Author: "A. Simón" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

2,677 results on '"A. Simón"'

1. Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation.

Author: Hollunder, Barbara, Ostrem, Jill, Sahin, Ilkem, Rajamani, Nanditha, Oxenford, Simón, Butenko, Konstantin, Neudorfer, Clemens, Reinhardt, Pablo, Zvarova, Patricia, Polosan, Mircea, Akram, Harith, Vissani, Matteo, Zhang, Chencheng, Sun, Bomin, Navratil, Pavel, Reich, Martin, Volkmann, Jens, Yeh, Fang-Cheng, Baldermann, Juan, Dembek, Till, Visser-Vandewalle, Veerle, Alho, Eduardo, Franceschini, Paulo, Nanda, Pranav, Finke, Carsten, Kühn, Andrea, Dougherty, Darin, Richardson, R, Bergman, Hagai, DeLong, Mahlon, Mazzoni, Alberto, Romito, Luigi, Tyagi, Himanshu, Zrinzo, Ludvic, Joyce, Eileen, Chabardes, Stephan, Li, Ningfei, Horn, Andreas, and Starr, Philip
Subjects: Humans, Deep Brain Stimulation, Brain, Motor Cortex, Parkinson Disease, Brain Mapping
Abstract: Frontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By analyzing which connections were modulated for optimal therapeutic response across these disorders, we segregated the frontal cortex into circuits that had become dysfunctional in each of them. Dysfunctional circuits were topographically arranged from occipital to frontal, ranging from interconnections with sensorimotor cortices in dystonia, the primary motor cortex in Tourettes syndrome, the supplementary motor area in Parkinsons disease, to ventromedial prefrontal and anterior cingulate cortices in obsessive-compulsive disorder. Our findings highlight the integration of deep brain stimulation with brain connectomics as a powerful tool to explore couplings between brain structure and functional impairments in the human brain.
Published: 2024

2. Paclitaxel-Loaded Cationic Fluid Lipid Nanodiscs and Liposomes with Brush-Conformation PEG Chains Penetrate Breast Tumors and Trigger Caspase‑3 Activation

Author: Simón-Gracia, Lorena, Scodeller, Pablo, Fisher, William S, Sidorenko, Valeria, Steffes, Victoria M, Ewert, Kai K, Safinya, Cyrus R, and Teesalu, Tambet
Subjects: Engineering, Chemical Sciences, Physical Sciences, Nanotechnology, Cancer, Bioengineering, Mice, Humans, Animals, Female, Paclitaxel, Liposomes, Tissue Distribution, Caspase 3, Polyethylene Glycols, Lipids, Breast Neoplasms, Drug Carriers, Cell Line, Tumor, Antineoplastic Agents, Phytogenic, chemotherapy, paclitaxel, cationic liposome, PEGylation, fluid lipid disk bicelle, tumor penetration, triple-negative breast cancer, Nanoscience & Nanotechnology, Chemical sciences, Physical sciences
Abstract: Novel approaches are required to address the urgent need to develop lipid-based carriers of paclitaxel (PTX) and other hydrophobic drugs for cancer chemotherapy. Carriers based on cationic liposomes (CLs) with fluid (i.e., chain-melted) membranes (e.g., EndoTAG-1) have shown promise in preclinical and late-stage clinical studies. Recent work found that the addition of a cone-shaped poly(ethylene glycol)-lipid (PEG-lipid) to PTX-loaded CLs (CLsPTX) promotes a transition to sterically stabilized, higher-curvature (smaller) nanoparticles consisting of a mixture of PEGylated CLsPTX and PTX-containing fluid lipid nanodiscs (nanodiscsPTX). These CLsPTX and nanodiscsPTX show significantly improved uptake and cytotoxicity in cultured human cancer cells at PEG coverage in the brush regime (10 mol % PEG-lipid). Here, we studied the PTX loading, in vivo circulation half-life, and biodistribution of systemically administered CLsPTX and nanodiscsPTX and assessed their ability to induce apoptosis in triple-negative breast-cancer-bearing immunocompetent mice. We focused on fluid rather than solid lipid nanodiscs because of the significantly higher solubility of PTX in fluid membranes. At 5 and 10 mol % of a PEG-lipid (PEG5K-lipid, molecular weight of PEG 5000 g/mol), the mixture of PEGylated CLsPTX and nanodiscsPTX was able to incorporate up to 2.5 mol % PTX without crystallization for at least 20 h. Remarkably, compared to preparations containing 2 and 5 mol % PEG5K-lipid (with the PEG chains in the mushroom regime), the particles at 10 mol % (with PEG chains in the brush regime) showed significantly higher blood half-life, tumor penetration, and proapoptotic activity. Our study suggests that increasing the PEG coverage of CL-based drug nanoformulations can improve their pharmacokinetics and therapeutic efficacy.
Published: 2022

3. Anti-miR-518d-5p overcomes liver tumor cell death resistance through mitochondrial activity

Author: Fernández-Tussy, Pablo, Rodríguez-Agudo, Rubén, Fernández-Ramos, David, Barbier-Torres, Lucía, Zubiete-Franco, Imanol, Davalillo, Sergio López de, Herraez, Elisa, Goikoetxea-Usandizaga, Naroa, Lachiondo-Ortega, Sofia, Simón, Jorge, Lopitz-Otsoa, Fernando, Juan, Virginia Gutiérrez-de, McCain, Misti V, Perugorria, Maria J, Mabe, Jon, Navasa, Nicolás, Rodrigues, Cecilia MP, Fabregat, Isabel, Boix, Loreto, Sapena, Victor, Anguita, Juan, Lu, Shelly C, Mato, José M, Banales, Jesus M, Villa, Erica, Reeves, Helen L, Bruix, Jordi, Reig, Maria, Marin, Jose JG, Delgado, Teresa C, and Martínez-Chantar, María L
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Orphan Drug, Liver Disease, Digestive Diseases, Liver Cancer, Rare Diseases, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Animals, Apoptosis, Cell Death, Female, Humans, Liver Neoplasms, Mice, Mice, Nude, MicroRNAs, Mitochondria, Biochemistry and Cell Biology, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract: Dysregulation of miRNAs is a hallmark of cancer, modulating oncogenes, tumor suppressors, and drug responsiveness. The multi-kinase inhibitor sorafenib is one of the first-line drugs for advanced hepatocellular carcinoma (HCC), although the outcome for treated patients is heterogeneous. The identification of predictive biomarkers and targets of sorafenib efficacy are sorely needed. Thus, selected top upregulated miRNAs from the C19MC cluster were analyzed in different hepatoma cell lines compared to immortalized liver human cells, THLE-2 as control. MiR-518d-5p showed the most consistent upregulation among them. Thus, miR-518d-5p was measured in liver tumor/non-tumor samples of two distinct cohorts of HCC patients (n = 16 and n = 20, respectively). Circulating miR-518d-5p was measured in an independent cohort of HCC patients receiving sorafenib treatment (n = 100), where miR-518d-5p was analyzed in relation to treatment duration and patient's overall survival. In vitro and in vivo studies were performed in human hepatoma BCLC3 and Huh7 cells to analyze the effect of miR-518d-5p inhibition/overexpression during the response to sorafenib. Compared with healthy individuals, miR-518d-5p levels were higher in hepatic and serum samples from HCC patients (n = 16) and in an additional cohort of tumor/non-tumor paired samples (n = 20). MiR-518d-5p, through the inhibition of c-Jun and its mitochondrial target PUMA, desensitized human hepatoma cells and mouse xenograft to sorafenib-induced apoptosis. Finally, serum miR-518d-5p was assessed in 100 patients with HCC of different etiologies and BCLC-stage treated with sorafenib. In BCLC-C patients, higher serum miR-518d-5p at diagnosis was associated with shorter sorafenib treatment duration and survival. Hence, hepatic miR-518d-5p modulates sorafenib resistance in HCC through inhibition of c-Jun/PUMA-induced apoptosis. Circulating miR-518d-5p emerges as a potential lack of response biomarker to sorafenib in BCLC-C HCC patients.
Published: 2021

4. Design of a cluster-randomized trial of the effectiveness and cost-effectiveness of metformin on prevention of type 2 diabetes among prediabetic Mexican adults (the PRuDENTE initiative of Mexico City)

Author: Rodríguez, Luis A, Barquera, Simón, Aguilar-Salinas, Carlos A, Sepúlveda-Amor, Jaime, Sánchez-Romero, Luz María, Denova-Gutiérrez, Edgar, Balderas, Nydia, Moreno-Loaeza, Lizbeth, Handley, Margaret A, Basu, Sanjay, López-Arellano, Oliva, Gallardo-Hernández, Alberto, and Schillinger, Dean
Subjects: Health Services and Systems, Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Prevention, Health Disparities, Health Services, Clinical Research, Cost Effectiveness Research, Obesity, Minority Health, Diabetes, Comparative Effectiveness Research, Nutrition, Dissemination and Implementation Research, Clinical Trials and Supportive Activities, Behavioral and Social Science, Women's Health, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, Prevention of disease and conditions, and promotion of well-being, Metabolic and endocrine, Good Health and Well Being, Adult, Aged, Cost-Benefit Analysis, Diabetes Mellitus, Type 2, Humans, Metformin, Mexico, Middle Aged, Prediabetic State, Type 2 diabetes, Cluster trial, Research protocol, Implementation evaluation, Medical and Health Sciences, General Clinical Medicine, Public Health, Biomedical and clinical sciences, Health sciences
Abstract: IntroductionType 2 diabetes (T2D) is a global epidemic, and nations are struggling to implement effective healthcare strategies to reduce the burden. While efficacy studies demonstrate that metformin can reduce incident T2D by half among younger, obese adults with prediabetes, its real-world effectiveness are understudied, and its use for T2D prevention in primary care is low. We describe the design of a pragmatic trial to evaluate the incremental effectiveness of metformin, as an adjunct to a simple lifestyle counseling.MethodsThe "Prevención de la Diabetes con Ejercicio, Nutrición y Tratamiento" [Diabetes Prevention with Exercise, Nutrition and Treatment; PRuDENTE, (Spanish acronym)] is a cluster-randomized trial in Mexico City's public primary healthcare system. The study randomly assigns 51 clinics to deliver one of two interventions for 36 months: 1) lifestyle only; 2) lifestyle plus metformin, to 3060 patients ages 30-65 with impaired fasting glucose and obesity. The primary endpoint is incident T2D (fasting glucose ≥126 mg/dL, or HbA1c ≥6.5%). We will also measure a range of implementation-related process outcomes at the clinic-, clinician- and patient-levels to inform interpretations of effectiveness and enable efforts to refine, adapt, adopt and disseminate the model. We will also estimate the cost-effectiveness of metformin as an adjunct to lifestyle counseling in Mexico.DiscussionFindings from this pragmatic trial will generate new translational knowledge in Mexico and beyond, both with respect to metformin's real-world effectiveness among an 'at-risk' population, and uncovering facilitators and barriers to the reach, adoption and implementation of metformin preventive therapy in public primary care settings.Trial registrationThis trial is registered at Clinicaltrials.gov (NCT03194009).
Published: 2020

5. Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Author: Nalls, Mike A, Blauwendraat, Cornelis, Vallerga, Costanza L, Heilbron, Karl, Bandres-Ciga, Sara, Chang, Diana, Tan, Manuela, Kia, Demis A, Noyce, Alastair J, Xue, Angli, Bras, Jose, Young, Emily, von Coelln, Rainer, Simón-Sánchez, Javier, Schulte, Claudia, Sharma, Manu, Krohn, Lynne, Pihlstrøm, Lasse, Siitonen, Ari, Iwaki, Hirotaka, Leonard, Hampton, Faghri, Faraz, Gibbs, J Raphael, Hernandez, Dena G, Scholz, Sonja W, Botia, Juan A, Martinez, Maria, Corvol, Jean-Christophe, Lesage, Suzanne, Jankovic, Joseph, Shulman, Lisa M, Sutherland, Margaret, Tienari, Pentti, Majamaa, Kari, Toft, Mathias, Andreassen, Ole A, Bangale, Tushar, Brice, Alexis, Yang, Jian, Gan-Or, Ziv, Gasser, Thomas, Heutink, Peter, Shulman, Joshua M, Wood, Nicholas W, Hinds, David A, Hardy, John A, Morris, Huw R, Gratten, Jacob, Visscher, Peter M, Graham, Robert R, Singleton, Andrew B, Team, 23andMe Research, Consortium, System Genomics of Parkinson's Disease, Consortium, International Parkinson's Disease Genomics, Adarmes-Gómez, Astrid D, Aguilar, Miquel, Aitkulova, Akbota, Akhmetzhanov, Vadim, Alcalay, Roy N, Alvarez, Ignacio, Alvarez, Victoria, Barrero, Francisco Javier, Yarza, Jesús Alberto Bergareche, Bernal-Bernal, Inmaculada, Billingsley, Kimberley, Blazquez, Marta, Bonilla-Toribio, Marta, Botía, Juan A, Boungiorno, María Teresa, Brockmann, Kathrin, Bubb, Vivien, Buiza-Rueda, Dolores, Cámara, Ana, Carrillo, Fátima, Carrión-Claro, Mario, Cerdan, Debora, Chelban, Viorica, Clarimón, Jordi, Clarke, Carl, Compta, Yaroslau, Cookson, Mark R, Craig, David W, Danjou, Fabrice, Diez-Fairen, Monica, Dols-Icardo, Oriol, Duarte, Jacinto, Duran, Raquel, Escamilla-Sevilla, Francisco, Escott-Price, Valentina, Ezquerra, Mario, Feliz, Cici, Fernández, Manel, Fernández-Santiago, Rubén, and Finkbeiner, Steven
Subjects: Neurosciences, Parkinson's Disease, Brain Disorders, Aging, Biotechnology, Prevention, Genetics, Human Genome, Neurodegenerative, 2.1 Biological and endogenous factors, Aetiology, Neurological, Databases, Genetic, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Parkinson Disease, Risk Factors, 23andMe Research Team, System Genomics of Parkinson's Disease Consortium, International Parkinson's Disease Genomics Consortium, Clinical Sciences, Neurology & Neurosurgery
Abstract: BackgroundGenome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease.MethodsWe did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation.FindingsBetween Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16-36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10-7).InterpretationThese data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data.FundingThe National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources).
Published: 2019

6. miR-873-5p targets mitochondrial GNMT-Complex II interface contributing to non-alcoholic fatty liver disease

Author: Fernández-Tussy, Pablo, Fernández-Ramos, David, Lopitz-Otsoa, Fernando, Simón, Jorge, Barbier-Torres, Lucía, Gomez-Santos, Beatriz, Nuñez-Garcia, Maitane, Azkargorta, Mikel, Juan, Virginia Gutiérrez-de, Serrano-Macia, Marina, Rodríguez-Agudo, Rubén, Iruzubieta, Paula, Anguita, Juan, Castro, Rui E, Champagne, Devin, Rincón, Mercedes, Elortza, Felix, Arslanow, Anita, Krawczyk, Marcin, Lammert, Frank, Kirchmeyer, Mélanie, Behrmann, Iris, Crespo, Javier, Lu, Shelly C, Mato, José M, Varela-Rey, Marta, Aspichueta, Patricia, Delgado, Teresa C, and Martínez-Chantar, María L
Subjects: Liver Disease, Biotechnology, Hepatitis, Digestive Diseases, Complementary and Integrative Health, Chronic Liver Disease and Cirrhosis, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Metabolic and endocrine, Good Health and Well Being, Adult, Animals, Antagomirs, Disease Models, Animal, Electron Transport Complex II, Female, Glycine N-Methyltransferase, Hepatocytes, Humans, Lipid Peroxidation, Liver, Male, Mice, Mice, Inbred C57BL, MicroRNAs, Middle Aged, Mitochondria, Non-alcoholic Fatty Liver Disease, Up-Regulation, NASH, GNMT, beta-oxidation, Metabolism, microRNA, β-oxidation, Biochemistry and Cell Biology, Physiology
Abstract: OBJECTIVE:Non-alcoholic fatty liver disease (NAFLD) is a complex pathology in which several dysfunctions, including alterations in metabolic pathways, mitochondrial functionality and unbalanced lipid import/export, lead to lipid accumulation and progression to inflammation and fibrosis. The enzyme glycine N-methyltransferase (GNMT), the most important enzyme implicated in S-adenosylmethionine catabolism in the liver, is downregulated during NAFLD progression. We have studied the mechanism involved in GNMT downregulation by its repressor microRNA miR-873-5p and the metabolic pathways affected in NAFLD as well as the benefit of recovery GNMT expression. METHODS:miR-873-5p and GNMT expression were evaluated in liver biopsies of NAFLD/NASH patients. Different in vitro and in vivo NAFLD murine models were used to assess miR-873-5p/GNMT involvement in fatty liver progression through targeting of the miR-873-5p as NAFLD therapy. RESULTS:We describe a new function of GNMT as an essential regulator of Complex II activity in the electron transport chain in the mitochondria. In NAFLD, GNMT expression is controlled by miR-873-5p in the hepatocytes, leading to disruptions in mitochondrial functionality in a preclinical murine non-alcoholic steatohepatitis (NASH) model. Upregulation of miR-873-5p is shown in the liver of NAFLD/NASH patients, correlating with hepatic GNMT depletion. Importantly, NASH therapies based on anti-miR-873-5p resolve lipid accumulation, inflammation and fibrosis by enhancing fatty acid β-oxidation in the mitochondria. Therefore, miR-873-5p inhibitor emerges as a potential tool for NASH treatment. CONCLUSION:GNMT participates in the regulation of metabolic pathways and mitochondrial functionality through the regulation of Complex II activity in the electron transport chain. In NAFLD, GNMT is repressed by miR-873-5p and its targeting arises as a valuable therapeutic option for treatment.
Published: 2019

7. Collaborative research and actions on both sides of the US-Mexico border to counteract type 2 diabetes in people of Mexican origin

