Author: "Francesco Pesce" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Francesco Pesce"' showing total 168 results

Start Over Author "Francesco Pesce"

168 results on '"Francesco Pesce"'

1. Safety evaluation of the food enzyme subtilisin from the non‐genetically modified Bacillus paralicheniformis strain AP‐01

Author: EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP), Claude Lambré, José Manuel Barat Baviera, Claudia Bolognesi, Pier Sandro Cocconcelli, Riccardo Crebelli, David Michael Gott, Konrad Grob, Evgenia Lampi, Marcel Mengelers, Alicja Mortensen, Gilles Rivière, Inger‐Lise Steffensen, Christina Tlustos, Henk Van Loveren, Laurence Vernis, Holger Zorn, Yrjö Roos, Jaime Aguilera, Magdalena Andryszkiewicz, Daniele Cavanna, Silvia Peluso, Rita Ferreira deSousa, Francesco Pesce, Yi Liu, and Andrew Chesson
Subjects: Bacillus paralicheniformis, EC 3.4.21.62, EFSA‐Q‐2022‐00601, serine endopeptidase, subtilisin, Nutrition. Foods and food supply, TX341-641, Chemical technology, TP1-1185
Abstract: Abstract The food enzyme subtilisin (EC 3.4.21.62) is produced with the non‐genetically modified Bacillus paralicheniformis strain AP‐01 by Nagase (Europa) GmbH. It was considered free from viable cells of the production organism. The food enzyme is intended to be used in five food manufacturing processes. Since residual amounts of food enzyme‐total organic solids (TOS) are removed in one process, dietary exposure was calculated only for the remaining four food manufacturing processes. It was estimated to be up to 0.875 mg TOS/kg body weight per day in European populations. The production strain of the food enzyme has the capacity to produce bacitracin and thus failed to meet the requirements of the Qualified Presumption of Safety approach. Bacitracin was detected in the industrial fermentation medium but not in the food enzyme itself. However, the limit of detection of the analytical method used for bacitracin was not sufficient to exclude the possible presence of bacitracin at a level representing a risk for the development of antimicrobial resistant bacteria. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and twenty‐eight matches with respiratory allergens, one match with a contact allergen and two matches with food allergens (melon and pomegranate) were found. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme, particularly in individuals sensitised to melon or pomegranate, cannot be excluded, but would not exceed the risk of consuming melon or pomegranate. Based on the data provided, the Panel could not exclude the presence of bacitracin, a medically important antimicrobial, and consequently the safety of this food enzyme could not be established.
Published: 2024
Full Text: View/download PDF

2. Effects of low-sodium bread on dietary compliance and fecal cultivable bacteria in a randomized controlled pilot trial in hypertensive subjects

Author: Carmela Cosola, Francesco Pesce, Maria De Angelis, Valentina Maranzano, Annapaola Zito, Eustacchio Montemurno, Giuseppe Dalfino, Saverio Loiudice, Vincenzo Creanza, Giovanni Pompa, Marco Matteo Ciccone, Giuseppe Grandaliano, Giovanni Stallone, and Loreto Gesualdo
Subjects: Hypertension, Low-salt diet, Low-sodium bread, Blood pressure, Fecal cultivable bacteria, Randomized controlled pilot trial, Nutrition. Foods and food supply, TX341-641, Food processing and manufacture, TP368-456, Medicine (General), R5-920
Abstract: Abstract High salt intake and compliance to low-sodium (LS) diets are critical in hypertension. Salt reduction in processed foods can help to achieve the target sodium intake. To verify the hypothesis that an innovative LS formulation of a traditional bread could result in a reduction of sodium intake and blood pressure, we performed a 6-month randomized controlled pilot trial on hypertensive patients. We additionally explored the effects of sodium restriction on blood pressure and fecal cultivable bacteria. Fifty-seven patients were randomized in three groups. Group A (n = 19) followed a free diet using standard bread (750 mg Na/100 g), group B (n = 18) followed a LS diet (2300 mg Na/die) using standard bread, group C (n = 20) followed a LS diet (2300 mg Na/die) using LS bread (280 mg Na/100 g). We measured 24-h urinary sodium, blood pressure, routine parameters, fecal microbial counts (26 patients). After 6 months, as compared to group A, group C showed a reduction of 24-h urinary sodium excretion (-908 mg/24 h), diastolic pressure (-9 mmHg) and microbial counts of Bacteroides, Porphyromonas, Prevotella , Enterobacteriaceae, Staphylococcus, Micrococcus. These results suggest that LS bread could increase the adherence to a LS diet, reducing sodium excretion, diastolic pressure and abundance of some fecal cultivable bacteria. Trial registration Registration nr. NCT03127553, on 25/04/2017.
Published: 2024
Full Text: View/download PDF

