and their nationalist or globalist aspirations

Clonal patterns in phaeochromocytomas and MEN-2A adrenal medullary hyperplasias: histological and kinetic correlates

The relationship among histological features, cell kinetics, and clonality has not been studied in adrenal medullary hyperplasias (AMHs) and phaeochromocytomas (PCCs). Thirty-four PCCs (23 sporadic and 11 MEN-2A (multiple endocrine neoplasia type 2A)-related tumours, the latter associated with AMH) from females were included in this study. Representative samples were histologically evaluated and microdissected to extract DNA and evaluate the methylation pattern of the androgen receptor alleles. At least two tissue samples (from the peripheral and internal zones in each tumour) were analysed with appropriate tissue controls run in every case. The same areas were selected for MIB-1 staining and in situ end labelling (ISEL). Malignant PCCs were defined by histologically confirmed distant metastases. All monoclonal AMH nodules from the same patient showed the same X-chromosome inactivated. Six sporadic PCCs revealed liver metastases (malignant PCC) and eight additional sporadic PCCs showed periadrenal infiltration (locally invasive PCC). All informative PCCs were monoclonal, except for five locally invasive PCCs and one benign PCC that revealed polyclonal patterns. Those cases also showed a fibroblastic stromal reaction with prominent blood vessels, focal smooth muscle differentiation, and significantly higher MIB-1 (126.8±29.9) and ISEL (50.9±12.8) indices. Concordant X-chromosome inactivation in nodules from a given patient suggests that MEN-2A AMH is a multifocal monoclonal condition. A subgroup of PCCs characterized by balanced methylation of androgen receptor alleles, high cellular turnover, and stromal proliferation also shows locally invasive features. Copyright © 2000 John Wiley & Sons, Ltd

On the Statistical and Temporal Dynamics of Sentiment Analysis

Despite the broad interest and use of sentiment analysis nowadays, most of the conclusions in current literature are driven by simple statistical representations of sentiment scores. On that basis, the generated sentiment evaluation consists nowadays of encoding and aggregating emotional information from a number of individuals and their populational trends. We hypothesized that the stochastic processes aimed to be measured by sentiment analysis systems will exhibit nontrivial statistical and temporal properties. We established an experimental setup consisting of analyzing the short text messages (tweets) of 6 user groups with different nature (universities, politics, musicians, communication media, technological companies, and financial companies), including in each group ten high-intensity users in their regular generation of traffic on social networks. Statistical descriptors were checked to converge at about 2000 messages for each user, for which messages from the last two weeks were compiled using a custom-made tool. The messages were subsequently processed for sentiment scoring in terms of different lexicons currently available and widely used. Not only the temporal dynamics of the resulting score time series per user was scrutinized, but also its statistical description as given by the score histogram, the temporal autocorrelation, the entropy, and the mutual information. Our results showed that the actual dynamic range of lexicons is in general moderate, and hence not much resolution is given within their end-of-scales. We found that seasonal patterns were more present in the time evolution of the number of tweets, but to a much lesser extent in the sentiment intensity. Additionally, we found that the presence of retweets added negligible effects over standard statistical modes, while it hindered informational and temporal patterns. The innovative Compounded Aggregated Positivity Index developed in this work proved to be characteristic for industries and at ..

Prediction of Anti-Glioblastoma Drug-Decorated Nanoparticle Delivery Systems Using Molecular Descriptors and Machine Learning

The theoretical prediction of drug-decorated nanoparticles (DDNPs) has become a very important task in medical applications. For the current paper, Perturbation Theory Machine Learning (PTML) models were built to predict the probability of different pairs of drugs and nanoparticles creating DDNP complexes with anti-glioblastoma activity. PTML models use the perturbations of molecular descriptors of drugs and nanoparticles as inputs in experimental conditions. The raw dataset was obtained by mixing the nanoparticle experimental data with drug assays from the ChEMBL database. Ten types of machine learning methods have been tested. Only 41 features have been selected for 855,129 drug-nanoparticle complexes. The best model was obtained with the Bagging classifier, an ensemble meta-estimator based on 20 decision trees, with an area under the receiver operating characteristic curve (AUROC) of 0.96, and an accuracy of 87% (test subset). This model could be useful for the virtual screening of nanoparticle-drug complexes in glioblastoma. All the calculations can be reproduced with the datasets and python scripts, which are freely available as a GitHub repository from authors. View Full-TextThe APC was funded by IKERDATA, S.L. under grant 3/12/DP/2021/00102—Area 1: Development of innovative business projects, from Provincial Council of Vizcaya (BEAZ for the Creation of Innovative Business Innovative business ventures)

Glycemic markers and relation with arterial stiffness in Caucasian subjects of the MARK study