Author: Barquera, Simón, Schillinger, Dean, Aguilar-Salinas, Carlos A, Schenker, Marc, Rodríguez, Luis A, Hernández-Alcaraz, Cesar, Sepúlveda-Amor, Jaime, and Mexico-California Diabetes collaborative group
Subjects: Health Services and Systems, Public Health, Health Sciences, Clinical Research, Diabetes, Health Services, Prevention, Nutrition, Metabolic and endocrine, Good Health and Well Being, California, Diabetes Mellitus, Type 2, Health Surveys, Humans, Incidence, International Cooperation, Mexican Americans, Mexico, Risk, Translational Research, Biomedical, United States, Global Health, Translational Research, Health Policy, Mexico-California Diabetes collaborative group, California, Mexico, Diabetes, Prevention, Global Health, Translational Research, Health Policy, Public Health and Health Services, General & Internal Medicine, Health services and systems, Public health, Policy and administration
Abstract: BackgroundType 2 Diabetes (T2D) is now a massive epidemic in both California and Mexico, with serious consequences for social and economic well-being. A large proportion of these populations share common ethnic backgrounds. Yet diverse environmental and social conditions across regions create unique opportunities to explore the ways that T2D risk, incidence, management and outcomes manifest.Main textAn action-oriented research consortium headed up by the University of California and Universidad Nacional Autónoma de Mexico was constituted to set priorities for bi-national translational research, in an attempt to implement and evaluate clinical, public health and policy actions to decrease the burden of T2D for people of Mexican origin. In this paper, we describe the epidemiology of T2D in Mexico and California, review current efforts to combat the epidemic, highlight gaps in knowledge and identify urgent areas of opportunity for collaboration. The group has developed a common research agenda and funding has been obtained to evaluate biological samples from the 2016 Mexican Health Survey, collaborate in a telemedicine-based retinopathy project, implement interventions in food banks, promote a communications campaign, and design a large-scale diabetes prevention effectiveness trial.ConclusionsT2D has caused a state of emergency in Mexico and is a major health problem among Mexican populations on both sides of the border. Understanding the commonalities and differences between California and Mexico for those of Mexican origin with respect to T2D, when combined with a sharing of knowledge and advances, can produce a bi-national translational research agenda to inform relevant policy and practice. Amidst economic and political uncertainty and limited healthcare budgets, this collaboration can contribute to the development of scientific evidence to inform policies and interventions. This may provide a promising collaborative model that could be expanded to other health conditions and regions of the world.
Published: 2018

8. MiR-873-5p acts as an epigenetic regulator in early stages of liver fibrosis and cirrhosis.

Author: Fernández-Ramos, David, Fernández-Tussy, Pablo, Lopitz-Otsoa, Fernando, Gutiérrez-de-Juan, Virginia, Navasa, Nicolás, Barbier-Torres, Lucía, Zubiete-Franco, Imanol, Simón, Jorge, Fernández, Agustín F, Arbelaiz, Ander, Aransay, Ana M, Lavín, José Luis, Beraza, Naiara, Perugorria, María J, Banales, Jesus M, Villa, Erica, Fraga, Mario F, Anguita, Juan, Avila, Matias A, Berasain, Carmen, Iruzibieta, Paula, Crespo, Javier, Lu, Shelly C, Varela-Rey, Marta, Mato, José M, Delgado, Teresa C, and Martínez-Chantar, María L
Subjects: Liver, Animals, Mice, Inbred C57BL, Humans, Mice, Carcinoma, Hepatocellular, Liver Cirrhosis, Fibrosis, MicroRNAs, Cell Proliferation, Male, Glycine N-Methyltransferase, Hepatic Stellate Cells, Inbred C57BL, Carcinoma, Hepatocellular, Biochemistry and Cell Biology, Oncology and Carcinogenesis
Abstract: Glycine N-methyltransferase (GNMT) is the most abundant methyltransferase in the liver and a master regulator of the transmethylation flux. GNMT downregulation leads to loss of liver function progressing to fibrosis, cirrhosis, and hepatocellular carcinoma. Moreover, GNMT deficiency aggravates cholestasis-induced fibrogenesis. To date, little is known about the mechanisms underlying downregulation of GNMT levels in hepatic fibrosis and cirrhosis. On this basis, microRNAs are epigenetic regulatory elements that play important roles in liver pathology. In this work, we aim to study the regulation of GNMT by microRNAs during liver fibrosis and cirrhosis. Luciferase assay on the 3'UTR-Gnmt was used to confirm in silico analysis showing that GNMT is potentially targeted by the microRNA miR-873-5p. Correlation between GNMT and miR-873-5p in human cholestasis and cirrhosis together with miR-873-5p inhibition in vivo in different mouse models of liver cholestasis and fibrosis [bile duct ligation and Mdr2 (Abcb4)-/- mouse] were then assessed. The analysis of liver tissue from cirrhotic and cholestatic patients, as well as from the animal models, showed that miR-873-5p inversely correlated with the expression of GNMT. Importantly, high circulating miR-873-5p was also detected in cholestastic and cirrhotic patients. Preclinical studies with anti-miR-873-5p treatment in bile duct ligation and Mdr2-/- mice recovered GNMT levels in association with ameliorated inflammation and fibrosis mainly by counteracting hepatocyte apoptosis and cholangiocyte proliferation. In conclusion, miR-873-5p emerges as a novel marker for liver fibrosis, cholestasis, and cirrhosis and therapeutic approaches based on anti-miR-873-5p may be effective treatments for liver fibrosis and cholestatic liver disease.
Published: 2018

9. Competition of charge-mediated and specific binding by peptide-tagged cationic liposome–DNA nanoparticles in vitro and in vivo

Author: Wonder, Emily, Simón-Gracia, Lorena, Scodeller, Pablo, Majzoub, Ramsey N, Kotamraju, Venkata Ramana, Ewert, Kai K, Teesalu, Tambet, and Safinya, Cyrus R
Subjects: Medical Biotechnology, Biological Sciences, Biomedical and Clinical Sciences, Industrial Biotechnology, Nanotechnology, Bioengineering, Cancer, Animals, Antineoplastic Agents, Cations, DNA, Gene Transfer Techniques, Genetic Therapy, Humans, Lipids, Liposomes, Nanoparticles, Peptides, Cationic liposome-DNA nanoparticles, Tumor-penetrating peptides, iRGD, Cyclic RGD, C-end rule
Abstract: Cationic liposome-nucleic acid (CL-NA) complexes, which form spontaneously, are a highly modular gene delivery system. These complexes can be sterically stabilized via PEGylation [PEG: poly (ethylene glycol)] into nanoparticles (NPs) and targeted to specific tissues and cell types via the conjugation of an affinity ligand. However, there are currently no guidelines on how to effectively navigate the large space of compositional parameters that modulate the specific and nonspecific binding interactions of peptide-targeted NPs with cells. Such guidelines are desirable to accelerate the optimization of formulations with novel peptides. Using PEG-lipids functionalized with a library of prototypical tumor-homing peptides, we varied the peptide density and other parameters (binding motif, peptide charge, CL/DNA charge ratio) to study their effect on the binding and uptake of the corresponding NPs. We used flow cytometry to quantitatively assess binding as well as internalization of NPs by cultured cancer cells. Surprisingly, full peptide coverage resulted in less binding and internalization than intermediate coverage, with the optimum coverage varying between cell lines. In, addition, our data revealed that great care must be taken to prevent nonspecific electrostatic interactions from interfering with the desired specific binding and internalization. Importantly, such considerations must take into account the charge of the peptide ligand as well as the membrane charge density and the CL/DNA charge ratio. To test our guidelines, we evaluated the in vivo tumor selectivity of selected NP formulations in a mouse model of peritoneally disseminated human gastric cancer. Intraperitoneally administered peptide-tagged CL-DNA NPs showed tumor binding, minimal accumulation in healthy control tissues, and preferential penetration of smaller tumor nodules, a highly clinically relevant target known to drive recurrence of the peritoneal cancer.
Published: 2018

10. Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology

Author: Garrido-Gomez, Tamara, Dominguez, Francisco, Quiñonero, Alicia, Diaz-Gimeno, Patricia, Kapidzic, Mirhan, Gormley, Matthew, Ona, Katherine, Padilla-Iserte, Pablo, McMaster, Michael, Genbacev, Olga, Perales, Alfredo, Fisher, Susan J, and Simón, Carlos
Subjects: Reproductive Medicine, Biomedical and Clinical Sciences, Contraception/Reproduction, Pediatric, Cardiovascular, Perinatal Period - Conditions Originating in Perinatal Period, Hypertension, Biotechnology, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Good Health and Well Being, Adult, Cells, Cultured, Decidua, Embryo Implantation, Endometrium, Female, Gene Expression Profiling, Gene Expression Regulation, Humans, Pre-Eclampsia, Pregnancy, Pregnancy Trimester, First, Stromal Cells, Trophoblasts, preeclampsia, human endometrial stromal cells, decidua, cytotrophoblast, transcriptomics
Abstract: In preeclampsia (PE), cytotrophoblast (CTB) invasion of the uterus and spiral arteries is often shallow. Thus, the placenta's role has been a focus. In this study, we tested the hypothesis that decidual defects are an important determinant of the placental phenotype. We isolated human endometrial stromal cells from nonpregnant donors with a previous pregnancy that was complicated by severe PE (sPE). Compared with control cells, they failed to decidualize in vitro as demonstrated by morphological criteria and the analysis of stage-specific antigens (i.e., IGFBP1, PRL). These results were bolstered by global transcriptional profiling data that showed they were transcriptionally inert. Additionally, we used laser microdissection to isolate the decidua from tissue sections of the maternal-fetal interface in sPE. Global transcriptional profiling revealed defects in gene expression. Also, decidual cells from patients with sPE, which dedifferentiated in vitro, failed to redecidualize in culture. Conditioned medium from these cells failed to support CTB invasion. To mimic aspects of the uterine environment in normal pregnancy, we added PRL and IGFBP1, which enhanced invasion. These data suggested that failed decidualization is an important contributor to down-regulated CTB invasion in sPE. Future studies will be aimed at determining whether this discovery has translational potential with regard to assessing a woman's risk of developing this pregnancy complication.
Published: 2017

11. Meta-signature of human endometrial receptivity: a meta-analysis and validation study of transcriptomic biomarkers.

Author: Altmäe, Signe, Koel, Mariann, Võsa, Urmo, Adler, Priit, Suhorutšenko, Marina, Laisk-Podar, Triin, Kukushkina, Viktorija, Saare, Merli, Velthut-Meikas, Agne, Krjutškov, Kaarel, Aghajanova, Lusine, Lalitkumar, Parameswaran G, Gemzell-Danielsson, Kristina, Giudice, Linda, Simón, Carlos, and Salumets, Andres
Subjects: Endometrium, Humans, MicroRNAs, RNA, Messenger, Gene Expression Profiling, Sequence Analysis, RNA, Computational Biology, Embryo Implantation, Fertility, Menstrual Cycle, Adult, Female, Gene Regulatory Networks, Immunity, Innate, Exosomes, Molecular Sequence Annotation, Transcriptome, Gene Ontology, Biomarkers, RNA, Messenger, Sequence Analysis, Immunity, Innate, Biotechnology, Genetics, Human Genome, Uterine Cancer, Contraception/Reproduction, Cancer, Infertility, 4.1 Discovery and preclinical testing of markers and technologies, Biochemistry and Cell Biology, Other Physical Sciences
Abstract: Previous transcriptome studies of the human endometrium have revealed hundreds of simultaneously up- and down-regulated genes that are involved in endometrial receptivity. However, the overlap between the studies is relatively small, and we are still searching for potential diagnostic biomarkers. Here we perform a meta-analysis of endometrial-receptivity associated genes on 164 endometrial samples (76 from 'pre-receptive' and 88 from mid-secretory, 'receptive' phase endometria) using a robust rank aggregation (RRA) method, followed by enrichment analysis, and regulatory microRNA prediction. We identify a meta-signature of endometrial receptivity involving 57 mRNA genes as putative receptivity markers, where 39 of these we confirm experimentally using RNA-sequencing method in two separate datasets. The meta-signature genes highlight the importance of immune responses, the complement cascade pathway and the involvement of exosomes in mid-secretory endometrial functions. Bioinformatic prediction identifies 348 microRNAs that could regulate 30 endometrial-receptivity associated genes, and we confirm experimentally the decreased expression of 19 microRNAs with 11 corresponding up-regulated meta-signature genes in our validation experiments. The 57 identified meta-signature genes and involved pathways, together with their regulatory microRNAs could serve as promising and sought-after biomarkers of endometrial receptivity, fertility and infertility.
Published: 2017

12. What Does It Mean to Successfully Conserve a (Vertebrate) Species?

Author: Redford, Kent H., Amato, George, Baillie, Jonathan, Beldomenico, Pablo, Bennett, Elizabeth L., Clum, Nancy, Cook, Robert, Fonseca, Gustavo, Hedges, Simon, Launay, Frederic, Lieberman, Susan, Mace, Georgina M., Murayama, Akira, Putnam, Andrea, Robinson, John G., Rosenbaum, Howard, Sanderson, Eric W., Stuart, Simon N., Thomas, Patrick, and Thorbjarnarson, John
Published: 2011
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13. Projected Impact of Mexico's Sugar-Sweetened Beverage Tax Policy on Diabetes and Cardiovascular Disease: A Modeling Study.

Author: Sánchez-Romero, Luz Maria, Penko, Joanne, Coxson, Pamela G, Fernández, Alicia, Mason, Antoinette, Moran, Andrew E, Ávila-Burgos, Leticia, Odden, Michelle, Barquera, Simón, and Bibbins-Domingo, Kirsten
Subjects: Humans, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Dietary Sucrose, Sweetening Agents, Incidence, Prevalence, Risk Factors, Models, Theoretical, Beverages, Computer Simulation, Adult, Aged, Aged, 80 and over, Middle Aged, Health Care Costs, Taxes, Mexico, Female, Male, Clinical Research, Heart Disease, Prevention, Cardiovascular, Nutrition, Metabolic and endocrine, Good Health and Well Being, Medical and Health Sciences, General & Internal Medicine
Abstract: BackgroundRates of diabetes in Mexico are among the highest worldwide. In 2014, Mexico instituted a nationwide tax on sugar-sweetened beverages (SSBs) in order to reduce the high level of SSB consumption, a preventable cause of diabetes and cardiovascular disease (CVD). We used an established computer simulation model of CVD and country-specific data on demographics, epidemiology, SSB consumption, and short-term changes in consumption following the SSB tax in order to project potential long-range health and economic impacts of SSB taxation in Mexico.Methods and findingsWe used the Cardiovascular Disease Policy Model-Mexico, a state transition model of Mexican adults aged 35-94 y, to project the potential future effects of reduced SSB intake on diabetes incidence, CVD events, direct diabetes healthcare costs, and mortality over 10 y. Model inputs included short-term changes in SSB consumption in response to taxation (price elasticity) and data from government and market research surveys and public healthcare institutions. Two main scenarios were modeled: a 10% reduction in SSB consumption (corresponding to the reduction observed after tax implementation) and a 20% reduction in SSB consumption (possible with increases in taxation levels and/or additional measures to curb consumption). Given uncertainty about the degree to which Mexicans will replace calories from SSBs with calories from other sources, we evaluated a range of values for calorie compensation. We projected that a 10% reduction in SSB consumption with 39% calorie compensation among Mexican adults would result in about 189,300 (95% uncertainty interval [UI] 155,400-218,100) fewer incident type 2 diabetes cases, 20,400 fewer incident strokes and myocardial infarctions, and 18,900 fewer deaths occurring from 2013 to 2022. This scenario predicts that the SSB tax could save Mexico 983 million international dollars (95% UI $769 million-$1,173 million). The largest relative and absolute reductions in diabetes and CVD events occurred in the youngest age group modeled (35-44 y). This study's strengths include the use of an established mathematical model of CVD and use of contemporary Mexican vital statistics, data from health surveys, healthcare costs, and SSB price elasticity estimates as well as probabilistic and deterministic sensitivity analyses to account for uncertainty. The limitations of the study include reliance on US-based studies for certain inputs where Mexico-specific data were lacking (specifically the associations between risk factors and CVD outcomes [from the Framingham Heart Study] and SSB calorie compensation assumptions), limited data on healthcare costs other than those related to diabetes, and lack of information on long-term SSB price elasticity that is specific to geographic and economic subgroups.ConclusionsMexico's high diabetes prevalence represents a public health crisis. While the long-term impact of Mexico's SSB tax is not yet known, these projections, based on observed consumption reductions, suggest that Mexico's SSB tax may substantially decrease morbidity and mortality from diabetes and CVD while reducing healthcare costs.
Published: 2016

14. Paclitaxel-Loaded Cationic Fluid Lipid Nanodiscs and Liposomes with Brush-Conformation PEG Chains Penetrate Breast Tumors and Trigger Caspase-3 Activation