3. Safety evaluation of a food enzyme containing bacillolysin and subtilisin activities from the non‐genetically modified Bacillus amyloliquefaciens strain AR‐383

Author: EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (EFSA CEP Panel), Claude Lambré, José Manuel Barat Baviera, Claudia Bolognesi, Pier Sandro Cocconcelli, Riccardo Crebelli, David Michael Gott, Konrad Grob, Evgenia Lampi, Marcel Mengelers, Alicja Mortensen, Gilles Rivière, Inger‐Lise Steffensen, Christina Tlustos, Henk Van Loveren, Laurence Vernis, Holger Zorn, Yrjö Roos, Magdalena Andryszkiewicz, Daniele Cavanna, Yi Liu, Simone Lunardi, Francesco Pesce, and Andrew Chesson
Subjects: bacillolysin, Bacillus amyloliquefaciens, EC 3.4.21.62, EC 3.4.24.28, food enzyme, subtilisin, Nutrition. Foods and food supply, TX341-641, Chemical technology, TP1-1185
Abstract: Abstract The food enzyme with two declared activities, bacillolysin (EC 3.4.24.28) and subtilisin (EC 3.4.21.62), is produced with the non‐genetically modified Bacillus amyloliquefaciens strain AR‐383 by AB Enzymes GmbH. The food enzyme is intended to be used in nine food manufacturing processes. Since residual amounts of total organic solids (TOS) are removed in the production of distilled alcohol, dietary exposure was calculated only for the remaining eight food manufacturing processes. Exposure was estimated to be up to 1.958 mg TOS/kg body weight per day in European populations. As the production strain qualifies for the qualified presumption of safety approach to safety assessment and no issues of concern arising from the production process of the food enzyme were identified, the Panel considered that no toxicological studies other than the assessment of allergenicity were necessary. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made, and 30 matches were found, including one food allergen (melon). The Panel considered that, under the intended conditions of use, the risk of allergic reactions by dietary exposure to this food enzyme cannot be excluded, but for individuals sensitised to melon, this would not exceed the risk of consuming melon. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
Published: 2024
Full Text: View/download PDF

4. Safety evaluation of the food enzyme bacillolysin from the non‐genetically modified Bacillus amyloliquefaciens strain AE‐NP

