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- IgG Antibody responses to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Their effective potential for disease diagnosis and pathological antigenic mimicryPublication . Fonseca, André; Szysz, Mateusz; Ly, Hoang Thien; Cordeiro, Clara; Sepúlveda, NunoThe diagnosis and pathology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain under debate. However, there is a growing body of evidence for an autoimmune component in ME/CFS caused by the Epstein-Barr virus (EBV) and other viral infections. Materials and Methods: In this work, we analyzed a large public dataset on the IgG antibodies to 3054 EBV peptides to understand whether these immune responses could help diagnose patients and trigger pathological autoimmunity; we used healthy controls (HCs) as a comparator cohort. Subsequently, we aimed at predicting the disease status of the study participants using a super learner algorithm targeting an accuracy of 85% when splitting data into train and test datasets. Results: When we compared the data of all ME/CFS patients or the data of a subgroup of those patients with non-infectious or unknown disease triggers to the data of the HC, we could not find an antibody-based classifier that would meet the desired accuracy in the test dataset. However, we could identify a 26-antibody classifier that could distinguish ME/CFS patients with an infectious disease trigger from the HCs with 100% and 90% accuracies in the train and test sets, respectively. We finally performed a bioinformatic analysis of the EBV peptides associated with these 26 antibodies. We found no correlation between the importance metric of the selected antibodies in the classifier and the maximal sequence homology between human proteins and each EBV peptide recognized by these antibodies. Conclusions: In conclusion, these 26 antibodies against EBV have an effective potential for disease diagnosis in a subset of patients. However, the peptides associated with these antibodies are less likely to induce autoimmune B-cell responses that could explain the pathogenesis of ME/CFS.
- Self-reported quality care for knee osteoarthritis: comparisons across Denmark, Norway, Portugal and the UKPublication . Osteras, N.; Jordan, K. P.; Clausen, B.; Cordeiro, C.; Dziedzic, K.; Edwards, J.; Gronhaug, G.; Higginbottom, A.; Lund, H.; Pacheco, G.; Pais, S.; Hagen, K. B.Objectives: To assess and compare patient perceived quality of osteoarthritis (OA) management in primary healthcare in Denmark, Norway, Portugal and the UK. Methods: Participants consulting with clinical signs and symptoms of knee OA were identified in 30 general practices and invited to complete a cross-sectional survey including quality indicators (QI) for OA care. A QI was considered as eligible if the participant had checked 'Yes' or 'No', and as achieved if the participant had checked 'Yes' to the indicator. The median percentage (with IQR and range) of eligible QIs achieved by country was determined and compared in negative binominal regression analysis. Achievement of individual QIs by country was determined and compared using logistic regression analyses. Results: A total of 354 participants self-reported QI achievement. The median percentage of eligible QIs achieved (checked 'Yes') was 48% (IQR 28%, 64%; range 0-100%) for the total sample with relatively similar medians across three of four countries. Achievement rates on individual QIs showed a large variation ranging from 11% (referral to services for losing weight) to 67% (information about the importance of exercise) with significant differences in achievement rates between the countries. Conclusions: The results indicated a potential for improvement in OA care in all four countries, but for somewhat different aspects of OA care. By exploring these differences and comparing healthcare services, ideas may be generated on how the quality might be improved across nations. Larger studies are needed to confirm and further explore the findings.
- Hybrid nanosystems based on natural polymers as protein carriers for respiratory delivery: stability and toxicological evaluationPublication . Rodrigues, Susana; Cordeiro, Clara; Seijo, Begona; Remunan-Lopez, Carmen; Grenha, AnaChitosan/carrageenan/tripolyphosphate nanoparticles were previously presented as holding potential for an application in transmucosal delivery of macromolecules, with tripolyphosphate demonstrating to contribute for both size reduction and stabilisation of the nanoparticles. This work was aimed at evaluating the capacity of the nanoparticles as protein carriers for pulmonary and nasal transmucosal delivery, further assessing their biocompatibility pattern regarding that application. Nanoparticles demonstrated stability in presence of lysozyme, while freeze-drying was shown to preserve their characteristics when glucose or sucrose were used as cryoprotectants. Bovine serum albumin was associated to the nanoparticles, which were successfully microencapsulated by spray-drying to meet the aerodynamic requirements inherent to pulmonary delivery. Finally, a satisfactory biocompatibility profile was demonstrated upon exposure of two respiratory cell lines (Calu-3 and A549 cells) to the carriers. A negligible effect on cell viability along with no alterations on transepithelial electrical resistance and no induction of inflammatory response were observed. (C) 2015 Elsevier Ltd. All rights reserved.