Author: Lorena Simón-Gracia, Pablo Scodeller, William S. Fisher, Valeria Sidorenko, Victoria M. Steffes, Kai K. Ewert, Cyrus R. Safinya, Tambet Teesalu, National Institutes of Health (US), European Commission, Estonian Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), National Science Foundation (US), Simón-Gracia, Lorena [0000-0003-1825-8723], Scodeller, Pablo David [0000-0003-0745-2467], Sidorenko, Valeria [0000-0001-9932-1258], Ewert, Kai K. [0000-0002-4861-8278], Safinya, Cyrus R. [0000-0002-3295-7128], Teesalu, Tambet [0000-0002-9458-6385], Simón-Gracia, Lorena, Scodeller, Pablo David, Sidorenko, Valeria, Ewert, Kai K., Safinya, Cyrus R., and Teesalu, Tambet
Subjects: Drug Carriers, Tumor Penetration, Paclitaxel, Caspase 3, PEGylation, Triple-Negative Breast Cancer, Breast Neoplasms, Lipids, Antineoplastic Agents, Phytogenic, Polyethylene Glycols, Fluid Lipid Disc Bicelle, Mice, Cell Line, Tumor, Liposomes, Cationic Liposome, Humans, Animals, Chemotherapy, Female, Tissue Distribution, General Materials Science
Abstract: Novel approaches are required to address the urgent need to develop lipid-based carriers of paclitaxel (PTX) and other hydrophobic drugs for cancer chemotherapy. Carriers based on cationic liposomes (CLs) with fluid (i.e., chain-melted) membranes (e.g., EndoTAG-1®) have shown promise in preclinical and late-stage clinical studies. Recent work found that the addition of a cone-shaped poly(ethylene glycol)-lipid (PEG-lipid) to PTX-loaded CLs (CLsPTX) promotes a transition to sterically stabilized, higher-curvature (smaller) nanoparticles consisting of a mixture of PEGylated CLsPTX and PTX-containing fluid lipid nanodiscs (nanodiscsPTX). These CLsPTX and nanodiscsPTX show significantly improved uptake and cytotoxicity in cultured human cancer cells at PEG coverage in the brush regime (10 mol% PEG-lipid). Here, we studied the PTX loading, in vivo circulation half-life, and biodistribution of systemically administered CLsPTX and nanodiscsPTX and assessed their ability to induce apoptosis in triple-negative breast cancer-bearing immunocompetent mice. We focused on fluid rather than solid lipid nanodiscs because of the significantly higher solubility of PTX in fluid membranes. At 5 and 10 mol% of a PEG-lipid (PEG5K-lipid, molecular weight of PEG 5000 g/mol), the mixture of PEGylated CLsPTX and nanodiscsPTX was able to incorporate up to 2.5 mol% PTX without crystallization for at least 20 h. Remarkably, compared to preparations containing 2 and 5 mol% PEG5K-lipid (with the PEG chains in the mushroom regime), the particles at 10 mol% (with PEG chains in the brush regime) showed significantly higher blood half-life, tumor penetration and proapoptotic activity. Our study suggests that increasing the PEG coverage of CL-based drug nanoformulations can improve their pharmacokinetics and therapeutic efficacy., This research study was supported by the National Institutes of Health under award R01GM130769 (CRS, KKE, WF; mechanistic studies on developing lipid nanoparticles for drug delivery), the European Regional Development Fund (TT, Project No. 2014-2020.4.01.15-0012), the Estonian Research Council (TT, grants PRG230 and EAG79; PS, grant PSG38; LSG, grant MOBJD11), EuronanomedII projects ECM-CART and iNanoGun (TT), H2020 MSCA-RISE project Oxigenated (TT), and the Spanish Ministry of Science and Innovation grants RYC2020-028754-I and PID2021-122364OA-I00 (PS). Partial support was provided by the US National Science Foundation (NSF) under Award DMR-1807327 (CRS; kinetic phase behavior of cationic vesicles with incorporated hydrophobic molecules).
Published: 2022
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15. Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification.

Author: Zdravkovic, Tamara, Nazor, Kristopher L, Larocque, Nicholas, Gormley, Matthew, Donne, Matthew, Hunkapillar, Nathan, Giritharan, Gnanaratnam, Bernstein, Harold S, Wei, Grace, Hebrok, Matthias, Zeng, Xianmin, Genbacev, Olga, Mattis, Aras, McMaster, Michael T, Krtolica, Ana, Valbuena, Diana, Simón, Carlos, Laurent, Louise C, Loring, Jeanne F, and Fisher, Susan J
Subjects: Blastomeres, Cell Line, Fibroblasts, Myocytes, Cardiac, Trophoblasts, Blastocyst, Endoderm, Humans, Oligonucleotide Array Sequence Analysis, Embryo Culture Techniques, Gene Expression Profiling, Cell Differentiation, DNA Methylation, Transcription, Genetic, Gene Expression Regulation, Developmental, Cell Lineage, beta Catenin, Embryonic Stem Cells, Growth Differentiation Factor 15, Neural Stem Cells, Transcriptome, Blastomere, Epigenome, Fate specification, Human embryo, Human embryonic stem cell, Human trophoblast stem cell, Stem Cell Research, Stem Cell Research - Nonembryonic - Non-Human, Genetics, 1.1 Normal biological development and functioning, Generic health relevance, Biological Sciences, Medical and Health Sciences
Abstract: Mechanisms of initial cell fate decisions differ among species. To gain insights into lineage allocation in humans, we derived ten human embryonic stem cell lines (designated UCSFB1-10) from single blastomeres of four 8-cell embryos and one 12-cell embryo from a single couple. Compared with numerous conventional lines from blastocysts, they had unique gene expression and DNA methylation patterns that were, in part, indicative of trophoblast competence. At a transcriptional level, UCSFB lines from different embryos were often more closely related than those from the same embryo. As predicted by the transcriptomic data, immunolocalization of EOMES, T brachyury, GDF15 and active β-catenin revealed differential expression among blastomeres of 8- to 10-cell human embryos. The UCSFB lines formed derivatives of the three germ layers and CDX2-positive progeny, from which we derived the first human trophoblast stem cell line. Our data suggest heterogeneity among early-stage blastomeres and that the UCSFB lines have unique properties, indicative of a more immature state than conventional lines.
Published: 2015

16. Guidelines for the design, analysis and interpretation of ‘omics’ data: focus on human endometrium

Author: Altmäe, Signe, Esteban, Francisco J, Stavreus-Evers, Anneli, Simón, Carlos, Giudice, Linda, Lessey, Bruce A, Horcajadas, Jose A, Macklon, Nick S, D'Hooghe, Thomas, Campoy, Cristina, Fauser, Bart C, Salamonsen, Lois A, and Salumets, Andres
Subjects: Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Genetics, Biotechnology, Human Genome, Generic health relevance, Embryo Implantation, Endometrium, Female, Genomics, Guidelines as Topic, High-Throughput Nucleotide Sequencing, Humans, Metabolomics, Systems Biology, endometrium, epigenomics, genomics, metabolomics, proteomics, Clinical Sciences, Paediatrics and Reproductive Medicine, Public Health and Health Services, Obstetrics & Reproductive Medicine, Reproductive medicine
Abstract: Background'Omics' high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies. Analysis of endometrial transcriptome patterns in physiological and pathophysiological conditions has been to date the most commonly applied 'omics' technique in human endometrium. As the technologies improve, proteomics holds the next big promise for this field. The 'omics' technologies have undoubtedly advanced our knowledge of human endometrium in relation to fertility and different diseases. Nevertheless, the challenges arising from the vast amount of data generated and the broad variation of 'omics' profiling according to different environments and stimuli make it difficult to assess the validity, reproducibility and interpretation of such 'omics' data. With the expansion of 'omics' analyses in the study of the endometrium, there is a growing need to develop guidelines for the design of studies, and the analysis and interpretation of 'omics' data.MethodsSystematic review of the literature in PubMed, and references from relevant articles were investigated up to March 2013.ResultsThe current review aims to provide guidelines for future 'omics' studies on human endometrium, together with a summary of the status and trends, promise and shortcomings in the high-throughput technologies. In addition, the approaches presented here can be adapted to other areas of high-throughput 'omics' studies.ConclusionA highly rigorous approach to future studies, based on the guidelines provided here, is a prerequisite for obtaining data on biological systems which can be shared among researchers worldwide and will ultimately be of clinical benefit.
Published: 2014