Author: EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP), Claude Lambré, José Manuel Barat Baviera, Claudia Bolognesi, Pier Sandro Cocconcelli, Riccardo Crebelli, David Michael Gott, Konrad Grob, Evgenia Lampi, Marcel Mengelers, Alicja Mortensen, Gilles Rivière, Inger‐Lise Steffensen, Christina Tlustos, Henk Van Loveren, Laurence Vernis, Holger Zorn, Yrjö Roos, Magdalena Andryszkiewicz, Daniele Cavanna, Simone Lunardi, Francesco Pesce, and Andrew Chesson
Subjects: bacillolysin, Bacillus amyloliquefaciens, Bacillus metalloendopeptidase, EC 3.4.24.28, food enzyme, Nutrition. Foods and food supply, TX341-641, Chemical technology, TP1-1185
Abstract: Abstract The food enzyme bacillolysin (EC 3.4.24.28) is produced with the non‐genetically modified Bacillus amyloliquefaciens strain AE‐NP by Amano Enzyme Inc. The production strain meets the requirements for the qualified presumption of safety (QPS) approach to safety assessment. The food enzyme is intended to be used in 14 food manufacturing processes. Since residual amounts of total organic solids (TOS) are removed in three manufacturing processes, dietary exposure was calculated only for the remaining 11 food manufacturing processes in which the food enzyme‐TOS is retained. It was estimated to be up to 35.251 mg TOS/kg body weight (bw) per day in European populations. As the production strain qualifies for the QPS approach and no issue of concern arising from the production process of the food enzyme were identified, the Panel considered that no toxicological studies other than the assessment of allergenicity were necessary. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and no match was found. The Panel considered that the risk of allergic reactions by dietary exposure cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
Published: 2024
Full Text: View/download PDF

5. Safety evaluation of the food enzyme bacillolysin from the non‐genetically modified Bacillus amyloliquefaciens strain NZYM‐NB

Author: EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP), Claude Lambré, José Manuel Barat Baviera, Claudia Bolognesi, Pier Sandro Cocconcelli, Riccardo Crebelli, David Michael Gott, Konrad Grob, Evgenia Lampi, Marcel Mengelers, Alicja Mortensen, Gilles Rivière, Inger‐Lise Steffensen, Christina Tlustos, Henk Van Loveren, Laurence Vernis, Holger Zorn, Lieve Herman, Yrjö Roos, Magdalena Andryszkiewicz, Daniele Cavanna, Simone Lunardi, Eleonora Marini, Francesco Pesce, and Andrew Chesson
Subjects: bacillolysin, Bacillus amyloliquefaciens, Bacillus metalloendopeptidase, EC 3.4.24.28, food enzyme, Nutrition. Foods and food supply, TX341-641, Chemical technology, TP1-1185
Abstract: Abstract The food enzyme bacillolysin (EC 3.4.24.28) is produced with the non‐genetically modified Bacillus amyloliquefaciens strain NZYM‐NB by Novozymes A/S. The production strain meets the requirements for qualified presumption of safety (QPS) approach to safety assessment. The food enzyme is intended to be used in eleven food manufacturing processes. Since residual amounts of total organic solids (TOS) are removed during two processes, dietary exposure was estimated only for the remaining nine food manufacturing processes. Exposure was estimated to be up to 1.327 mg TOS/kg body weight per day in European populations. As the production strain qualifies for the QPS approach and no issue of concern arising from the production process of the food enzyme was identified, the Panel considered that no toxicological studies other than the assessment of allergenicity were necessary. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and no match was found. The Panel considered that the risk of allergic reactions by dietary exposure cannot be excluded (except for distilled alcohol production), but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
Published: 2024
Full Text: View/download PDF

6. Safety evaluation of the food enzyme β‐fructofuranosidase from the non‐genetically modified Saccharomyces cerevisiae strain NCYC R693