- The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression dataPublication . Malato, João; Sotzny, Franziska; Bauer, Sandra; Freitag, Helma; Fonseca, André; Grabowska, Anna D.; Graça, Luís; Cordeiro, Clara; Nacul, Luís; Lacerda, Eliana M.; Castro-Marrero, Jesus; Scheibenbogen, Carmen; Westermeier, Francisco; Sepúlveda, NunoPeople with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often report a high frequency of viral infections and flu-like symptoms during their disease course. Given that this reporting agrees with different immunological abnormalities and altered gene expression profiles observed in the disease, we aimed at answering whether the expression of the human angiotensin-converting enzyme 2 (ACE2), the major cell entry receptor for SARS-CoV-2, is also altered in these patients. In particular, a low expression of ACE2 could be indicative of a high risk of developing COVID-19. We then performed a meta-analysis of public data on CpG DNA methylation and gene expression of this enzyme and its homologous ACE protein in peripheral blood mononuclear cells and related subsets. We found that patients with ME/CFS have decreased methylation levels of four CpG probes in the ACE locus (cg09920557, cg19802564, cg21094739, and cg10468385) and of another probe in the promoter region of the ACE2 gene (cg08559914). We also found a decreased expression of ACE2 but not of ACE in patients when compared to healthy controls. Accordingly, in newly collected data, there was evidence for a significant higher proportion of samples with an ACE2 expression below the limit of detection in patients than healthy controls. Altogether, patients with ME/CFS can be at a higher COVID-19 risk and, if so, they should be considered a priority group for vaccination by public health authorities. To further support this conclusion, similar research is rec ommended for other human cell entry receptors and cell types, namely, those cells targeted by the virus.
- Antibody selection strategies and their impact in predicting clinical malaria based on multi-sera dataPublication . Fonseca, André; Spytek, Mikolaj; Biecek, Przemysław; Cordeiro, Clara; Sepúlveda, NunoNowadays, the chance of discovering the best antibody candidates for predicting clinical malaria has notably increased due to the availability of multi-sera data. The analysis of these data is typically divided into a feature selection phase followed by a predictive one where several models are constructed for predicting the outcome of interest. A key question in the analysis is to determine which antibodies should be included in the predictive stage and whether they should be included in the original or a transformed scale (i.e. binary/dichotomized).
- Revisiting IgG antibody reactivity to epstein-barr virus in myalgic encephalomyelitis/chronic fatigue syndrome and Its potential application to disease diagnosisPublication . Sepúlveda, Nuno; Malato, João; Sotzny, Franziska; Grabowska, Anna D.; Fonseca, André; Cordeiro, Clara; Graça, Luís; Biecek, Przemyslaw; Behrends, Uta; Mautner, Josef; Westermeier, Francisco; Lacerda, Eliana M.; Scheibenbogen, CarmenInfections by the Epstein-Barr virus (EBV) are often at the disease onset of patients suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, serological analyses of these infections remain inconclusive when comparing patients with healthy controls (HCs). In particular, it is unclear if certain EBV-derived antigens eliciting antibody responses have a biomarker potential for disease diagnosis. With this purpose, we re-analyzed a previously published microarray data on the IgG antibody responses against 3,054 EBV-related antigens in 92 patients with ME/CFS and 50 HCs. This re-analysis consisted of constructing different regression models for binary outcomes with the ability to classify patients and HCs. In these models, we tested for a possible interaction of different antibodies with age and gender. When analyzing the whole data set, there were no antibody responses that could distinguish patients from healthy controls. A similar finding was obtained when comparing patients with non-infectious or unknown disease trigger with healthy controls. However, when data analysis was restricted to the comparison between HCs and patients with a putative infection at their disease onset, we could identify stronger antibody responses against two candidate antigens (EBNA4_0529 and EBNA6_0070). Using antibody responses to these two antigens together with age and gender, the final classification model had an estimated sensitivity and specificity of 0.833 and 0.720, respectively. This reliable case-control discrimination suggested the use of the antibody levels related to these candidate viral epitopes as biomarkers for disease diagnosis in this subgroup of patients. To confirm this finding, a follow-up study will be conducted in a separate cohort of patients.