17. Effects of hospital facilities on patient outcomes after cancer surgery

Author: Knight, Sr, Chu, K, Lapitan, Mc, Dare, Aj, Pius, R, Shaw, Ca, Drake, Tm, Norman, L, Ademuyiwa, Ao, Adisa, Ao, Aguilera, Ml, Al-Saqqa, Sw, Al-Slaibi, I, Bhangu, A, Biccard, Bm, Brocklehurst, P, Costas-Chavarri, A, Elhadi, M, Fairfield, Cj, Fitzgerald, Je, Ghosh, D, Glasbey, J, Henegouwen, Miv, Ingabire, Jca, Kingham, Tp, Lawani, I, Lieske, B, Lilford, R, Martin, J, Mclean, Ka, Moore, R, Morton, D, Nepogodiev, D, Ntirenganya, F, Pata, F, Pinkney, T, Stephen, R Knight, Catherine, A Shaw, Riinu, Pius, Thomas, M Drake, Lisa, Norman, Adesoji, O Ademuyiwa, Adewale, O Adisa, Maria Lorena Aguilera, Sara, W Al-Saqqa, Ibrahim, Al-Slaibi, Aneel, Bhangu, Bruce, M Biccard, Peter, Brocklehurst, Ainhoa, Costas-Chavarri, Kathryn, Chu, Anna, Dare, Muhammed, Elhadi, Cameron, J Fairfield, J Edward Fitzgerald, Dhruv, Ghosh, James, Glasbey, Mark, I van Berge Henegouwen, C Allen Ingabire, J, T Peter Kingham, Marie Carmela Lapitan, Ismaïl, Lawani, Bettina, Lieske, Richard, Lilford, Janet, Martin, Kenneth, A McLean, Rachel, Moore, Dion, Morton, Dmitri, Nepogodiev, Faustin, Ntirenganya, Francesco, Pata, Thomas, Pinkney, Ahmad Uzair Qureshi, Antonio Ramos-De la Medina, Aya, Riad, Hosni Khairy Salem, Joana, Simões, Richard, Spence, Neil, Smart, Stephen, Tabiri, Hannah, Thomas, Thomas, G Weiser, Malcolm, West, John, Whitaker, Ewen, M Harrison, Arben, Gjata, Maria Marta Modolo, Sebastian, King, Erick, Chan, Sayeda Nazmun Nahar, Ade, Waterman, Dominique, Vervoort, Alemayehu Ginbo Bedada, Bernardo De Azevedo, Ana Gabriela Figueiredo, Manol, Sokolov, Venerand, Barendegere, Gerald, Ekwen, Arnav, Agarwal, Qinyang, Liu, Juan Camilo Correa, Kalisya Luc Malemo, Jacques, Bake, Jakov, Mihanovic, Kamila, Kunčarová, Julius, Orhalmi, Hosni, Salem, Jyri, Teras, Aristotelis, Kechagias, Alexis, P Arnaud, Judith, Lindert, Vasileios, Kalles, Maria-Lorena, Aguilera-Arevalo, Gustavo, Recinos, Zsolt, Baranyai, Basant, Kumar, Harish Neelamraju Lakshmi, Sanoop Koshy Zachariah, Philip, Alexander, Sunil Kumar Venkatappa, Pramesh, C, Radhian, Amandito, Christina, Fleming, Luca, Ansaloni, Gianluca, Pellino, Ahmed, M Altibi, Ibrahim, Nour, Intisar, Hamdun, Ali, M Ghellai, Donatas, Venskutonis, Tomas, Poskus, Justas, Zilinskas, Precious, Malemia, Yong Yong Tew, Elaine, Borg, Sarah, Ellul, Fatima Zahraa Wafqui, David, W Borowski, Anne Sophie van Dalen, Cameron, Wells, Harissou, Adamou, Adesoji, Ademuyiwa, Adewale, Adisa, Kjetil, Søreide, Sara Al Saqqa, Osaid, Alser, Haya, Tahboub, Helmut Alfredo Segovia Lohse, Sebastian Shu Yip, Piotr, Major, António Sampaio Soares, Matei Razvan Bratu, Andrey, Litvin, Armen, Vardanyan, Ahmad, Gudal, Naif, Albati, Jovan, Juloski, Miran, Rems, Sarah, Rayne, Stephanie Van Straten, Yoshan, Moodley, Irene Ortega Vázquez, Jaime, Ruiz-Tovar, Kithsiri Janakantha Senanayake, Sujeewa Priyantha Bandara Thalgaspitiya, Omer Abdelbagi Omer, Anmar, Homeida, Yucel, Cengiz, Daniel, Clerc, Muhammad, Alshaar, Hanen, Bouaziz, Yuksel, Altinel, Matthew, Doe, Maryna, Freigofer, Ella, Teasdale, Rakan, Kabariti, Joshua Michael Clements, Stephen Richard Knight, Ahsan, Ashfaq, Ijeoma, Azodo, Gabriela, Wagner, Ivan, Trostchansky, Mayaba, Maimbo, David, Linyama, Helidon, Nina, Amanda, Zeko, Claudio Gabriel Fermani, Santiago, Villalobos, Federico, Carballo, Pablo, Farina, Sebastian, Guckenheimer, Marilla, Dickfos, Ankit, Ajmera, Chester, Chong, Ralph, Gourlay, Sikandar, Hussaini, Yi Jia Lee, Adeeb, Majid, Peter, Martin, Rebecca, Miles, Owen James Morris, Jamie, Phua, William, Ridley, Tarunpreet, Saluja, Ryan Renxin Tan, Jen, Teh, Anna, Wells, Bharti, Arora, Qaasim, Dollie, Debbie, Ho, Yanru, Ma, Omattage Mahasha Perera, Anthony, Truong, Amanda Caroline Dawson, Bryan, Lim, Upuli, Pahalawatta, Jacqueline, Phan, Xiao-Ming Sarah Woon-Shoo-Tong, Andrea, Yeoh, Lillian, Charman, Andrew, Drane, Sharon, Laura, Charmaine Chu Wen Lo, Amy, Mozes, Rita, Poon, Hao Han Tan, Ellen, Wall, Prakshi, Chopra, Jasmine De Giovanni, Bal, Dhital, Brian, Draganic, Alexander, Duller, Jonathan, Gani, Yao Kuan Goh, Jun Young Jeong, Brendan, Mcmanus, Prakash, Nagappan, Peter, Pockney, Anya, Rugendyke, Mahsa, Sarrami, Stephen, Smith, Vanessa, Wills, Hsu Ven Wong, Geoffrey, Ye, Geoffrey, Zhang, Ethan, Brooker, Daniel, Feng, Bonnie, Lau, Carlin, Ngai, Sarah, Birks, David, Gyorki, Jaime Otero de Pablos, Ali, Abbosh, Chris, Gillespie, Ahmed, Mahmoud, Bianca, Kwan, Joshua, Lawson, Andrea, Warwick, Janne, Bingham, Andrew, J Cockbain, Nagendra Naidu Dudi-Venkata, Jordan, Ellaby-Hall, Ben, Finlay, Emily, Humphries, Jade, Pisaniello, Monique, Pisaniello, Salma, Salih, Tarik, Sammour, Haidar Hadri Abd Wahab, April De Silva, Nicola, Hayward, Kartik, Iyer, Guy, Maddern, Gian Andrea Prevost, Naga, Annapureddy, Krishna Pranathi Settipalli, Jeremy, Yeo, Lucy, Hempenstall, Lily, Pham, Shaun, Purcell, Cherry, Talavera, Ashish, I Vaska, Gurpreet, Chaggar, Phillip, Chrapko, Annelise, Cocco, Sarah Michelle Crystal Jade Coulter-Nile, Grahame, Ctercteko, James, French, Houchen, Gong, Martijn, Gosselink, Thuvarahan, Jegathees, Ivan, Jin, Michelle, Kalachov, Kathryn, Kiefhaber, Katherine, Lee, Jason, Luong, Steven, Phan, Henry, Pleass, Kelly, Veale, Zhi, Zeng, Angela, Au, Ashe, Debiasio, Idy, Deng, Jananee, Myooran, Amrita, Nair, Peter, Stewart, Anton, Stift, Lukas Walter Unger, Kerstin, Wimmer, Nabila, Ahmed, Syed, Hasan, Saber, Rahman, Margaret, O'Shea, Greg, Padmore, Adrian, Peters, Pietro, Perduca, Guenda, Pulcina, Nicolas, Tinton, Frederic, Buxant, Elsa, Dabin, Giulia, Garofalo, Francis, Dossou, Freddy Houehanou Rodrigue Gnangnon, Yacoubou Imorou Souaibou, Pako, Motlaleselelo, Omphile, Tlhomelang, Igor Lima Buarque, Gustavo Mendonça Ataíde Gomes, Aldo Vieira Barros, Ilia, Batashki, Nikolai, Damianov, Vladislav, Stoyanov, Dragomir, Dardanov, Svilen, Maslyankov, Plamen, Petkov, George, Todorov, Evgeni, Zhivkov, Aygulya, Akisheva, Miguel Angel Castilla Moreno, Geno, Genov, Ivelina, Ilieva, Tsvetomir, Ivanov, Martin, Karamanliev, Azhar, Khan, Emil, Mitkov, Tsanko, Yotsov, Boyko, Atanasov, Nikolay, Belev, Mihail, Slavchev, Carlos, Nsengiyumva, Elgan, Jones, Simon, Stock, Steve, Kyota, James, Brown, Tresor Mabanza, K, Lemery Nigo Samuel, Chidi, Otuneme, Ngwang, Prosper, Franklin, Umenze, Marylise, Boutros, Natasha, Caminsky, Sinziana, Dumitra, Richard, Garfinkle, Dominique, Morency, Ebram, Salama, Alexander, Banks, Lorenzo, Ferri, Haitian, He, Amit, Katz, Alexander Sender Liberman, Sarkis, Meterissian, Allison, Pang, Elena, Parvez, Usmaan, Hameed, Fahima, Osman, Sangita, Sequeira, Natalie, Coburn, Alisha, Jaffer, Paul, Karanicolas, Matthew, Mosseler, Reilly, Musselman, Xinyuan, Liu, Ching Wan Yip, Juan Sebastian Garces-Otero, Carolina, Guzman, Sebastian, Sierra, Andres Uribe Valencia, Paulo Andrés Cabrera Rivera, Saul, Camelo, Andrea, Gonzalez, Alejandro, González-Orozco, Manuel Santiago Mosquera Paz, Carlos J- Perez Rivera, Felipe, Gonzalez, Andres, Isaza-Restrepo, Laura, Nino-Torres, Natalia Arias Madrid, Maria Clara Mendoza Arango, Justin, Tsandiraki, Damir, Jemendžić, Branislav, Kocman, Oliver, Šuman, Renata, Canic, Darko, Jurišić, Ivana, Karakas, Ana Krizanovic Rupcic, Vlatka, Pitlovic, Josip, Samardžić, Mario, Kopljar, Ivan, Bacic, Edgar, Domini, Robert, Karlo, Danijela, Miljanić, Andrea, Simic, Mariam, Ahmed, Majdi Al Nassrallah, Rabiya, Altaf, Talal, Amjad, Ruba, Eltoum, Heba, Haidar, Alhassan, Hassan, Omar, Khalil, Marwan, Qasem, Rommel, Ramesh, Gautham, Sajith, Maham, Wisal, Jan, Žatecký, Michele, Bujda, Katerina, Jirankova, Ales, Paclik, Aya, Abdallah, Mariam Abdulgawad Almogy, Esraa Ayman El-Sawy, Ahmed Moustafa ElFayoumy, Nourhan, Elghareeb, Nourhan Ahmed Esmat, Ahmed, Fadel, Abdullah, Habater, Heba, Hamdy, Amr, Hefni, Marwa, Kamal, Norhan Mohamed Abobakr, Ahmed, Sayed, Nancy, Shaker, Ehab, Taha, Hoda, Tharwat, Omar, Zakaria, Ibrahem, Abdelmotaleb, Ali, Al-Dhufri, Hamza, S Al-Himyari, Enas El Sheikh, Asmaa, Eldmaty, Aya, Elkhalawy, Ahmed, M Elkhashen, Kithara, Magdy, Safa, Mostafa, Habib Doutoum Sadia, Mohamed Mahmoud Saleh, Dina, Samir, Mohamed Yahia Mohamed Ali, Mahmoud, A Nassar, Samar, Abdelhady, Aly, Abdelrazek, Israa, Abdelsalam, Aya, El-Sawy, Eman, Essam, Mohamed, Gadelkarim, Khaled, Ghaly, Mohamed, Hassabalnaby, Rana, Masarani, Nourhan Mohamed Shaaban, Ahmed, Sabry, Menatalla, Salem, Nourhan Akram Soliman, Diaaaldin, Zahran, Moustafa Ramadan Abou El Soud, Esraa Tarek Badr, Hala, Borham, Nehal, Elmeslemany, Mohammad, Elsayed, Fawzia, Elsherif, Sara, Eslam, Gehad, Gaber, Sondos, Ibrahim, Yara, Kamh, Abdelrahman, Mahmoud, Shimaa Gamal Mohamed, Eman, Morshedy, Cinderella, Omar, Fatima Salem Soliman, Shaza, Abdelkawy, Naglaa, Abdelmohsen, Mahmoud, Abdelshakour, Ahmed, Dahy, Norhan, Gamal, Mohammed, Gamal, Ahmad, Hasan, Helal, Hetta, Nehad, Mousa, Mohamed, Omar, Somia, Rabie, Mahmoud, Saad, Bakeer, Saleh, Marwa Sayed Mohamed, Muhammad, Shawqi, Heba Abdelhady Mousa, Mostafa, Alnoury, Mohamed, Elbealawy, Ahmed, Elshafey, Muhammad Essam Ibrahim El Desouki Muhammad Ahmed, Mennatullah, Ghonaim, Fawzy, Hgag, Mohamed, Ibrahim, Mahmoud, Morsy, Mohamed Reda Loaloa, Ahmed, Refaat, Hadeer, Samir, Fatma, Shahien, Mohamed, Sobhy, Fathy, Sroor, Esraa, Abdellatif, Marina, Adel, Amr Abdelghani Afifi, Eman, Afifi, Marco, Antaky, Amr, Dawoud, Naira El Zoghby, Amira, El-Remaily, Ali Abdelazez Elzanfaly, Ahmed, Gadallah, Fatma Alzahraa Gamal, Omar, Hashem, Shrouk Medhat Youssef, Aliaa Muhammad Attyah, Malak, Munir, Omar, Shazly, Esraa, Taha, Karim, Wilson, Sawsan, Adel, Asmaa, Ali, Esraa, Eid, Esraa, Elhelow, Marwa, Elmahdy, Bassant, Elshatby, Amany Hossam El-Din Zakaria, Ahmad, Hossny, Eman, Ibrahim, Ahmed, M Yonis, Maram, Metwalli, Basant, Yousry, Esraa, Zid, Mina, A Yacoub, Ahmed, Abdelhakim, Nervana, Abouelsoad, Mo'Min, Alkhatib, Ahmed, Ashraf, Alaa, Ashraf, Yasmin, Elazab, Mahmoud, Elfanty, Osama, Elkabir, Mai, Elsayed, Ahmed, Elshimy, Hager, Elsobky, John, Eskander, Ahmed, Gad, Ward, Hamsho, Noura Khaled Abdelwahed, Menna, Magdy, Dalia, Moharam, Abeer, Osama, Shereen, Ramadan, Radwa, Roum, Taqwa, Sayed, Tarneem, Shehada, Ahmed Mohy Zidan, Khalid, Abbas, Amr, Ali, Mohamed, Attia, Mohamed, Balata, Ayman El Nakeeb, Mohamed Ibrahim Elsayed Elewaily, Ahmed, Elfallal, Hossam, Elfeki, Ahmed, Elkhadragy, Sameh, Emile, Helmy, Ezzat, Hasnaa, Hosni, Islam, Mansour, Waleed, Omar, Gehad, Othman, Kareem, Sadek, Mostafa, Shalaby, Noura, Shehab-Eldeen, Rawda Anas Khalifa, Helmy, Badr, Mostafa, Eldeep, Ahmed, Eldeep, Amany Eldoseuky Mohammed, Salwa, Khallaf, Eman Magdy Hegazy, Rokia, Mahmoud, Pola, Mikhail, Mahmoud, Morsi, Sara, Mowafy, Dina, Raafat, Amina, Safy, Marwa, Sera, Ahmed Shible Sera, Mostafa Salim Mohamed AbdAllah, Muhammad, Abdelkader, Abdulrahman Osama Abdou, Ahmedgaber, Ahmed, Shireen, Gaafar, Fatma Ibrahim Negm, Mina, Lapic, Ahmed, Maher, Hagar, Mahmoud, Ahmed, Mostafa, Mohamed, Samir, Fatma, Samy, Nourhan, Semeda, Hind, I Shalaby, Alaa, El-Taweel, Ahmed Galal Elnagar, Ahmed Gamal Hemidan, Mohamed, Hussein, Ahmed, A Kandil, Moawad, Mf, Ayat Allah Nasser Hamamah, Mostafa, Soliman, Mohamed, Abdelkhalek, Noura Abdelmaksoud Tawakel, Ahmed Mohamed Abdelwahed, Alrawy, Abdou, Khalid, Atallah, Mohammed Yasser Elsherbeny, Eman, Emara, Mohamed, Hamdy, Omar, Hamdy, Amira, Haron, Salma, Ismail, Islam Hany Metwally, Nihal Mohamed Hamed Elgaml, Ahmed, Nassar, Basel, Refky, Mirna, Sadek, Mahmoud, Saleh, Asmaa, Yunes, Mai, Zakaria, Mohammed, Zuhdy, Notila, Fayed, Mohammed Mustafa Hassan Mohammed, Sander, Kütner, Priit, Melnik, Indrek, Seire, Toomas, Ümarik, Eppu, Ainoa, Verner, Eerola, Hanna, Koppatz, Laura, Koskenvuo, Ville, Sallinen, Sini, Takala, Jevgeni, Katunin, Arto, Turunen, Niki, Christou, Muriel, Mathonnet, Vincent, Lavoue, Krystel Nyangoh Timoh, Lucie, Soulabaille, Romain, Lesourd, Aude, Merdrignac, Laurent, Sulpice, Benoît, André, Elodie, Chantalat, Charlotte, Vaysse, Bertrand, Dousset, Sebastien, Gaujoux, Gregory, Martin, Octavian, Clonda, Domantas, Juodis, Klaus, Kienle, Andras, Mravik, Samuel, Palmer, Gabor, Szabadhegyi, Anita Eseenam Agbeko, Solomon, Gyabaah, Frank Enoch Gyamfi, Nuhu, Naabo, Atta Owusu Senior, Joseph, Yorke, Frank, Owusu, Francis, Abantanga, Theophilus Teddy Kojo Anyomih, Abdul-Jalilu Mohammed Muntaka, Emmanuel Owusu Abem, Mohammed, Sheriff, Paul, M Wondoh, Dimitrios, Balalis, Dimitrios, Korkolis, Georgios, Gkiokas, Eirini, Pantiora, Theodosios, Theodosopoulos, Argyrios, Ioannidis, Konstantinos, Konstantinidis, Sofia, Konstantinidou, Nikolaos, Machairas, Anna, Paspala, Anastasia, Prodromidou, Christos, Chouliaras, Konstantinos, Papadopoulos, Ioannis, Baloyiannis, Ioannis, Mamaloudis, George, Tzovaras, Ioanna, Akrida, Maria-Ioanna, Argentou, Stylianos, Germanos, Evangelos, Iliopoulos, Ioannis, Maroulis, George, Skroubis, George, Theofanis, Christos, Chatzakis, Orestis, Ioannidis, Lydia, Loutzidou, Panagiotis, Karathanasis, Nikolaos, Michalopoulos, Charalampos, Theodoropoulos, Dimitrios, Theodorou, Tania, Triantafyllou, Zoe, Garoufalia, Natasha, Hasemaki, Michalis, Kontos, Gregory, Kouraklis, Stylianos, 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Telma, Fonseca, Jorge, Pereira, Juan, Rachadell, Ana, Torre, Filipe Madeira Martins, Ana Cristina Carvalho, Joana Rodrigues Ferreira, Bruno Ribeiro da Silva, Helena, Devesa, Ana, Vieira, Inês, Mónica, Margarida, Amaro, Diogo, Sousa, Marta, Reia, João, Louro, Ana, Martins, Joaquina, Dominguez, Inês, Santos, Nuno Miguel Freitas Oliveira, José Carlos Pereira, Pedro, Silva-Vaz, Ligia, Freire, Ricardo, Escrevente, Valentina Madalina Negoita, Dmitry, Shakhmatov, Yves, Nezerwa, Radosav, Radulovic, Gareth, Obery, Francois, Viljoen, Tome, Mendes, Antonio, Suarez, Enrique, Moncada, Maria, Fernandez-Hevia, Carolina Curtis Martínez, Julia Maria Gil Garcia, Mariana González Zunzarren, Tarig, Idris, Karolina, Eklöv, Oskar, Grahn, Leila, Amin, Malin, Blomqvist, Costanza, Ajani, Rebecca, Kraus, Nico, Seeger, Melissa, Willemin, Fadi, Rayya, Mohammad, Ayash, Raneem, Msouti, Israa, Kannas, Eias, Abazid, Asil, Esper, Skander, Slim, Akil Serdar Kavcar, Erman, Aytac, Ahmet Cem Dural, Ayse, Ilker, Ismail Cem Eray, Eray, Kurnaz, Saygin, Altiner, Mustafa Deniz Tepe, Can, Şahin, Evrim, Savli, Aryon, Innocent, Lilian, Babirye, Andrii, Diachenko, Vladislav, Hordoskiy, Heather, Curry, Charlene Yat Che Chau, Harry, Robertson, Arin, Mahmoud, Hannah, Lennon, Lynette, Loi, Emily, Kirkham, Cameron, Mccann, Daniel, Watts, Binay, Gurung, Michael, Wilson, Thomas, Tribedi, Eleonora, Garofalo, Baryab, Zahra, Scott, Macdonald, Ian, Daniels, Nathan, Ng, Shivun, Khosla, James, Olivier, Sum Yu Pansy Yue, Gayathri, Suresh, Jack, Wellington, Emmanuel, Lorejo, Mafdi, Mossaad, Madison, Crutcher, Marjan, Alimi, Ioana, Baiu, Hossam, Abdou, Alison, Conway, Connor, Peck, Mauro Andres Perdomo Perez, Stanley, Zulu, Mildred, Nakazwe, Sule, Burger, Justine, Davies, Rachel, Donaldson, Chikwendu, Ede, O James Garden, Chiapo, Lesetedi, Charles, Mabedi, Laura, Magill, Felix Makinde Alakaloko, Alex, Makupe, Mark, Monahan, Soloman, Mulira, Elmi, Muller, Jospeh, Musowoyo, Jean