Author: EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP), Claude Lambré, José Manuel Barat Baviera, Claudia Bolognesi, Pier Sandro Cocconcelli, Riccardo Crebelli, David Michael Gott, Konrad Grob, Evgenia Lampi, Marcel Mengelers, Alicja Mortensen, Gilles Rivière, Inger‐Lise Steffensen, Christina Tlustos, Henk Van Loveren, Laurence Vernis, Holger Zorn, Lieve Herman, Yrjö Roos, Jaime Aguilera, Magdalena Andryszkiewicz, Daniele Cavanna, Yi Liu, Eleonora Marini, Francesco Pesce, Giulio diPiazza, and Andrew Chesson
Subjects: EC 3.2.1.26, food enzyme, invertase, Saccharomyces cerevisiae, β‐d‐fructofuranoside fructohydrolase, β‐fructofuranosidase, Nutrition. Foods and food supply, TX341-641, Chemical technology, TP1-1185
Abstract: Abstract The food enzyme β‐fructofuranosidase (β‐d‐fructofuranoside fructohydrolase; EC 3.2.1.26) is produced with the non‐genetically modified Saccharomyces cerevisiae strain NCYC R693 by Kerry Ingredients & Flavours Ltd. The production strain meets the requirements for the qualified presumption of safety (QPS) approach. The food enzyme is intended to be used in four food manufacturing processes. The dietary exposure to the food enzyme–total organic solids (TOS) was estimated to be up to 2.485 mg TOS/kg body weight per day in European populations. As the production strain qualifies for the QPS approach of safety assessment and no issue of concern arising from the production process of the food enzyme were identified, the Panel considered that no toxicological studies other than the assessment of allergenicity were necessary. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and one match with a tomato allergen was found. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme, particularly in individuals sensitised to tomato, cannot be excluded. However, the likelihood of allergic reactions is expected not to exceed the likelihood of allergic reactions to tomato. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
Published: 2024
Full Text: View/download PDF

7. Safety evaluation of the food enzyme subtilisin from the non‐genetically modified Bacillus licheniformis strain NZYM‐CX

Author: EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP), Claude Lambré, José Manuel Barat Baviera, Claudia Bolognesi, Pier Sandro Cocconcelli, Riccardo Crebelli, David Michael Gott, Konrad Grob, Evgenia Lampi, Marcel Mengelers, Alicja Mortensen, Gilles Rivière, Inger‐Lise Steffensen, Christina Tlustos, Henk Van Loveren, Laurence Vernis, Holger Zorn, Yrjö Roos, Jaime Aguilera, Magdalena Andryszkiewicz, Daniele Cavanna, Silvia Peluso, Giulio diPiazza, Francesco Pesce, Yi Liu, and Andrew Chesson
Subjects: Bacillus licheniformis, EC 3.4.21.62, food enzyme, non‐genetically modified microorganism, subtilisin, Nutrition. Foods and food supply, TX341-641, Chemical technology, TP1-1185
Abstract: Abstract The food enzyme subtilisin (EC 3.4.21.62) is produced with the non‐genetically modified Bacillus licheniformis strain NZYM‐CX by Novozymes A/S. The production strain met the requirements for the qualified presumption of safety (QPS) approach. The food enzyme is intended to be used in eight food manufacturing processes: processing of cereals and other grains for the production of brewed products; processing of dairy products for the production of modified milk proteins and flavouring preparations; processing of plant‐ and fungal‐derived products for the production of plant‐based analogues of milk and milk products, protein hydrolysates and edible oils from algae; processing of meat and fish products for the production of protein hydrolysates; processing of yeast and yeast products. Since residual amounts of total organic solids (TOS) are removed in the production of edible oils from algae, dietary exposure was calculated only for the remaining seven food manufacturing processes. Exposure was estimated to be up to 2.393 mg TOS/kg body weight (bw) per day in European populations. As the production strain qualified for the QPS approach and no issues of concern arose from the production process of the food enzyme, the Panel considered that toxicological studies were unnecessary. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was performed, and a total of 20 matches were found, 17 to respiratory allergens, two to food allergens (found in muskmelon and pomegranate) and one to a contact allergen. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme cannot be excluded, especially in individuals sensitised to muskmelon or pomegranate, but would not exceed the risk of consuming these foods. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
Published: 2023
Full Text: View/download PDF

8. Safety evaluation of a food enzyme containing endo‐polygalacturonase and pectin lyase activities from the non‐genetically modified Aspergillus tubingensis strain NZYM‐PE