[EN]BACKGROUND: Effect of prediabetes and normal glucose on arterial stiffness remains controversial. The primary aim of this study was to investigate the relationship of fasting plasma glucose (FPG), postprandial glucose (PG) and glycosylated haemoglobin (HbA1c) with brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) in Caucasian adults. The secondary aim was to analyse this relationship by glycaemic status. METHODS: Cross-sectional study. Setting: Primary care. Participants: 2,233 subjects, 35-74 years. Measures: FPG (mg/dL) and HbA1c (%) of all subjects were measured using standard automated enzymatic methods. PG (mg/dL) was self-measured at home two hours after meals (breakfast, lunch and dinner) for one day using an Accu-chek ® glucometer. CAVI was measured using a VaSera VS-1500® device (Fukuda Denshi), and baPWV was calculated using a validated equation. RESULTS: CAVI and baPWV values were significantly higher in subjects with diabetes mellitus than in glucose normal and prediabetes groups (p<0.001). FPG, PG and HbA1c were positively associated with CAVI and baPWV. The β regression coefficient for: HbA1c was 0.112 (CI 95% 0.068 to 0.155) with CAVI, 0.266 (CI 95% 0.172 to 0.359) with baPWV; for PG was 0.006 (CI 95% 0.004 to 0.009 and for FPG was 0.005 (CI 95% 0.002 to 0.008) with baPWV; and for PG was 0.002 (CI 95% 0.001 to 0.003) and 0.003 (CI 95% 0.002 to 0.004) with CAVI (p<0.01 in all cases). When analysing by hyperglycaemic status, FPG, PG and HbA1c were positively associated with CAVI and baPWV in subjects with type 2 diabetes mellitus. CONCLUSION: FPG, PG and HbA1c show a positive association with CAVI and baPWV, in Caucasian adults with intermediate cardiovascular risk factors. When analysing by hyperglycaemic status, the association is only maintained in subjects with type 2 diabetes mellitus

Presence of Blastocystis in the gut microbiota is associated with cognitive traits and decreased executive function

Growing evidence implicates the gut microbiome in cognition. Blastocystis is a common gut single-cell eukaryote parasite frequently detected in humans but its potential involvement in human pathophysiology has been poorly characterized. Here we describe how the presence of Blastocystis in the gut microbiome was associated with deficits in executive function and altered gut bacterial composition in a discovery (n = 114) and replication cohorts (n = 942). We also found that Blastocystis was linked to bacterial functions related to aromatic amino acids metabolism and folate-mediated pyrimidine and one-carbon metabolism. Blastocystis-associated shifts in bacterial functionality translated into the circulating metabolome. Finally, we evaluated the effects of microbiota transplantation. Donor's Blastocystis subtypes led to altered recipient's mice cognitive function and prefrontal cortex gene expression. In summary, Blastocystis warrant further consideration as a novel actor in the gut microbiome-brain axis

All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS) compared with the general population: 1997Ł2010

Abstract Background: Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIVinfected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. Methods: We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 personyears (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. Results: Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997. Conclusion: Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection

Germline RET 634 Mutation Positive MEN 2A-related C-Cell Hyperplasias Have Genetic Features Consistent with Intraepithelial Neoplasia

C-cell hyperplasias are normally multifocal in multiple endocrine neoplasia type 2A. We compared clonality, microsatellite pattern of tumor suppressor genes, and cellular kinetics of C-cell hyperplasia foci in each thyroid lobe. We selected 11 females from multiple endocrine neoplasia type 2A kindred treated with thyroidectomy due to hypercalcitoninemia. C-cell hyperplasia foci were microdissected for DNA extraction to analyze the methylation pattern of androgen receptor alleles and microsatellite regions (TP53, RB1, WT1, and NF1). Consecutive sections were selected for MIB-1, pRB1, p53, Mdm-2, and p21WAF1 immunostaining, DNA content analysis, and in situ end labeling. Appropriate tissue controls were run. Only two patients had medullary thyroid carcinoma foci. Nine informative C-cell hyperplasia patients showed germline point mutation in RET, eight of them with the same androgen receptor allele preferentially methylated in both lobes. C-cell hyperplasia foci showed heterogeneous DNA deletions revealed by loss of heterozygosity of TP53 (12 of 20), RB1 (6 of 14), and WT1 (4 of 20) and hypodiploid G0/G1 cells (14 of 20), low cellular turnover (MIB-1 index 4.5%, in situ end labeling index 0.03%), and significantly high nuclear area to DNA index ratio. MEN 2A (germline point mutation in RET codon 634) C-cell hyperplasias are monoclonal and genetically heterogeneous and show down-regulated apoptosis, findings consistent with an intraepithelial neoplasia. Concordant X-chromosome inactivation and interstitial gene deletions suggest clone expansions of precursors occurring at a point in embryonic development before divergence of each thyroid lobe and may represent a paradigm for other germline mutations