Léon Olory-Togbe, Tracey, Roberts, Martin, Smith, 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Harmony Impellizzeri, Marco Inama, Gianluigi Moretto, Sylvie Mochet, Elisa Ponte, Antonella Usai, Stefano Mancini, Andrea Sagnotta, Luigi Solinas, Elisa Bolzonaro, Nicolò Tamini, Gianluca Curletti, Raffaele Galleano, Michele Malerba, Sofia Campanella, Gianfranco Cocorullo, Francesco Colli, Paolino De Marco, Nicolò Falco, Tommaso Fontana, Leonel Jospin Kamdem Mambou, Antonella La Brocca, Leo Licari, Brenda Randisi, Giovanna Rizzo, Giulia Rotolo, Giuseppe Salamone, Roberta Tutino, Paolina Venturelli, Stefano Malabarba, Alessandro Sgrò, Ivan Vella, Bruno Cirillo, Daniele Crocetti, Giorgio De Toma, Pierfrancesco Lapolla, Andrea Mingoli, Paolo Sapienza, Angela Belvedere, Stefania Bianchini, Margherita Binetti, Arianna Birindelli, Valeria Tonini, Mauro Podda, Fabio Pulighe, Michele De Rosa, Lorenzo Bono, Felice Borghi, Paolo Geretto, Maria Carmela Giuffrida, Corrado Lauro, Alessandra Marano, Luca Pellegrino, Paola Salusso, Diego Sasia, Michela Campanelli, Alberto Realis Luc, Mario Trompetto, Roberto Cardia, Nicola Cillara, Antonio Nicola Giordano, Antonio Costanzo, Mario Alessandro Giovilli, Luca Turati, Silvestro Canonico, Gianluca Pellino, Guido Sciaudone, Francesco Selvaggi, Lucio Selvaggi, Nader Albsoul, Ahmad AlBsoul, Ala'a Aldeen Alkhatib, Osama Alsallaq, Justin Z Amarin, Rami Ayoub, Isam Bsisu, M S El Muhtaseb, Mohammad Jabaiti, Jamal Melhem, Ibrahim Nour, Yasmeen Z Qwaider, Mohammad Hasan Salameh, Ahmad Suleihat, Haya H Suradi, Mohammad Alammarin, Almoutuz Aljaafreh, Mohammad Bani Hani, Zeina Bani Hani, Farah Bani Hani, Toqa Fahmawee, Shadi Hamouri, Cyrine Katanani, Ra'fat Tawalbeh, Tamara Tawalbeh, Hassan Zawahrah, Mohamad K Abou Chaar, Lana Abusalem, Mahmoud Al-Masri, Hani Al-Najjar, Lutfi Barghuthi, Zahra Ahmed, Adnan Maulana, Omar Ngotho, Charbel Kamau, Aruyaru Stanley Mwenda, Fridah Bosire, Elizabeth Mwachiro, Robert Parker, Ian Simel, Kimutai Sylvester, Abdulmunem Ahmed Mustafa Althini, Sofian Elbarouni, Aya Elseed Elbeshina, Ahmed Gwea, Ans Malek, Wedad Albashir Masoud Farag, Abdulwahab Abdalei, Abu Baker Abdel Malik, Areej Abo-Khammash, Ma'aly Abuhlaiga, Nour Adnan, Marwa Albaggar, Asma Alfitory, Asma Aljanfi, Fakhruddin Almuzghi, Zohoor Altumei, Fatima Alzabti, Hana Ashoushan, Mohamed Assalhi, Joma Azzubia, Sondos Bnhameida, Malik Delhen, Houssein Elshafei, Hana Elteir, Fatima Esbaga, Abdel Aziz Gobbi, Fatma Hamouda, Hamdan Hilan, Rania Ismail, Fieruz Jebran, Muataz Kasbour, Galia Maderi, Saja Mohammad, Burooj Mohammed, Habib Murtadi, Hamassat Mustafa, Mohamed Rajab, Sarah Trenba, Mariam Wafaa, Eman Al Sagheir, Alabas Almigheerbi, Ahmed Alzahaf, Sumayyah Ghayth Bahroun, Najah Ben Dallah, Mahmoud Elshaibani, Haitem Eswaye, Maha Karar, Samah Omar, Eman Younes, Maha Younes, Dafer Zreeg, Saleh Abujamra, Firas Ashour, Mala Elgammudi, Wesal Omar F Aljadidi, Enas Saddouh, Randa Sharif, Aya Alabuzidi, AbdulMawlay Alwerfally, Sarra Aribi, Fatma Bibas, Taha Elfaituri, Yasmine Elhajjaji, Ala Khaled, Wegdan Khalil, Tesneem Layas, Enas Soula, Ahmed Tarek, Muad Fathi Khalleefah Abu Hallalah, Saleh Abujamra, Hazem Abdelkarem Ahmed, Tagwa Alsharef, Abdulsalam Ali Ben Saoud, Tasnim El Gharmoul, Ahmed Elhadi, Safa Elrais, Abdulhalim Shebani, Heba Zarti, Asaid Zeiton, Marijus Ambrazevicius, Nerijus Kaselis, Migle Stakyte, Oleg Aliosin, Agne Cizauskaite, Sarunas Dailidenas, Vitalijus Eismontas, Migle Kybransiene, Vitalija Nutautiene, Narimantas Samalavicius, Dainius Simcikas, Algirdas Slepavicius, Albinas Tamosiunas, Nerijus Ubartas, Paulius Zeromskas, Saulius Bradulskis, Edvinas Dainius, Juozas Juočas, Egle Kubiliute, Juozas Kutkevičius, Aurimas Opolskis, Audrius Parseliunas, Andrejus Subocius, Donatas Venskutonis, Egle Virbickaite, Diana Zuikyte, Algirdas Bogusevicius, Kristina Buzaite, Daiva Čepuliené, Ieva Cesleviciene, Vaidotas Cesna, Jolanta Gribauskaite, Povilas Ignatavicius, Mantas Jokubauskas, Monika Liugailaitè, Ernest Margelis, Ruta Mazelyte, Lina Pankratjevaitè, Matas Pažusis, Agne Rackeviciute, Justina Saladyte, Monika Škimelytè, Vygintas Šlenfuktas, Monika Sudeikyte, Algimantas Tamelis, Tomas Vanagas, Žygimantas Žumbakys, Aivaras Atkociunas, Audrius Dulskas, Justas Kuliavas, Justas Birutis, Sigitas Paškevičius, Mindaugas Šatkauskas, Donatas Danys, Matas Jakubauskas, Lina Jakubauskiene, Marius Kryzauskas, Vytautas Lipnickas, Gabija Makūnaitè, Fanjandrainy Rasoaherinomenjanahary, Herizo Rasolofonarivo, Luc Hervé Samison, Bitiel Banda, Precious Malemia, Vanessa Msosa, Ahmad Imran Ahmad Izzuddin, Andre Das, Ying Yee Gan, Tan Shong Sheng, Jia Yng Siaw, Mohd Fadliyazid Ab Rahim, Dyg Zahratul Hamrak Abang Jamari, Nurfariza Che Husin, Muhd Yusairi Kamarulzaman, Yi Ping Lim, Nil Amri Mohamed Kamil, Mohd Razeen Mohd Hassan, Saidah Mohd Sahid, Johari Mustafa, Elaine Hui Been Ng, Wan Khamizar Wan Khazim, Ng Chang Ern, P G Lingeshan, Syariz Ezuan Sulaiman, Sue Ean Ang, Muhammad Navid Bin Mohamad Sithik, Yih Jeng Cheong, Mahadevan Deva Tata, Law Jia Xian, Aravinthan Kadravello, I-Ern Koh, Li-Yen Ng, Yuki Julius Ng We Yong, Kandasami Palayan, Chi Xuan Sam, Phuah Siow Jin, Jeremy Tan Ern Hwei, Yita Tang, Alvin Zubin Ter, Michael Pak-Kai Wong, Andee Dzulkarnaen Zakaria, Zaidi Zakaria, Fitjerald Henry, Thyivya Kalaiselvan, Muhammad Fairuz Shah Abd Karim, Mohamed Rezal Abdul Aziz, Nora Abdul Aziz, Tak Loon Khong, Peng Choong Lau, Hiong Chin Lim, April Camilla Roslani, Jonathan Chen Ken Seak, Sui-Weng Wong, Lai Fen Wong, Leow Yeen Chin, Mercy Chinemerem Anyanwu, Elaine Borg, Zachary Busuttil, Thomas Calleja, Kurt Lee Chircop, Ruth Cutajar, Andrew Michael Dimech, Sarah Ellul, Joseph Galea, Kiara Gascon Perai, Ruth Gatt, Lisa Kelman, Elizabeth Micallef, Favour Nwolu, Kim Sammut, Joanna Thompson, Sean Warwicker, Matthew Zammit, Fernando Cordera, Efraín Cruz González, Jorge Sánchez-García, Francisco José Barbosa Camacho, Francisco Javier Barrera López, Carlos Jose Zuloaga Fernandez Del Valle, Eric Acosta, Iván Romarico González Espinoza, Perla Moreno, Ana Olivia Cortes-Flores, Clotilde Fuentes Orozco, Alejandro Gonzalez Ojeda, Samantha Corro Díaz González, Laura Martinez, Antonio Ramos-De la Medina, Bonifacio Mosqueda Amador, Armando Novoa, Dennet Arturo Olazo Espejo, Alejandro Jimenez, Federico Lopez Rosales, Elva Gabriela Vanoye, Luis Alberto Garcia Gonzalez, Roberto Carlos Miranda-Ackerman, Manuel Solano-Genesta, Alethia Alvarez-Cano, Hector Hugo Romero-Garza, Heriberto Medina-Franco, Lorelí Mejía-Fernández, Noel Salgado-Nesme, Omar Vergara-Fernandez, Guadalupe Montserrat Gutiérrez-Mota, Francisco Xavier Hernandez Vera, Anabella Llantada Lopez, Gilberto Morgan Villela, Felipe de Jesus Ramirez Padilla, Walezka Tapia Marin, Mónica Martínez Maldonado, Ramses Sánchez Suárez, José Manuel Troche, Chaymae Benyaiche, Oumaima Outani, Souadka Amine, Amine Benkabbou, Anass Mohammed Majbar, Raouf Mohsine, Ali Rafik, Thida Oung, Moe Moe Tin, David W Borowski, Philipp Plarre, David W Borowski, Philipp Plarre, Anna Alberga, Nina Sluiter, Jurriaan Tuynman, Robin Blok, Didem Cömert, Roel Hompes, Marianne Kalff, Merel Elisabeth Stellingwerf, Pieter Tanis, Mark van Berge Henegouwen, Elise Maria van Praag, Daan Wisselink, Michael Gerhards, Josephine Lopes Cardozo, Emma Westerduin, Joske de Jonge, Aaw van Geloven, Kaz van Schilt, Frank den Boer, Simone Stoots, Stijn Vlek, Jamie Adams, Ibrahim S Al-Busaidi, Gabrielle Budd, Seung Il Choi, Michael Jen Jie Chu, Anurag Ganugapati, Lucy McKinstry, Rebecca Pascoe, Simon Richards, Kenrick Rosser, Annie Stevenson, Rebecca White, Shebani Farik, Jin Kwun, Ahmed Murad, Sarah Cowan, Timothy Hall, Michael Hayton, Laminou Malam Sani, Souleymane Oumarou Garba, Harissou Adamou, Ibrahim Amadou Magagi, Oumarou Habou, Halima Aliyu, Muhammad Daniyan, Tunde T Sholadoye, Lawal Abdullahi, Lofty-John Anyanwu, Aminu Mohammad Mohammad, Abubakar Bala Muhammad, Abdurrahman Abba Sheshe, Ibrahim Suleiman, Alaba Adesina, Ajibola Awolowo, Clement Onuoha, Omotayo Salami, Ogechukwu Taiwo, Agboola Taiwo, Stephen Kache, Jerry Godfrey Makama, Danjuma Sale, Olajide Abiola, Akinlabi Ajao, Anthony Ajiboye, Amarachukwu Etonyeaku, Julius Olaogun, Ademola Adebanjo, Opeoluwa Adesanya, Michael Olatunji Afolayan, Olanrewaju Balogun, Ayomide Makanjuola, Samuel Nwokocha, Rufus Wale Ojewola, Thomas Olagboyega Olajide, Adewale Aderounmu, Abdul-Rashid Adesunkanmi, Adewale Adisa, Augustine Agbakwuru, Adeleke Akeem Aderogba, Olusegun Isaac Alatise, Olukayode Arowolo, Oladejo Lawal, Tajudeen Mohammed, Chinedu Ndegbu, Olalekan Olasehinde, Funmilola Wuraola, Akinbolaji Akinkuolie, Amarachukwu Etonyeaku, Arinzechukwu Mosanya, Omobolaji Ayandipo, Peter Elemile, Taiwo Akeem Lawal, Samuel Ali Sani, Stephen Garba, Rebecca Hauwa Sani, Samson Olori, Henry Onyebuashi, Ifeanyi Umoke, Adedire Adenuga, Ademola Adeyeye, Olufemi Habeeb, Bashir Lawal, Abdulrasheed Nasir, Eirik Kjus Aahlin, Didrik Kjønås, Elisabeth Myrseth, Jibran Abbasy, Abdul Alvi, Omair Saleem, Asma Afzal, Anam Nazir, Muhammad Farooq, Ayesha Liaqat, Syed Asghar Naqi, Ali Raza, Muzna Sarfraz, Muhammad Sarwar, Muntaha Banglani, Ambreen Munir, Rahmat Sehrish, Bushra Ayub, Raza Sayyed, Amna Altaf, Saima Ayub, Ahmad Uzair Qureshi, Komal Saeed, Bilal Syed, Sana Amir Akbar, Abdul Wahid Anwer, Ruqayya Naheed Khan, Amina Iqbal Khan, Shahid Khattak, Sameen Mohtasham, Muhammad Asad Parvaiz, Aamir Ali Syed, Abdul Basit Ansari, Noman Shahzad, Tanwir Khaliq, Isbah Rashid, Shahzad Hussain Waqar, Hasan Abu Al-Saleem, Amjad Abu Alqumboz, Mohammad Alqadi, Adham Amro, Rawan Assa, Eman Awesat, Rawan Ayyad, Mohammed Hammad, Ayat Haymony, Bassel Hijazi, Bara Hmeidat, Rowaa Lahaseh, Aseel Qawasmi, Alaa Rajabi, Mohammed Shehada, Sundus Shkokani, Yasmine Yaghi, Nadine Yaghi, Mohammad AlZohour, Mohammad Farid, Yousef Mahmoud Habes, Wesam Juba, Yanal Nubani, Abdelrahman Rabee, Mohammad Sa'deh, Saeed Abed, Iyad Al Basos, Mohammad Alswerki, Dina Ashour, Israa Awad, Samar Diab, Alaa El Jamassi, Sahar El-Kahlout, Somaya Elhout, Ahmed N K Hajjaj, Doaa Hasanain, Baraa Nabil Hajjaj, Mohammed Obaid, Eman Saikaly, Ahmed Salhi, Hiba Al-Tammam, Murad Almasri, Muath Baniowda, Doha Beshtawi, Ali Horoub, Rami Misk, Bayan Mohammad, Rami Qasrawi, Tasnim Sholi, Samar Abu-Nimeh, Abrar Abu-Srour, Sadi A Abukhalaf, Samer Adawi, Barah Alsalameh, Kholoud Ayesh, Muawiyah Elqadi, Ahmad Hammouri, Fatima Karim Mustafa, Natalie Marzouqa, Shatha Melhem, Dima Miqdad, Balqees Mohamad, Mhammed Rawhi, Ayman B Abu Ahammala, Ahmed Abu Ataya, Israa Abu Jayyab, Samar Al-Shwaikh, Othman Alagha, Mohammed Alasttal, Haneen Awadallah, Mahmood Elblbessy, Jehad Fares, Akram Jarbou, Ibtisam Mahfouz, Moath A Albahnasawi, Asmaa' Abo Mahadi, Hasan Abuelhatal, Ayham Abuelqomboz, Abdelrahman Almoqayyad, Abdallah Alwali, Reem Balaawi, Mahmoud Hamouda, Mohammed Humeid, Abdullah Jedyan, Tasneem Mahmoud Abu Hamam, Ghadeer Matar, Ali Salem, Tahani Samra, Nureddin Shaheen, Karam Shihada, Ayoob A Nemer, Mahmoud Abu Al Amrain, Abdulwhhab Abu Alamrain, Najlaa Abu Jamie, Mohammed R Abu-Rous, Nada Alfarra, Mohammed AlTaweel, Noor Alwhaidi, Ramadan Hamed, Bader Saqqa, Ahmad Shaheen, Dana Aljaber, Loay Aljaberi, Malak Alwaheidi, Assef Jawaada, Hani Khaldi, Rami Qahoush, Jalil Qari, Rana Saadeh, Ahlam Salim, Aseel Yacoub, Abbas Abbas, Rana Abu Shua'ib, Baraa Abu Zainah, Mahmoud AbuSirrees, Basheer Babaa, Ola Barhoush, Asef Belal Qadomi, Laith Daraghmeh, Reema Haji, Alaa Khatatbeh, Lana Khatib, Salsabeel Qarariah, Yara Quzmar, Khalil Safadi, Roqaya Salameh, Mohammad Hassan, Shifaa Herzallah, Loai Massad, Ahmed Nazzal, Ranin Nazzal, Dennis Escobar, Gustavo Miguel Machain V, Agustin Rodriguez Gonzalez, Jorge Emerson Chachaima Mar, Nathaly Olga Chinchihualpa Paredes, Vicente Cuba, Walter Lopez, Maria Milagros Niquen Jimenez, Nestor Alberto Sanchez Bartra, Olenka Sapallanay Ojeda, Diego Sequeiros, Andrea Toscano Pacheco, María Vergara, Sol Abarca, Rodrigo Alcorta, Giuliano Borda-Luque, Ivan Edward Eusebio Zegarra, Claudia Luján López, Mirella Marrufo, Cinthya Mogrovejo, Andrea Nomura, Yamile Rodríguez Angeles, Maitza Rosario Vidal Meza, Gabriela Zavala, José Neiser Castillo Arrascue, Jomara Caroline Hidrogo Cabrera, José Julio Mariano Larrea Vera, Miguel Osorio, Edgar Alcides Ylatoma Díaz, Mark Anthony Fontanilla, Joseph Roy Fuentes, Anna Leah Salazar, Genieve Dominguez, Marc Paul Lopez, Shiela Macalindong, Mark Augustine Onglao, Arjel Ramirez, Marie Dione Sacdalan, Mayou Martin Tampo, Gemma Leonora Uy, Jeremiah Mangahas, Kenneth Yabut, Joannes Paul Cañete, Bernalynn Eris Cansana, Ernes John Castro, Maria Kaiserin Lipana, Manuel Francisco Roxas, Vlu Jean Zara, Maciej Chroł, Paula Franczak, Michał Orłowski, Piotr Budzyński, Andrzej Budzyński, Pawel Bury, Agata Czerwińska, Jadwiga Dworak, Jacek Dziedzic, Michał Kisielewski, Jan Kulawik, Anna Lasek, Piotr Major, Piotr Małczak, Marcin Migaczewski, Michał Pędziwiatr, Magdalena Pisarska, Dorota Radkowiak, Mateusz Rubinkiewicz, Anna Rzepa, Tomasz Skoczylas, Maciej Stanek, Katarzyna Truszkiewicz, Mateusz Wierdak, Marek Winiarski, Piotr Zarzycki, Anna Zub-Pokrowiecka, Piotr Kowalewski, Rafał Roszkowski, Maciej Walędziak, Miguel Tomé, Sara Patrocinio, Ines Guerreiro, Filipe Almeida, Xavier de Sousa, Nuno Monteiro, Maria Teresa Costa Santos, Daniela de Oliveira, Marta Lopes Serra, Daniela Morgado, Christian Neves, Ana Carolina Oliveira, Alice Pimentel, Sofia Silva, Márcia Carvalho, Lúcia Carvalho, Joana Magalhães, Leonor Matos, Tânia Monteiro, Carlota Ramos, Vanessa Santos, José Barbosa, Jose Costa-Maia, Vítor Devezas, Ana Fareleira, Cristina Fernandes, Diana Gonçalves, Henrique Mora, Marina Morais, Fabiana Silva de Sousa, Sara Catarino Santos, Ana Logrado, André Tojal, Edgar Amorim, Miguel F Cunha, Ana Fazenda, João Pedro Melo Neves, Inês Isabel Sampaio da Nóvoa Gomes Miguel, Diogo Veiga, José Azevedo, Hugo Cardoso Louro, Mariana Leite, José Azevedo, Maria Bairos Menezes, Bárbara Gama, Diana Brito, Marta Cristina Cruz Martins, André Graça E Magalhães, Ana Catarina Longras, Rita Lourenço, Diana Matos, Luis Castro, Filipa Policarpo, Joana Romano, Mariana Leite, Cristina Monteiro, Diogo Pinto, Marina Duarte, Sónia Fortuna Martins, Mariline Oliveira, Diogo Galvão, Lisandra Martins, Anaisa Silva, Viorel Taranu, Bárbara Vieira, Jessica Neves, Simone Oliveira, Hugo Ribeiro, Margarida Cinza, Rosa Felix, Arnaldo Machado, Joana Oliveira, Joana Patrício, Rita Pedroso de Lima, Mário Pereira, Miguel Rocha Melo, Cristina Velez, Alberto Abreu da Silva, Mariana Claro, Daniel Costa Santos, Andreia Ferreira, Hugo Capote, Daniela Rosado, Filipa Taré, Oriana Nogueira, Miguel Ângelo, José Miguel Baiao, Andreia Guimarães, João Marques, Miguel Nico Albano, Marta Silva, Ana Valente da Costa, Teresa Vieira Caroço, Sara Almeida Braga, Ines Capunge, Marta Fragoso, João Guimarães, Bruno Pinto, João Ribeiro, Miguel Angel, Guilherme Fialho, Monica Guerrero, Filipa Campos Costa, Diogo Cardoso, Vasco Cardoso, Magda Alves, Inês Estalagem, Tiago