Author: EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP), Claude Lambré, José Manuel Barat Baviera, Claudia Bolognesi, Pier Sandro Cocconcelli, Riccardo Crebelli, David Michael Gott, Konrad Grob, Evgenia Lampi, Marcel Mengelers, Alicja Mortensen, Gilles Rivière, Inger‐Lise Steffensen, Christina Tlustos, Henk Van Loveren, Laurence Vernis, Holger Zorn, Yrjö Roos, Magdalena Andryszkiewicz, Ana Criado, Yi Liu, Simone Lunardi, Francesco Pesce, and Andrew Chesson
Subjects: food enzyme, endo‐polygalacturonase, (1–4)‐α‐D‐galacturonan glycanohydrolase, EC 3.2.1.15, pectin lyase, (1–4)‐6‐O‐methyl‐α‐D‐galacturonan lyase, Nutrition. Foods and food supply, TX341-641, Chemical technology, TP1-1185
Abstract: Abstract The food enzyme with the declared activities endo‐polygalacturonase ((1–4)‐α‐D‐galacturonan glycanohydrolase; EC 3.2.1.15) and pectin lyase ((1–4)‐6‐O‐methyl‐α‐D‐galacturonan lyase; EC 4.2.2.10) is produced with the non‐genetically modified Aspergillus tubingensis strain NZYM‐PE by Novozymes A/S. It is intended to be used in four food manufacturing processes: fruit and vegetable processing for juice production, fruit and vegetable processing for products other than juices, refined olive oil production and wine and wine vinegar production. Since residual amounts of total organic solids (TOS) are removed during production, dietary exposure was not calculated for refined olive oil production. For the remaining three food processes, it was estimated to be up to 0.132 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90‐day oral toxicity study in rats. The Panel identified a no observed adverse effect level (NOAEL) of 1,430 mg TOS/kg bw per day, the highest dose tested, which when compared with the estimated dietary exposure, resulted in a margin of exposure above 10,833. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and 13 matches were found, including one food allergen (papaya). The Panel considered that, under the intended conditions of use, the risk of allergic reactions upon dietary exposure to this food enzyme cannot be excluded, in particular for individuals sensitised to papaya, but that the risk will not exceed that of consumption of papaya. In addition, oral allergy reactions cannot be excluded in pollen‐sensitised individuals. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.
Published: 2023
Full Text: View/download PDF

9. Food manufacturing processes and technical data used in the exposure assessment of food enzymes

Author: EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP), Claude Lambré, José Manuel Barat Baviera, Claudia Bolognesi, Pier Sandro Cocconcelli, Riccardo Crebelli, David Michael Gott, Konrad Grob, Evgenia Lampi, Marcel Mengelers, Alicja Mortensen, Gilles Rivière, Inger‐Lise Steffensen, Christina Tlustos, Henk vanLoveren, Laurence Vernis, Holger Zorn, Yrjö Roos, Kyriaki Apergi, Daniele Cavanna, Yi Liu, Francesco Pesce, Giulio diPiazza, Rita Ferreira deSousa, and Andrew Chesson
Subjects: enzyme, food manufacturing process, conversion factor, dietary exposure, calculator, FEIM, Nutrition. Foods and food supply, TX341-641, Chemical technology, TP1-1185
Abstract: Abstract Food enzymes are used for technical purposes in the production of food ingredients or foods‐as‐consumed. In the European Union, the safety of a food enzyme is evaluated by EFSA on the basis of a technical dossier provided by an applicant. Dietary exposure is an integral part of the risk assessment of food enzymes. To develop exposure models specific to each food manufacturing process in which food enzymes are used, different input data are required which are then used in tandem with technical conversion factors. This allows the use levels of food enzyme to be related to food consumption data collected in dietary surveys. For each food manufacturing process, EFSA identified a list of food groups (FoodEx1 classification system) and collated technical conversion factors. To ensure a correct and uniform application of these input data in the assessment of food enzyme dossiers, stakeholders were consulted via open calls‐for‐data. In addition to publishing and updating the identified input parameters on an annual basis, single‐process‐specific calculators of the Food Enzyme Intake Models (FEIMs) have been developed. These calculators have been deposited at https://zenodo.org/ since 2018 for open access. By 2023, EFSA had compiled the input data for a total of 40 food manufacturing processes in which food enzymes are employed. In this document, the food manufacturing processes are structured, food groups classified initially in the FoodEx1 system are translated into the FoodEx2 system, and technical factors are adjusted to reflect the more detailed and standardised FoodEx2 nomenclature. The development of an integrated FEIM‐web tool using this collection of input data is released in 2024. This webtool is able to estimate the exposure to the food enzyme–total organic solids (TOS) when employed in single or multiple food manufacturing processes.
Published: 2023
Full Text: View/download PDF