- Using satellite-based data to facilitate consistent monitoring of the marine environment around IrelandPublication . Casal, Gema; Cordeiro, Clara; McCarthy, TimAs an island nation, Ireland needs to ensure effective management measures to protect marine ecosystems and their services, such as the provision of fishery resources. The characterization of marine waters using satellite data can contribute to a better understanding of variations in the upper ocean and, consequently, the effect of their changes on species populations. In this study, nineteen years (1998–2016) of monthly data of essential climate variables (ECVs), chlorophyll (Chl-a), and the diffuse attenuation coefficient (K490) were used, together with previous analyses of sea surface temperature (SST), to investigate the temporal and spatial variability of surface waters around Ireland. The study area was restricted to specific geographically delineated divisions, as defined by the International Council of the Exploration of the Seas (ICES). The results showed that SST and Chl-a were positively and significantly correlated in ICES divisions corresponding to oceanic waters, while in coastal divisions, SST and Chl-a showed a significant negative correlation. Chl-a and K490 were positively correlated in all cases, suggesting an important role of phytoplankton in light attenuation. Chl-a and K490 had significant trends in most of the divisions, reaching maximum values of 1.45% and 0.08% per year, respectively. The strongest seasonal Chl-a trends were observed in divisions VIId and VIIe (the English Channel), primarily in the summer months, followed by northern divisions VIa (west of Scotland) and VIb (Rockall) in the winter months.
- Forecasting: theory and practicePublication . Petropoulos, Fotios; Apiletti, Daniele; Assimakopoulos, Vassilios; Zied Babai, Mohamed; K. Barrow, Devon; Ben Taieb, Souhaib; Bergmeir, Christoph; J. Bessa, Ricardo; Bijak, Jakub; Boylan, John E.; Browell, Jethro; Carnevale, Claudio; Castle, Jennifer L.; Cirillo, Pasquale; Clements, Michael P.; Cordeiro, Clara; Oliveira, Fernando Luiz; Shari De Baets, Cyrino; Dokumentov, Alexander; Ellison, Joanne; Fiszeder, Piotr; Franses, Philip Hans; Frazier, David T.; Gilliland, Michael; Gönül, M. Sinan; Goodwin, Paul; Grossi, Luigi; Grushka-Cockayne, Yael; Guidolin, Mariangela; Guidolin, Massimo; Gunter, Ulrich; Guo, Xiaojia; Guseo, Renato; Harvey, Nigel; Hendry, David F.; Hollyman, Ross; Januschowski, Tim; eon, Jooyoung J; Richmond R. Jose, Victor; Kang, Yanfei; Koehler, Anne B.; Kolassa, Stephan; Kourentzes, Nikolaos; Leva, Sonia; Li, Feng; Litsiou, Konstantia; Makridakis, Spyros; M. Martin, Gael; Martinez, Andrew B.; Meeran, Sheik; Modis, Theodore; Nikolopoulos, Konstantinos; Önkal, Dilek; Paccagnini, Alessia; Panagiotelis, Anastasios; Panapakidis, Ioannis; Pavía, Jose M.; Pedio, Manuela; Pedregal, Diego J.; Pinson, Pierre; Ramos, Patrícia; Rapach, David E.; Reade, J. James; Rostami-Tabar, Bahman; Rubaszek, Michał; Sermpinis, Georgios; Shang, Han Lin; Spiliotis, Evangelos; Syntetos, Aris A.; Talagala, Priyanga Dilini; Talagala, Thiyanga S.; Tashman, Len; Thomakos, Dimitrios; Thorarinsdottir, Thordis; Todini, Ezio; Trapero Arenas, Juan Ramón; Wang, Xiaoqian; Winkler, Robert L.; Yusupova, Alisa; Ziel, FlorianForecasting has always been at the forefront of decision making and planning. The uncertainty that surrounds the future is both exciting and challenging, with individuals and organisations seeking to minimise risks and maximise utilities. The large number of forecasting applications calls for a diverse set of forecasting methods to tackle real-life challenges. This article provides a non-systematic review of the theory and the practice of forecasting. We provide an overview of a wide range of theoretical, state-of-the-art models, methods, principles, and approaches to prepare, produce, organise, and evaluate forecasts. We then demonstrate how such theoretical concepts are applied in a variety of real-life contexts. We do not claim that this review is an exhaustive list of methods and applications. However, we wish that our encyclopedic presentation will offer a point of reference for the rich work that has been undertaken over the last decades, with some key insights for the future of forecasting theory and practice. Given its encyclopedic nature, the intended mode of reading is non-linear. We offer cross-references to allow the readers to navigate through the various topics. We complement the theoretical concepts and applications covered by large lists of free or open-source software implementations and publicly-available databases.