Louro, Cláudia Marques, Rita Martelo, Miguel Morgado, Rita Canotilho, Ana Margarida Correia, Pedro Martins, Mariana Peyroteo, João Gomes, Rita Monteiro, Manuela Romano, Daniela Macedo Alves, Rita Peixoto, Catarina Quintela, Maria João Jervis, Débora Melo, André Pacheco, Valter Paixão, Vera Pedro, Joana Pimenta, João Pimenta de Castro, Ana Rocha, Mircea Beuran, Matei Razvan Bratu, Cezar Ciubotaru, Bogdan Diaconescu, Sorin Hostiuc, Ionut Negoi, Bogdan Stoica, Evgeny Anokhin, Georgy Kuznetsov, Giorgi Oganezov, Fedor Paramzin, Ekaterina Romanova, Valeryan Rutkovskii, Vasilii Rutkovskii, Mikhail Shushval, Mikhail Zabiyaka, Khasan Dzhumabaev, Valerii Ivanov, Zaman Mamedli, Sergey Achkasov, Artem Balkarov, Elnur Nabiev, Marat Nagudov, Evgeny Rybakov, Karina Saifutdinova, Oleg Sushkov, Armen Vardanyan, Ainhoa Costas-Chavarri, Lule Joseph, Isaac Ndayishimiye, J C Allen Ingabire, Ntirenganya Faustin, Alphonse Zeta Mutabazi, Jean Paul Mvukiyehe, Vizir J P Nsengimana, Carine Uwakunda, Mohammad Monir Abbas, Nouf Akeel, Murad Aljiffry, Kholoud Awaji, Ali Farsi, Ghader Jamjoum, Ahmad Khoja, Ashraf Maghrabi, Nadim Malibary, Mohammed Nassif, Abdulaziz Saleem, Abdullah Sultan, Wail Tashkandi, Hanaa Tashkandi, Nora Trabulsi, Mouhamadou Bachir Ba, Adja Coumba Diallo, Abdourahmane Ndong, Vladica Cuk, Uroš Janković, Jovan Juloski, Sharon Zhiling Koh, Frederick Koh, Kuok Chung Lee, Kai Yin Lee, Sean Lee, Wei Qi Leong, Bettina Lieske, Su Ann Lui, Prajwala Prakash, Jan Grosek, Gregor Norcic, Ales Tomazic, Nicolas Fitchat, Robert Jaich, Devorah Wineberg, Modise Zacharia Koto, Daniella Baiocchi, Damian Clarke, Christina Johanna Steenkamp, Stephanie Van Straten, Sharon Bannister, Adam Boutall, Galya Chinnery, Anna Coccia, Angela Dell, Parveen Karjiker, Christo Kloppers, Nicholas Loxton, Tumi Mabogoane, Francois Malherbe, Eugenio Panieri, Shreya Rayamajhi, Richard Spence, Tirsa van Wyngaard, Claire Warden, T E Madiba, Yoshan Moodley, Nivashen Pillay, Savannah Brooks, Charlise Kruger, Lisa Hannah Van Der Merwe, Ferhana Gool, Maahir Kariem, Heather Bougard, Kathryn Chu, Nazmie Kariem, Fazlin Noor, Reantha Pillay, Leandi Steynfaardt, Lucía González González, José Miguel Marín Santos, Paula Martín-Borregón, Javier Martínez Caballero, Cristina Nevado García, Pastora Rodriguez Fraga, Gonzalo De Castro Parga, Maria Pilar Fernández Veiga, Lucía Garrido López, Hugo Infante Pino, Irene Lages Cal, Marta López Otero, Manuel Nogueira Sixto, Marta Paniagua García Señorans, Laura Rodríguez Fernández, Alejandro Ruano Poblador, Erika Rufo Crespo, Raquel Sanchez-Santos, Vincenzo Vigorita, Ester Alonso Batanero, Dorisme Asnel, Isabel Cifrian Canales, Elisa Contreras Saiz, Irene De Santiago Alvarez, Tamara Díaz Vico, Sebastian Fernandez Arias, Daniel Fernández Martínez, Carmen García Bernardo, Luis Joaquín García Flórez, Carmen Garcia Gutierrez, Manuel García Munar, Carlos Alberto Márquez Zorrilla Molina, Marta Merayo, José Luis Michi Campos, Maria Moreno Gijon, Jorge L Otero-Diez, Jose Luis Rodicio Miravalles, Lorena Solar-Garcia, Aida Suárez Sánchez, Nuria Truan, Cristina Alejandre 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E., Chinchihualpa Paredes, N. O., Cuba, V., Lopez, W., Niquen Jimenez, M. M., Sanchez Bartra, N. A., Sapallanay Ojeda, O., Sequeiros, D., Toscano Pacheco, A., Vergara, M., Abarca, S., Alcorta, R., Borda-Luque, G., Eusebio Zegarra, I. E., Lujan Lopez, C., Marrufo, M., Mogrovejo, C., Nomura, A., Rodriguez Angeles, Y., Vidal Meza, M. R., Zavala, G., Castillo Arrascue, J. N., Hidrogo Cabrera, J. C., Larrea vera, J. J. M., Osorio, M., Ylatoma Diaz, E. A., Fontanilla, M. A., Fuentes, J. R., Salazar, A. L., Dominguez, G., Lopez, M. P., Macalindong, S., Onglao, M. A., Ramirez, A., Sacdalan, M. D., Tampo, M. M., Uy, G. L., Mangahas, J., Yabut, K., Canete, J. P., Cansana, B. E., Castro, E. J., Lipana, M. K., Roxas, M. F., Zara, V. 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I., Veiga, D., Azevedo, J., Cardoso Louro, H., Leite, M., Bairos Menezes, M., Gama, B., Brito, D., Cruz Martins, M. C., Graca e Magalhaes, A., Longras, A. C., Lourenco, R., Matos, D., Castro, L., Policarpo, F., Romano, J., Monteiro, C., Pinto, D., Duarte, M., Fortuna Martins, S., Oliveira, M., Galvao, D., Martins, L., Silva, A., Taranu, V., Vieira, B., Neves, J., Oliveira, S., Ribeiro, H., Cinza, M., Felix, R., Machado, A., Oliveira, J., Patricio, J., Pedroso de Lima, R., Pereira, M., Rocha Melo, M., Velez, C., Abreu da Silva, A., Claro, M., Costa Santos, D., Ferreira, A., Capote, H., Rosado, D., Tare, F., Nogueira, O., Angelo, M., Baiao, J. M., Guimaraes, A., Marques, J., Nico Albano, M., Silva, M., Valente da Costa, A., Vieira Caroco, T., Almeida Braga, S., Capunge, I., Fragoso, M., Guimaraes, J., Pinto, B., Ribeiro, J., Angel, M., Fialho, G., Guerrero, M., Campos Costa, F., Cardoso, D., Cardoso, V., Alves, M., Estalagem, I., Louro, T., Marques, C., Martelo, R., Morgado, M., Canotilho, R., Correia, A. M., Martins, P., Peyroteo, M., Gomes, J., Monteiro, R., Romano, M., Alves, D. M., Peixoto, R., Quintela, C., Jervis, M. J., Melo, D., Pacheco, A., Paixao, V., Pedro, V., Pimenta, J., Pimenta de Castro, J., Rocha, A., Beuran, M., Ciubotaru, C., Diaconescu, B., Hostiuc, S., Negoi, I., Stoica, B., Anokhin, E., Kuznetsov, G., Oganezov, G., Paramzin, F., Romanova, E., Rutkovskii, V., Shushval, M., Zabiyaka, M., Dzhumabaev, K., Ivanov, V., Mamedli, Z., Achkasov, S., Balkarov, A., Nabiev, E., Nagudov, M., Rybakov, E., Saifutdinova, K., Sushkov, O., Joseph, L., Ndayishimiye, I., Faustin, N., Mutabazi, A. Z., Mvukiyehe, J. P., Nsengimana, V. J. P., Uwakunda, C., Abbas, M. M., Akeel, N., Aljiffry, M., Awaji, K., Farsi, A., Jamjoum, G., Khoja, A., Maghrabi, A., Malibary, N., Nassif, M., Saleem, A., Sultan, A., Tashkandi, W., Tashkandi, H., Trabulsi, N., Ba, M. B., Diallo, A. C., Ndong, A., Cuk, V., Jankovic, U., Koh, S. Z., Koh, F., Lee, K. C., Lee, K. Y., Lee, S., Leong, W. Q., Lui, S. A., Prakash, P., Grosek, J., Norcic, G., Tomazic, A., Fitchat, N., Jaich, R., Wineberg, D., Koto, M. Z., Baiocchi, D., Clarke, D., Steenkamp, C. J., Bannister, S., Boutall, A., Chinnery, G., Coccia, A., Dell, A., Karjiker, P., Kloppers, C., Loxton, N., Mabogoane, T., Malherbe, F., Panieri, E., Rayamajhi, S., van Wyngaard, T., Warden, C., Madiba, T. E., Pillay, N., Brooks, S., Kruger, C., Van Der Merwe, L. H., Gool, F., Kariem, M., Bougard, H., Kariem, N., Noor, F., Pillay, R., Steynfaardt, L., Gonzalez Gonzalez, L., Marin Santos, J. 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P., Montes-Manrique, M., Rodriguez-Lopez, M., Ruiz Soriano, M., Trujillo Diaz, J., Vazquez Fernandez, A., Argudo, N., Pera, M., Torrent Jansa, L., Garcia Dominguez, M., Goded, I., Roldon Golet, M., Talal El-Abur, I., Utrilla Fornals, A., Zambrana Campos, V., Aguilar Martinez, M. D. M., Bosch, M., Garcia-Catala, L., Sanchez-Guillen, L., Artigau, E., Gomez Romeu, N., Julia Bergkvist, D., Espina Perez, B., Morato, O., Olona, C., Dieguez, B., Forero-Torres, A., Losada, M., Gomez-Abril, S., Gonzalvez, P., Martinez, R., Navarro Martinez, S., Paya-Llorente, C., Perez Rubio, A., Santarrufina Martinez, S., Sebastian Tomas, J. C., Trullenque Juan, R., Gegundez Simon, A., Mate, P., Prieto-Nieto, M. I., Rubio-Perez, I., Urbieta, A., Vicario Bravo, M., Abello, D., Frasson, M., Garcia-Granero, A., Abad Gurumeta, A., Abad-Motos, A., Lucena-de Pablo, E., Nozal, B., Ripolles-Melchor, J., Salvachua, R., Ferrero, E., Garcia-Sancho Tellez, L., Picardo, A. L., Rojo Lopez, J. A., Zorrilla Matilla, L. 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W., Zimmermann, B., Bakoleas, P., Chanousi, I., Charalampidou, L., Grochola, L. F., Heid, F., Ntaoulas, S., Outos, M., Peros, G., Podolska-Skoczek, H., Reinisch, K. B., Zielasek, C., Demartines, N., Gilgien, J., Kefleyesus, A., St-Amour, P., Toussaint, A., Alhimyar, M., Alsaid, B., Alyafi, A., Alkhaledi, A., Kouz, B., Omarain, A., Al-Sabbagh, Y., Alkhatib, H., Sara, S., Alhaj, A., Danial, A., Kadoura, L., Maa Albared, S., Monawar, Y., Nahas, L., Abd, B., Saad, A., Wakkaf, H., Bouzaiene, H., Ghalleb, M., Akaydin, E., Akbaba, A. C., Atakul, O., Baltaci, E., Besli, S., Burgu, G., Cenal, U., de Muijnck, C., Demirkaya, H. C., Dogruoz, A., Gezer, Z. I., Gundogdu, Y., Kara, M., Korkmaz, H. K., Kurtoglu, G. K., Ozben, V., Ozmen, B. B., Pektas, A. M., Sel, E. K., Yenidunya, N., Bengur, F. B., Oral, B. M., Yozgatli, T. K., Abdullayev, S., Gunes, M. E., Sahbaz, N. A., Banaz, T., Kargici, K., Kuyumcu, O. F., Yanikoglu, E., Yesilsancak, M., Yilmaz, D., Aktas, M. K., Rencuzogullari, A., Isik, A., Leventoglu, S., Yalcinkaya, A., Yuksel, O., Kalayci, M. U., Kara, Y., Sarici, I. S., Akin, A., Alemdag, G. N., Arslan, E., Baki, B. E., Bodur, M. S., Calik, A., Candas Altinbas, B., Cihanyurdu, I., Erkul, O., Gul, B., Guner, A., Kose, B., Semiz, A., Sevim, Tayar, S., Tomas, K., Tufek, O. Y., Turkyilmaz, S., Ulusahin, M., Usta, A., Yildirim, R., Guler, S. A., Tatar, O. C., Varol, E., Kirimtay, B., Uysal, M., Yildiz, A., Kose, E., Ciftci, A. B., Colak, E., Eraslan, H., Kucuk, G. O., Yemez, K., Lule, H., Bienfait, M., Bua, E., Okalany, N., Basarab, M., Bielosludtsev, O., Kolhanova, K., Perepelytsia, K., Romanukha, K., Savenkov, D., Siryi, S., Tereshchenko, M., Viacheslav, N., Volovetskyi, A., Kebkalo, A., Tryliskyy, Y., Tyselskiy, V., Bruce, E., Chow, B. L., Iddles, E., Mcguckin, S., Newall, N., Ramsay, G., Sharma, P., Stewart, C., Wong, J., Badran, A., Bath, M., Belais, F., Butt, E., Joshi, K., Kapur, M., Shaw, M., Townson, A., Williams, C. Y. 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A., De Silva, K., Ekpete, O., Haque, S., Henderson, S., Ibrahim, B., Jayasinghe, T., Livie, J., Mailley, K., Nair, G., Tan, D., Baggaley, C., Dawidziuk, A., Szyszka, B., Barter, C., Gandhi, N., Hassell, K., Hitchin, S., Kelsall, J., Nagy, E., Nessa, A., Whisker, L., Yanni, F., Ali, M., Arora, D., Hediwattege, S., Kumarasinghe, N., Rathore, M., Tennakoon, A., Ali Ahmad, S. M., Bajomo, O., Nadira, F., Celentano, V., Griffiths, E., Karri, R. S., Mak, J. K. C., Pipe, M., Bhatti, M. I., Rabie, M., Boyle, C., Hamilton, D., Mihuna, A., Ng, J. C. K., Nicholson, G., Oliwa, A., Pearson, R., Rose, A., Yong, S. Q., Boereboom, C., Hanna, M., Walter, C., Greensmith, T. S., Mitchell, R., Monaghan, E., Crawford, J., Moug, S., Blackwell, J., Boyd-Carson, H., Herrod, P., Al-Allaf, O., Beattie, M., Bullock, C., Burman, S., Clark, G., Flamey, N., Flannery, O., Harding, A., Kodiatt, B., Lawday, S., Mahapatra, S., Mukundu Nagesh, N., Ng, M., Rye, D., Yoong, A., Clark, L., Deans, C., Edirisooriya, M., Carrington, E. V., Wong, T. L. E., Yusuf, B., Chamberlain, C., Duke, K., Kmiotek, E., Botes, A., Condie, N., Schrire, T., Shah, R., Thomas-Jones, I., Yates, C., Anthony, N., Matthews, E., Sahnan, K., Tankel, J., Tucker, S., Winter Beatty, J., Ziprin, P., Duggan, W., Kantartzi, A., Sridhar, S., Khaw, R. A., Srivastava, P., Underwood, C., Alves do Canto Brum, H., Chopra, S., Davis, L., Hughes, R., Tulley, J., Alberts, J., Athisayaraj, T., Olugbemi, M., Ahmad, K., Chan, C., Chapman, G., Fleming, H., Fox, B., Grewar, J., Hulse, K., Rutherford, D., Sinead, M., Speake, D., Vaughan-Shaw, P. G., Christodoulides, N., Kudhail, S., Welch, M., Husaini, S. M., Lambracos, S., Anyanwu, C., Suresh, R., Thomas, J. S., Gleeson, E., Platoff, R., Saif, A., Enumah, Z., Etchill, E., Gabre-Kidan, A., Bernstein, M., Carrano, F. M., Connors, J., Lynn, P., Melis, M., Newman, E., Foster, D. S., Perrone, K., Titan, A., Ahmad, S., Bafford, A. C. M. D., Dal Molin, M., Hanna, N., Zafar, S. N., Hemmila, M., Napolitano, L., Wong, J. J., Chandler, J., Wood, L., Wren, S., Ottesen, T., You, L., Yu, K., Arcienega Yanez, M. D. P., Ferreira Fernandes, M., Gonzalez, D., Cubas, S., Gonzalez, M. C., Zubiaurre, V., Demolin, R., Giroff, N., Sciuto, P., Campos, M., Rodriguez Cantera, G., Deepika, G., Simuchimba, E., Bulaya, A., Chibuye, C., Chirengendure, B., Kabale, M. -R., Kabongo, K., Munthali, J., Mweso, O., Pikiti, F., Otieno, J., Lai, L. T., Blackman, B., Subramaniam, S., Karim, R., Kok, N., Lee, Y. D., Ali, S., Sinha, A., Corrigan, R., Barnes, N., Wong, F., Dennis, G., Jedamzik, J., Phillips, E., Piette, W., Van hentenryck, M., Koco, H., Lawani, S., Kassa, M. W., Santos Bezerra, T., Gribnev, P., Dimitrov, D., Krastev, P., Oum, S., Bonghaseh, D. T., Al Farsi, M., Alsharqawi, N., Acevedo, V., Castillo Barbosa, A. C., Giron, F., Leon Rodriguez, J. P., Kucan, D., Rosko, D., Barsic, N., Zupan, D., Hegazi, A., Truncikova, V., Fryba, V., Mohamed, M., Nagi, A., Rashad Temerik, A., Elshawy, M. E., Mahmoud, M. I., Anwar, M., Rageh, T., Elmokadem, A., Gaballa, K., Teppo, S., Pengerma, P., Ballouhey, Q., Bergeat, D., Weyl, A., Hain, E., Gyedu, A., Yenli, E., Osei-Poku, D., Rompou, V. -A., Zoikas, A., Gaitanidis, A., Koukis, G., Perivoliotis, K., Tavlas, P., Galanos-Demiris, K., Zografos, G., Karavokyros, I., Xanthopoulou, G., Iordanidou, E., Ayau, F., Garcia, A., Damjan, P., Wason, D., B L, A., Rangganata, E., Kamath, P., O'Connor, D. B., Pinto, M., Perrone, F., Tropeano, F. P., Troilo, F., Bossi, D., Scala, D., Pulitano, L., Carella, M., Pietrabissa, A., Gori, A., Giraudo, G., De Simone, V., Russo, A. A., Braccio, B., Al-Taher, R., Athamneh, S., Parker, A., Sawiee, A., Kattia, A., Tababa, O., Shaeeb, Z., Syminas, V., Jurgaitis, J., Damuleviciene, G., Svagzdys, S., Razafimanjato, N. N. M., Chieng Loo, L., Tiong, I. C., Wan Muhmad, W. F., Vijeyan, H., Li Ying, T., Grech, G., Arrangoiz, R., Jimenez Ley, V. B., Arizpe, D., Lagunes Lara, E., Castro Lopez, E. V., Eaazim, J., Gordinou de Gouberville, M., Bastiaenen, V., Rottier, S., Nahab, F., Ji, M. Y., Seyoji, M., Nwachukwu, C., Emeghara, O., Muhammed, S. E., Idowu, A., Sowemimo, O., Ogundoyin, O., Akande, O., Lott, A., Nadeem, M., Laghari, A. A., Loya, A., Mushtaq, H., Abdullah, M. T., Abuhilal, B., Atawneh, M., Hamdan, H., Alhabil, B., Srour, A., Mousa, I., Da Silva Medina, L., Bartosiak, K., Ferreira, P., Francisco, V., Lemos, R., Frutuoso, L., Fernandes, S., Fonseca, T., Pereira, J., Rachadell, J., Torre, A., Madeira Martins, F., Carvalho, A. 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M., Srinivas, A., Sung, C. -Y., Tai, A., Valle Aranda, Y. C., Venturini, S., Wilguens Lartigue, J., Public and occupational health, AMS - Sports, APH - Health Behaviors & Chronic Diseases, CCA - Cancer Treatment and quality of life, Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, and Albarella, Sara
Subjects: global surgery, hospitals, humans, income, neoplasms, postoperative period, poverty, prospective studies, no keywords listed, General Medicine, Prospective Studie, Hospital, Settore MED/18 - Chirurgia Generale, outcome, Hospitals, Humans, Income, Neoplasms, surgery, Postoperative Period, Poverty, Prospective Studies, cancer surgery, Human, hospital facilities
Abstract: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p
Published: 2022
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18. Satura Resartus : Living in the Woods with Bears