- A strategy to assess water meter performancePublication . Cordeiro, Clara; Borges, Ana; Ramos, M. RosárioA recurring problem that troubles water companies is that of timely detection of malfunctioning water meters. Indeed, defective water meters impair the management of water supply and diminish water companies’ revenues. The management of nonrevenue water (NRW) is one key issue for improving water use efficiency, reducing gaps between water supply and demand (Ncube and Taigbenu 2019). Water losses in the distribution system can be categorized as either real (leakage) or apparent (commercial) losses (Mutikanga et al. 2011). Water meter under-registration resulted in apparent losses and lost revenue (Moahloli et al. 2019; Fourie et al. 2020), being apparent losses one of the components of NRW. As Criminisi et al. (2009) explain, apparent losses are caused by unauthorized consumption and meter inaccuracies, corresponding not to physical but rather to financial losses. Since they are water volumes taken from the network and consumed but not accounted for, as a consequence, the company will be jeopardized by the unaccounted water volume, resulting in an important impact on the utility’s water and economic balances. A long-known fact is that reducing apparent losses caused by meter inaccuracies can result in substantial short-term increases in utility revenue and lead to increasingly equitable service charges for long-term water consumers (Richards et al. 2010; Kadenge et al. 2020). The accurate measurement of the water collected by meters is crucial in reducing any uncertainty affecting the water balance and has significant technical and economic implications (Pacheco et al. 2020). A cubic meter consumed but not measured reduces the company revenue in quantity equal to the selling price of the last cubic meter of water consumed by that consumer (Arregui et al. 2018). The water companies’ awareness for the responsible use of water has gained importance, with climate changes emphasizing this need. In the context of water scarcity, Oviedo-Ocana et al. ˜(2020) alert to the importance of assessing losses in water distribution systems since the compensation of water losses represents an increase in the source’s water supply. Enhancing that water use efficiency and conservation are priority alternatives to ensure, for example, universal access to drinking water and reducing the number of people suffering from water scarcity. Furthermore, Pacheco et al. (2020) emphasize that water measurement will become an even more critical aspect in the near future because of the increase in the world’s water supplies due to population growth. In this context, one form of water companies to be aware of its important role is to steer the effective water consumption and guarantee an efficient manutention of its equipment, namely the water meters. Current research confirms that several factors affect a water meter’s accuracy, particularly water meterage and total registered volume (Moahloli et al. 2019; Pacheco et al. 2020). Detecting the point in time in which water meters should be replaced implies that they can be substituted proactively to minimize the impact of water consumption nonregistration and under-registration on NRW (Moahloli et al. 2019). There seems to be no specific determination and/or agreement on a water meter lifespan or optimal replacement period. Water meter producers only give a limited warranty against manufacturing defects but do not specify the meters’ lifetime (Moahloli et al. 2019). It is believed that the premature replacement of water meters will result in a higher average life-cycle cost due to the initial fixed costs. However, if a meter is replaced too late, a significant loss of revenue caused by meter nonregistration and under-registration will also increase the average life-cycle cost (Fontanazza et al. 2015). The main studies on this problem have adopted approaches based on laboratory studies, which may implicate two significant issues: (1) the high costs inherent to the laboratory, and (2) the conditions in which the tests are taken upon are far from the real scenario.