Author: Critchley, Simon
Published: 2005
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19. Contesting Tradition: The Deep Play and Protest of Pigeon Shoots

Author: Bronner, Simon J.
Published: 2005

20. Ecosystem Collapse in Pleistocene Australia and a Human Role in Megafaunal Extinction

Author: Miller, Gifford H., Fogel, Marilyn L., Magee, John W., Gagan, Michael K., Clarke, Simon J., and Johnson, Beverly J.
Published: 2005

21. Comparison of Fine-Scale Recombination Rates in Humans and Chimpanzees

Author: Winckler, Wendy, Myers, Simon R., Richter, Daniel J., Onofrio, Robert C., McDonald, Gavin J., Bontrop, Ronald E., Gabriel, Stacey B., Reich, David, Donnelly, Peter, and Altshuler, David
Published: 2005

22. GC/AT-Content Spikes as Genomic Punctuation Marks

Author: Zhang, Lingang, Kasif, Simon, Cantor, Charles R., and Broude, Natalia E.
Published: 2004

23. Universal Shylockery: Money and Morality in "The Merchant of Venice"

Author: Critchley, Simon and McCarthy, Tom
Published: 2004

24. The Complete Genome Sequence of Mycobacterium bovis

Author: Garnier, Thierry, Eiglmeier, Karin, Camus, Jean-Christophe, Medina, Nadine, Mansoor, Huma, Pryor, Melinda, Duthoy, Stephanie, Grondin, Sophie, Lacroix, Celine, Monsempe, Christel, Simon, Sylvie, Harris, Barbara, Atkin, Rebecca, Doggett, Jon, Mayes, Rebecca, Keating, Lisa, Wheeler, Paul R., Parkhill, Julian, Barrell, Bart G., Cole, Stewart T., Gordon, Stephen V., and Hewinson, R. Glyn
Published: 2003

25. Balancing Selection at the Prion Protein Gene Consistent with Prehistoric Kurulike Epidemics

Author: Mead, Simon, Whitfield, Jerome, Beck, Jonathan A., Poulter, Mark, Campbell, Tracy, Uphill, James B., Goldstein, David, Alpers, Michael, and Collinge, John
Published: 2003

26. Mesenchymal stem cells and their use as cell replacement therapy and disease modelling tool

Author: García-Castro, J, Trigueros, C, Madrenas, J, Pérez-Simón, JA, Rodriguez, R, and Menendez, P
Subjects: Regenerative Medicine, Stem Cell Research, Stem Cell Research - Nonembryonic - Human, Transplantation, Biotechnology, Stem Cell Research - Nonembryonic - Non-Human, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Aetiology, 2.1 Biological and endogenous factors, Musculoskeletal, Animals, Clinical Trials as Topic, Disease, Humans, Immune Tolerance, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Models, Biological, mesenchymal stem cells, immune tolerance, cell replacement therapies, differentiation, neoplastic cell transformation, clinical trials, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology, Clinical Sciences, Biochemistry & Molecular Biology
Abstract: Mesenchymal stem cells (MSCs) from adult somatic tissues may differentiate in vitro and in vivo into multiple mesodermal tissues including bone, cartilage, adipose tissue, tendon, ligament or even muscle. MSCs preferentially home to damaged tissues where they exert their therapeutic potential. A striking feature of the MSCs is their low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes and antigen-presenting cells. Instead, MSCs appear to be immunosuppressive in vitro. Their multilineage differentiation potential coupled to their immuno-privileged properties is being exploited worldwide for both autologous and allogeneic cell replacement strategies. Here, we introduce the readers to the biology of MSCs and the mechanisms underlying immune tolerance. We then outline potential cell replacement strategies and clinical applications based on the MSCs immunological properties. Ongoing clinical trials for graft-versus-host-disease, haematopoietic recovery after co-transplantation of MSCs along with haematopoietic stem cells and tissue repair are discussed. Finally, we review the emerging area based on the use of MSCs as a target cell subset for either spontaneous or induced neoplastic transformation and, for modelling non-haematological mesenchymal cancers such as sarcomas.
Published: 2008

27. Human Gene Therapy: Genes without Frontiers?

Author: Simon, Eric J.
Published: 2002
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28. Anthrax: A Guide for Biology Teachers

Author: Simon, Eric J.
Published: 2002
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29. Creativity in the Arts and the Sciences

Author: Simon, Herbert A.
Published: 2001

30. Natural Selection and Quantitative Genetics of Life-History Traits in Western Women: A Twin Study

Author: Kirk, Katherine M., Blomberg, Simon P., Duffy, David L., Heath, Andrew C., and Martin, Nick G.
Published: 2001

31. Mitochondrial DNA Sequences in Ancient Australians: Implications for Modern Human Origins

Author: Adcock, Gregory J., Dennis, Elizabeth S., Easteal, Simon, Huttley, Gavin A., Jermiin, Lars S., Peacock, W. James, and Thorne, Alan
Published: 2001

32. Centering the Needs of Transgender, Nonbinary, and Gender-Diverse Populations in Neuroendocrine Models of Gender-Affirming Hormone Therapy

Author: Krisha Aghi, Teddy G. Goetz, Daniel R. Pfau, Simón(e) D. Sun, Troy A. Roepke, and Eartha Mae Guthman
Subjects: Translational Research, Biomedical, Cognitive Neuroscience, Humans, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Hormones, Biological Psychiatry
Abstract: Most studies attempting to address the health care needs of the millions of transgender, nonbinary, and/or gender-diverse (TNG) individuals rely on human subjects, overlooking the benefits of translational research in animal models. Researchers have identified many ways in which gonadal steroid hormones regulate neuronal gene expression, connectivity, activity, and function across the brain to control behavior. However, these discoveries primarily benefit cisgender populations. Research into the effects of exogenous hormones such as estradiol, testosterone, and progesterone has a direct translational benefit for TNG individuals on gender-affirming hormone therapies (GAHTs). Despite this potential, endocrinological health care for TNG individuals remains largely unimproved. Here, we outline important areas of translational research that could address the unique health care needs of TNG individuals on GAHT. We highlight key biomedical questions regarding GAHT that can be investigated using animal models. We discuss how contemporary research fails to address the needs of GAHT users and identify equitable practices for cisgender scientists engaging with this work. We conclude that if necessary and important steps are taken to address these issues, translational research on GAHTs will greatly benefit the health care outcomes of TNG people.
Published: 2022
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33. SF3B1, RUNX1 and TP53 Mutations Significantly Impact the Outcome of Patients With Lower-Risk Myelodysplastic Syndrome

Author: Jose F, Falantes, Francisco J, Márquez-Malaver, Estrella, Carrillo, Marta García, Culebras, Rosario, Morales, Concepción, Prats, Maria T, Vargas, Teresa, Caballero, Eduardo, Rodríguez-Arbolí, Ildefonso, Espigado, and Jose Antonio, Pérez-Simón
Subjects: Cancer Research, Myelodysplasia, Leukemia, Myelomonocytic, Chronic, Hematology, Phosphoproteins, Prognosis, Oncology, Myelodysplastic Syndromes, Core Binding Factor Alpha 2 Subunit, Mutation, Genetics, Humans, RNA Splicing Factors, Leukemic progression, Tumor Suppressor Protein p53
Abstract: [Introduction] Prognosis of patients with myelodysplastic syndrome (MDS), particularly the group with lower-risk disease (LR-MDS) is very heterogeneous. Several studies have described the prognostic value of recurrent somatic mutations in MDS including all risk categories. Recently, the incorporation of genomic data to clinical parameters defined the new Molecular International Prognostic Scoring System (IPSS-M)., [Materials and Methods] In this study, we evaluated the impact of molecular profile in a series of 181 patients with LR-MDS and non-proliferative chronic myelomonocytic leukemia., [Results] Epigenetic regulators (TET2, ASXL1) and splicing (SF3B1) were the most recurrent mutated pathways. In univariate analysis, RUNX1 or TP53 mutations correlated with lower median overall survival (OS). In contrast, SF3B1 mutation was associated with prolonged median OS [95 months (95% IC, 32-157) vs. 33 months (95% CI, 19-46) in unmutated patients (P < 0.01)]. In a multivariate Cox regression model, RUNX1 mutations independently associated with shorter OS, while SF3B1 mutation retained its favorable impact on outcome (HR: 0.24, 95% CI, 0.1-0.5; P = 0.001). In addition, TP53 or RUNX1 mutations were identified as predictive covariates for the probability of leukemic progression (P < 0.001)., [Conclusion] Incorporation of molecular testing in LR-MDS identified a subset of patients with expected poorer outcome, either due to lower survival or probability of leukemic progression.
Published: 2022
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34. Cell-free fetal DNA testing performance and fetal fraction estimation are not affected in ART-conceived pregnancies

Author: Nuria Balaguer, Emilia Mateu-Brull, María Gómez-López, Carlos Simón, and Miguel Milán
Subjects: Reproductive Medicine, Pregnancy, Case-Control Studies, Prenatal Diagnosis, Rehabilitation, Humans, Obstetrics and Gynecology, Female, DNA, Aneuploidy, Cell-Free Nucleic Acids
Abstract: STUDY QUESTION Does ART-based conception influence fetal fraction (FF) estimation and cell-free fetal DNA (cffDNA) testing performance? SUMMARY ANSWER Mode of conception (ART versus natural) does not impact FF estimation or cffDNA test informativity rates. WHAT IS KNOWN ALREADY Pregnancies achieved via ART are increasing, and cffDNA testing is displacing traditional prenatal screening methods due to its high sensitivity and specificity and noninvasive nature. However, conflicting data exist on cffDNA testing performance and FF in ART pregnancies compared with natural pregnancies. STUDY DESIGN, SIZE, DURATION We performed a case-control study that included 21 558 consecutive pregnancies (spontaneous, n = 15 707; ART, n = 5851). ART-conceived pregnancies were stratified into two groups according to oocyte origin. Samples were collected from April 2015 to September 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS The study included women from different centers worldwide. Blood samples were drawn from the 10th week of gestation onward. Massive parallel whole-genome sequencing was used to analyze cffDNA content in blood plasma. Two different types of technologies (single-end and paired-end) were applied because of analysis technology changes made by the sequencing provider over time. FF was determined using different methods depending on the type of technology used. Cases with an FF 35 or MAIN RESULTS AND THE ROLE OF CHANCE A univariate t-test demonstrated no significant differences in FF values between ART (median FF = 9.2%) and spontaneous pregnancies (median FF = 9.2%). Also, a multivariate analysis showed that the mode of conception, did not strongly impact the percentage of FF. ART-treated women showed a lower incidence of high-risk cffDNA results compared to women who conceived naturally, specifically for trisomy (T)21 (0.7% versus 1.3%, P = 0.001) and T18 (0.1% versus 0.3%, P = 0.001). A multivariate model stratified by type of aneuploidy suggested that these differences were conditioned by oocyte origin, especially for the T21 risk classification (P LIMITATIONS, REASONS FOR CAUTION Our study lacks follow-up data for low- and high-risk cases of both ART-conceived and naturally conceived pregnancies. Therefore, the results comparing FPR in both populations should be interpreted carefully. Also, collecting information about different ART modalities and regarding preimplantation genetic testing for aneuploidy treatments would help draw definite explanations for the trends observed in this study. WIDER IMPLICATIONS OF THE FINDINGS This is the first study that demonstrates, with a large sample size, that FF is not influenced by mode of conception, demystifying the notion that patients undergoing ART have a higher probability of noninformative cffDNA testing results. Multivariate models stratified by oocyte origin and type of aneuploidy demonstrated that ART-conceived pregnancies do not have a higher probability of classification as a high-risk pregnancy in prenatal testing. This information is especially valuable to clinicians and genetic counselors when informing patients about the risks and limitations of cffDNA testing in ART pregnancies. STUDY FUNDING/COMPETING INTEREST(S) This study was financially supported by Igenomix Lab S.L.U. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.
Published: 2022
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35. Clinical Impact of Genetic Diagnosis of Sensorineural Hearing Loss in Adults

Author: Patricia Corriols-Noval, Eugenia Carmela López Simón, Juan Cadiñanos, Marta Diñeiro, Raquel Capín, Rocío González Aguado, María Costales Marcos, Carmelo Morales Angulo, and Rubén Cabanillas Farpón
Subjects: Adult, Hearing Loss, Sensorineural, High-Throughput Nucleotide Sequencing, Deafness, Cataract, Monoacylglycerol Lipases, Sensory Systems, Otorhinolaryngology, Mutation, Trans-Activators, Humans, Intercellular Signaling Peptides and Proteins, Neurology (clinical), Hearing Loss
Abstract: Adult genetic sensorineural hearing loss (SNHL) may be underestimated.The diagnosis of genetic hearing loss is challenging, given its extreme genetic and phenotypic heterogeneity, particularly in adulthood. This study evaluated the utility of next-generation sequencing (NGS) in the etiological diagnosis of adult-onset SNHL.Adults (16 yr old) with SNHL were recruited at the Otolaryngology Department at Marqués de Valdecilla University Hospital (Spain). Environmental factors, acoustic trauma, endolymphatic hydrops, and age-related hearing loss were excluding criteria. An NGS gene panel was used, including 196 genes (OTOgenics v3) or 229 genes (OTOgenics v4) related to syndromic and nonsyndromic hearing loss.Sixty-five patients were included in the study (average age at the onset of SNHL, 41 yr). Fifteen pathogenic/likely pathogenic variants considered to be causative were found in 15 patients (23% diagnostic yield) in TECTA (4), KCNQ4 (3), GJB2 (2), ACTG1 (1), COL2A1 (1), COCH (1), COCH/COL2A1 (1), STRC (1), and ABHD12 (1). Three patients had syndromic associations (20% of patients with genetic diagnosis) that had not been previously diagnosed (two Stickler type I and one polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, cataract syndrome). Seven variants of unknown significance were found in COL11A1 (1), GSMDE (2), DNTM1 (1), SOX10 (1), EYA4 (1), and TECTA (1).NGS gene panels can provide diagnostic yields greater than 20% for adult SNHL, with a significant proportion of variant of unknown significance that could potentially contribute to increasing diagnostic output. Identifying a genetic cause enables genetic counseling, provides prognostic information and can reveal unrecognized syndromes contributing to an accurate management of their associated manifestations.
Published: 2022
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36. Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis

Author: Fielding, Claire, García-García, Andrés, Korn, Claudia, Gadomski, Stephen, Fang, Zijian, Reguera, Juan L, Pérez-Simón, José A, Gottgens, Berthold, Méndez-Ferrer, Simón, National Institutes of Health (US), International Scholarship at The University of Cambridge, European Commission, European Research Council, MRC Cambridge Stem Cell Institute, National Health Institute Blood and Transplant (UK), Cancer Research UK, Wellcome Trust, García-García, Andrés [0000-0002-8797-649X], Pérez-Simón, José A [0000-0003-3616-6101], Göttgens, Berthold [0000-0001-6302-5705], Méndez-Ferrer, Simón [0000-0002-9805-9988], Apollo - University of Cambridge Repository, Universidad de Sevilla. Departamento de Medicina, and Gottgens, Berthold [0000-0001-6302-5705]
Subjects: Glial Cell Line-Derived Neurotrophic Factor Receptors, Science, Cholinergic Agents, General Physics and Astronomy, 13/106, Haematopoietic stem, General Biochemistry, Genetics and Molecular Biology, 631/532/2139, 13/1, Mice, 13/100, Bone Marrow, Risk Factors, 631/443/63, Animals, Humans, 14/19, Bone, 49/91, 631/532/2118/1542, Multidisciplinary, Cambridge Stem Cell Institute, Haematopoietic stem cells, article, Hematopoietic Stem Cell Transplantation, Mesenchymal Stem Cells, General Chemistry, Hematopoietic Stem Cells, Chemokine CXCL12, Hematopoiesis, 13/31, Cholinergic signals, Receptors, Adrenergic, beta-3, 13/51, 14/63, 692/499, Stem-cell niche, Regenerative haematopoiesis
Abstract: The sympathetic nervous system has been evolutionary selected to respond to stress and activates haematopoietic stem cells via noradrenergic signals. However, the pathways preserving haematopoietic stem cell quiescence and maintenance under proliferative stress remain largely unknown. Here we found that cholinergic signals preserve haematopoietic stem cell quiescence in bone-associated (endosteal) bone marrow niches. Bone marrow cholinergic neural signals increase during stress haematopoiesis and are amplified through cholinergic osteoprogenitors. Lack of cholinergic innervation impairs balanced responses to chemotherapy or irradiation and reduces haematopoietic stem cell quiescence and self-renewal. Cholinergic signals activate α7 nicotinic receptor in bone marrow mesenchymal stromal cells leading to increased CXCL12 expression and haematopoietic stem cell quiescence. Consequently, nicotine exposure increases endosteal haematopoietic stem cell quiescence in vivo and impairs hematopoietic regeneration after haematopoietic stem cell transplantation in mice. In humans, smoking history is associated with delayed normalisation of platelet counts after allogeneic haematopoietic stem cell transplantation. These results suggest that cholinergic signals preserve stem cell quiescence under proliferative stress., The sympathetic nervous system has been shown to respond to stress and activate haematopoietic stem cells. Here they show that cholinergic signals in the bone marrow preserve haematopoietic stem cell quiescence and self-renewal under proliferative stress.
Published: 2022
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37. Public Administration in Today's World of Organizations and Markets

Author: Simon, Herbert A.
Published: 2000
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38. Forum on Literatures of the Environment

Author: Arnold, Jean, Buell, Lawrence, Cohen, Michael P., Dodd, Elizabeth, Estok, Simon C., Heise, Ursula K., Levin, Jonathan, Murphy, Patrick D., Parra, Andrea, Slaymaker, William, Slovic, Scott, Sweet, Timothy, and Westling, Louise
Published: 1999
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39. Clustering of Non-Major Histocompatibility Complex Susceptibility Candidate Loci in Human Autoimmune Diseases

Author: Becker, Kevin G., Simon, Richard M., Bailey-Wilson, Joan E., Freidlin, Boris, Biddison, William E., McFarland, Henry F., and Trent, Jeffrey M.
Published: 1998

40. Why Public Administration?

Author: Simon, Herbert A.
Published: 1998

41. Maternal exome analysis for the diagnosis of oocyte maturation defects and early embryonic developmental arrest

Author: Antonio Capalbo, Silvia Buonaiuto, Matteo Figliuzzi, Gianluca Damaggio, Laura Girardi, Silvia Caroselli, Maurizio Poli, Cristina Patassini, Murat Cetinkaya, Beril Yuksel, Ajuna Azad, Marie Louise Grøndahl, Eva R. Hoffmann, Carlos Simón, Vincenza Colonna, and Semra Kahraman
Subjects: Exome sequencing, Obstetrics and Gynecology, Cell Cycle Proteins, Embryo development, Mice, Abnormal fertilization, Genetics of infertility, Oogenesis, Reproductive Medicine, Tubulin, Exome Sequencing, Oocyte maturation, Oocytes, ATPases Associated with Diverse Cellular Activities, Animals, Humans, Exome, Female, Infertility, Female, Developmental Biology
Abstract: Research question: Can a methodology be developed for case selection and whole-exome sequencing (WES) analysis of women who are infertile owing to recurrent oocyte maturation defects (OOMD) and/or preimplantation embryo lethality (PREMBL)? Design: Data were collected from IVF patients attending the Istanbul Memorial Hospital (2015–2021). A statistical methodology to identify infertile endophenotypes (recurrent low oocyte maturation rate, low fertilization rate and preimplantation developmental arrest) was developed using a large IVF dataset (11,221 couples). Twenty-eight infertile women with OOMD/PREMBL were subsequently enrolled for WES on their genomic DNA. Pathogenic variants were prioritized using a custom-made bioinformatic pipeline set to minimize false-positive discoveries through resampling in control cohorts (the Human Genome Diversity Project and 1343 whole-exome sequences from oocyte donors). Individual single-cell RNA sequencing data from 18 human metaphase II (MII) oocytes and antral granulosa cells was used for genome-wide validation. WES and bioinformatics were performed at Igenomix and the National Research Council, Italy. Results: Variant prioritization analysis identified 265 unique variants in 248 genes (average 22.4 per sample). Of the genes harbouring high-impact variants 78% were expressed by MII oocytes and/or antral granulosa cells, significantly higher than for random sample of controls (odds ratio = 5, Fisher's exact P = 0.0004). Seven of the 28 women (25%) were homozygous carriers of missense pathogenic variants in known candidate genes for OOMD/PREMBL, including PATL2, NLRP5 (n = 2),TLE6, PADI6, TUBB8 and TRIP13. Furthermore, novel gene–disease associations were identified. In fact, one woman with a low oocyte maturation rate was a homozygous carrier of high-impact variants in ENSA, an essential gene for prophase I meiotic transition in mice. Conclusions: This analytical framework could reveal known and new genes associated with isolated recurrent OOMD/PREMBL, providing essential indications for scaling this strategy to larger studies.
Published: 2022
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42. Estimation of the QTc interval in the presence of right bundle branch block: A comparative study using validated formulae for left bundle branch block

Author: Eusebio García-Izquierdo, Sergio García-Gómez, Cristina Aguilera-Agudo, Daniel De Castro-Campos, Daniel García-Rodríguez, Lourdes Fajardo-Simón, Darwin Veloza-Urrea, Melodie Segura-Domínguez, Diego Jiménez-Sánchez, Victor Castro-Urda, Jorge Toquero-Ramos, and Ignacio Fernández-Lozano
Subjects: Electrocardiography, Bundle-Branch Block, Humans, Reproducibility of Results, Cardiology and Cardiovascular Medicine
Abstract: Adequate measurement of the QT interval is of clinical importance in order to identify patients at higher risk for ventricular arrhythmias. Previous studies have described different methods to estimate baseline QT in patients with left bundle branch block (LBBB). However, the evidence regarding the assessment of the QT in patients with right bundle branch block (RBBB) is scarce.To analyze the feasibility and reliability of the different formulae described for LBBB in the estimation of the baseline QT in the presence of RBBB.We performed an observational study including patients who underwent electrophysiology study and/or ablation. Two types of RBBB were considered: 1) pacing-induced and 2) transient true RBBB. QRS, JT and QT intervals were measured during baseline and RBBB. Estimated QTc was calculated using LBBB formulae: Bogossian, Rautaharju, Tabatabaei, Tang-Rabkin, Yankelson, Wang. Linear correlation and intraclass correlation coefficients (ICC) were used to assess the reliability of these formulae for the estimation of baseline QTc.We finally included a total of 100 patients. Correlations between baseline and estimated QTc were strong (R 0.7) for all the formulae except for Tabatabaei. Yankelson and Wang showed the highest reliability (ICC = 0.775 and 0.727, respectively). Yankelson appeared to be the most accurate formula, with a mean estimated QTc closest to baseline values.Previously described formulae for LBBB exhibited marked differences regarding reliability in the estimation of the QTc interval in the presence of RBBB. According to our results, Yankelson showed the most consistent and accurate agreement in this setting.
Published: 2022
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43. Impact of neoadjuvant therapy on postoperative complications in non-small-cell lung cancer patients subjected to anatomic lung resection

Author: Alberto Cabañero Sánchez, Gemma María Muñoz Molina, Sara Fra Fernández, Alfonso Muriel García, Angel Cilleruelo Ramos, Néstor Martínez Hernández, Florentino Hernando Trancho, Nicolás Moreno Mata, Borja Aguinagalde de Valiente, Sergio Amor Alonso, Miguel Jesús Arrarás, Ana Isabel Blanco Orozco, Marc Boada Collado, Sergio Bolufer Nadal, Isabel Cal Vázquez, Sergi Call Caja, Ángel Cilleruelo Ramos, Miguel Congregado Loscertales, Silvana Crowley Carrasco, Raúl Embún Flor, Elena Fernández Martín, Juan José Fibla Alfara, Santiago García Barajas, Maria Dolores García Jiménez, Jose María García Prim, Jose Alberto García Salcedo, Carlos Fernando Giraldo Ospina, David Gómez de Antonio, María Teresa Gómez Hernández, Juan José Gelbenzu Zazpe, Jorge Henández Ferrández, Jennifer D. Illana Wolf, Alberto Jauregui Abularach, Marcelo Jiménez López, Unai Jiménez Maestre, Cipriano López García, Iker López Sanz, Elisabeth Martínez Téllez, Lucía Milla Collado, Roberto Mongil Poce, Francisco Javier Moradiellos Díez, Ramón Moreno Balsalobre, Sergio B. Moreno Merino, Carme Obiols Fornell, Florencio Quero Valenzuela, María Elena Ramírez Gil, Ricard Ramos Izquierdo, José Luis Recuero Díaz, Eduardo Rivo Vázquez, Alberto Rodríguez Fuster, Rafael Rojo Marcos, Iñigo Royo Crespo, David Sánchez Lorente, Laura Sanchez Moreno, Julio Sesma Romero, Carlos Simón Adiego, and Juan Carlos Trujillo Reyes
Subjects: Lung Neoplasms, Postoperative Complications, Treatment Outcome, Oncology, Carcinoma, Non-Small-Cell Lung, Humans, Surgery, Chemoradiotherapy, General Medicine, Pneumonectomy, Lung, Neoadjuvant Therapy
Abstract: To study the impact of neoadjuvant therapies on postoperative complications and mortality among non-small-cell lung cancer (NSCLC) patients subjected to anatomic lung resection and included in the Spanish cohort of the video-assisted thoracic surgery (GE-VATS) multicenter database.The study included a total of 3085 patients from 33 centers between December 2016 and March 2018. We performed a comparative analysis of the complications and mortality in patients who received neoadjuvant therapies (n = 263) versus those who did not (n = 2822). A propensity score-matched analysis was used to adjust for potential confounders. Association between exposure in two groups and outcomes were estimated by logistic regression weighted by inverse of probability of receiving the treatment that actually received.In the unadjusted analysis, the chemotherapy (CT) and chemoradiotherapy (CRT) group presented a higher frequency of ICU readmissions, reinterventions, empyema, cardiovascular complications, a greater frequency of atrial fibrillation, and an increased need for blood product transfusions. In the adjusted group, CT and CRT patients had a higher rate of cardiovascular complications (CT p = 0.002; OR 2.29; 95% CI 1.34-3.94 and CRT p = 0.001; OR 2.90; 95% CI 1.52-5-52), arrhythmias (CT p = 0.013; OR 2.23; 95% CI 1.18-4.20 and CRT p = 0.046; OR 2.22; 95% CI 1.01-4.90) and transfussions (CT p = 0.042; OR 2.95; 95% CI 1.04-8.35 and CRT p 0.001; OR 7.74; 95% CI 3.01-19-92).Based on our series, neoadjuvant CT and CRT were associated with a higher rate of cardiovascular complications, arrhythmias and transfussions in patients with NSCLC subjected to anatomic lung resection.
Published: 2022
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44. Results of a survey on the treatment of adolescents and young adult (AYA) sarcoma patients in Spain at present time

Author: Cristina Mata Fernández, Nacho Gutierrez Carrasco, Antonio Juan Ribelles, Nadia Hindi Muñiz, Anna Estival González, Alba Rubio San Simón, Lucía Castillo Portellano, Sofía Ruiz Medina, and Claudia Valverde Morales
Subjects: Osteosarcoma, Cancer Research, Adolescent, Bone Neoplasms, Sarcoma, Soft Tissue Neoplasms, General Medicine, Young Adult, Oncology, Spain, Neoplasms, Humans, Neoplasm Recurrence, Local, Child
Abstract: We aimed to analyse health care services for adolescents and young adults (AYA) with sarcomas in Spain.A survey was sent to all Spanish cancer centres, including questions about demographic, facilities, and treatment strategies for AYAs with sarcomas in the last 2 years.Thirty-five units participated in the survey, 17 paediatric and 15 adult units. There were three specialized AYA units. First line regimen varied depending on whether the treating unit was paediatric or not, for osteosarcomas, rhabdomyosarcomas, and non-rhabdomyosarcomas. By contrast, 91.4% of Ewing sarcomas were treated according to EE2012. In the relapse setting, differences between units were higher in all tumours. Additionally, 48% of the units reported not having trials for this population.There are major differences in the treatment of AYAs with sarcomas between adult and paediatric units. Enormous efforts are needed to homogenize treatments and increase the access to innovation.
Published: 2022
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45. BNIP3 Is Involved in Muscle Fiber Atrophy in Late-Onset Pompe Disease Patients

Author: Ana Carrasco-Rozas, Esther Fernández-Simón, Xavier Suárez-Calvet, Patricia Piñol-Jurado, Jorge Alonso-Pérez, Noemí de Luna, Benedikt Schoser, Peter Meinke, Cristina Domínguez-González, Aurelio Hernández-Laín, Carmen Paradas, Eloy Rivas, Isabel Illa, Montse Olivé, Eduard Gallardo, and Jordi Díaz-Manera
Subjects: Glycogen Storage Disease Type II, Proto-Oncogene Proteins, TOR Serine-Threonine Kinases, Muscle Fibers, Skeletal, Humans, Membrane Proteins, Atrophy, Proto-Oncogene Proteins c-akt, Pathology and Forensic Medicine
Abstract: Late-onset Pompe disease (LOPD) is a rare genetic disorder produced by mutations in the GAA gene and is characterized by progressive muscle weakness. LOPD muscle biopsies show accumulation of glycogen along with the autophagic vacuoles associated with atrophic muscle fibers. The expression of molecules related to muscle fiber atrophy in muscle biopsies of LOPD patients was studied using immunofluorescence and real-time PCR. BCL2 and adenovirus E1B 19-kDa interacting protein 3 (BNIP3), a well-known atrogene, was identified as a potential mediator of muscle fiber atrophy in LOPD muscle biopsies. Vacuolated fibers in LOPD patient muscle biopsies were smaller than nonvacuolated fibers and expressed BNIP3. The current data suggested that BNIP3 expression is regulated by inhibition of the AKT-mammalian target of rapamycin pathway, leading to phosphorylation of Unc-51 like autophagy activating kinase 1 (ULK1) at Ser317 by AMP-activated protein kinase. Myoblasts and myotubes obtained from LOPD patients and age-matched controls were studied to confirm these results using different molecular techniques. Myotubes derived from LOPD patients were likewise smaller and expressed BNIP3. Conclusively, transfection of BNIP3 into control myotubes led to myotube atrophy. These findings suggest a cascade that starts with the inhibition of the AKT-mammalian target of rapamycin pathway and activation of BNIP3 expression, leading to progressive muscle fiber atrophy. These results open the door to potential new treatments targeting BNIP3 to reduce its deleterious effects on muscle fiber atrophy in Pompe disease.
Published: 2022
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46. Intracranial arachnoid cysts and epilepsy in children: Should this be treated surgically? Our 29-year experience and review of the literature

Author: Juan Pablo García-Iñiguez, Javier Orduna Martínez, Miguel Lafuente Hidalgo, Beatriz Curto Simón, Javier López Pisón, and Pilar Samper Villagrasa
Subjects: Pediatrics, medicine.medical_specialty, Age at diagnosis, Asymptomatic, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Medicine, Humans, Epilepsy surgery, Cyst, Prospective Studies, Prospective cohort study, Child, Retrospective Studies, business.industry, General Medicine, medicine.disease, Intracranial Arachnoid Cysts, Arachnoid Cysts, Epilepsy in children, Surgery, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Introduction and objective Arachnoid cysts (ACs) are relatively frequent lesions related to different neurological symptoms, being mostly incidentally diagnosed. This study aims to clarify whether AC surgery in epileptic patients is useful in their treatment. Material and methods The patients registered in the database of the Neuropediatrics Section from May 1990 to August 2019 are analyzed retrospectively. Patients in whom the diagnosis of ACs and epilepsy coincide are studied. The location, size and number of ACs, neurological development, age at diagnosis, follow-up time, the performance of surgery on the cyst, evolution, anatomical relationship between brain electrical activity and location of AC, and type of epilepsy are analyzed. Results After analyzing the database, we found 1881 patients diagnosed with epilepsy, of which 25 had at least one intracranial AC. In 9 of the patients, cerebral or genetic pathologies were the cause of epilepsy. Of the other 16, only 2 patients showed that the type of epilepsy and the epileptogenic focus coincided with the location of the AC; one of them was surgically treated without success, and the other one remained asymptomatic without receiving medical or surgical treatment. Conclusions Although it is necessary to design a prospective study to establish causality, the results of our research and the available literature suggest that there is no causal relationship between the presence of ACs and epilepsy. The study and treatment of these patients should be carried out in a multidisciplinary epilepsy surgery unit, without initially assuming that the AC is the cause of epilepsy.
Published: 2022
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47. Rejoinder: Situative versus Cognitive Perspectives: Form versus Substance

Author: Anderson, John R., Reder, Lynne M., and Simon, Herbert A.
Published: 1997

48. Human Rights and the Rights of States: Terry Nardin on Nonintervention

Author: Caney, Simon
Published: 1997

49. I Rather Think I Am a Darwinian

Author: Blackburn, Simon
Published: 1996

50. Estimating the Age of the Common Ancestor of Men from the ZFY Intron

Author: Fu, Yun-Xin, Li, Wen-Hsiung, Donnelly, Peter, Tavaré, Simon, Balding, David J., Griffith, Robert C., Weiss, Gunter, von Haeseler, Arndt, Rogers, Jeffrey, Samollow, Paul B., Comuzzie, Anthony G., Dorit, Robert L., Akashi, Hiroshi, and Gilbert, Walter
Published: 1996

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