10. Corrigendum: Can vitamin D status influence seroconversion to SARS-COV2 vaccines?

Author: Endrit Shahini, Francesco Pesce, Antonella Argentiero, and Antonio Giovanni Solimando
Subjects: COVID-19, coronavirus, vitamin D, antibodies, serology, autoimmune disorders, Immunologic diseases. Allergy, RC581-607
Published: 2023
Full Text: View/download PDF

11. Can vitamin D status influence seroconversion to SARS-COV2 vaccines?

Author: Endrit Shahini, Francesco Pesce, Antonella Argentiero, and Antonio Giovanni Solimando
Subjects: COVID-19, coronavirus, vitamin D, antibodies, serology, autoimmune disorders, Immunologic diseases. Allergy, RC581-607
Abstract: Existing data indicate an association between vitamin D deficiency and increased severity of respiratory distress due to COVID-19 infection, especially in high-risk populations. To date, the effect of vitamin D on immunogenicity to SARS-CoV-2 vaccines has been investigated solely in young healthcare workers in a few studies, yielding conflicting findings, yet highlighting that the response to immunization is inversely related to age. Vitamin D status can potentially influence the antibody titers in people with a previous (or naïve) SARS-CoV-2 infection and vaccination, given its role in immune regulatory functions. From this standpoint, vitamin D supplementation can help reduce the risk of SARS-CoV-2 infection, COVID-19 severity/mortality and rebalance immunological function, particularly in subjects with vigorous T lymphocyte responses to COVID-19. However, more research is needed to establish a correlation between vitamin D status and the generation of protective serological responses to SARS-CoV-2 vaccination.
Published: 2022
Full Text: View/download PDF

12. A neural network for glomerulus classification based on histological images of kidney biopsy

Author: Giacomo Donato Cascarano, Francesco Saverio Debitonto, Ruggero Lemma, Antonio Brunetti, Domenico Buongiorno, Irio De Feudis, Andrea Guerriero, Umberto Venere, Silvia Matino, Maria Teresa Rocchetti, Michele Rossini, Francesco Pesce, Loreto Gesualdo, and Vitoantonio Bevilacqua
Subjects: CKD, Kidney, Glomerulus classification, Morphological features, Texture features, ANN, Computer applications to medicine. Medical informatics, R858-859.7
Abstract: Abstract Background Computer-aided diagnosis (CAD) systems based on medical images could support physicians in the decision-making process. During the last decades, researchers have proposed CAD systems in several medical domains achieving promising results. CAD systems play an important role in digital pathology supporting pathologists in analyzing biopsy slides by means of standardized and objective workflows. In the proposed work, we designed and tested a novel CAD system module based on image processing techniques and machine learning, whose objective was to classify the condition affecting renal corpuscles (glomeruli) between sclerotic and non-sclerotic. Such discrimination is useful for the biopsy slides evaluation performed by pathologists. Results We collected 26 digital slides taken from the kidneys of 19 donors with Periodic Acid-Schiff staining. Expert pathologists have conducted the slides preparation, digital acquisition and glomeruli annotations. Before setting the classifiers, we evaluated several feature extraction techniques from the annotated regions. Then, a feature reduction procedure followed by a shallow artificial neural network allowed discriminating between the glomeruli classes. We evaluated the workflow considering an independent dataset (i.e., processing images not used in the training procedure). Ten independent runs of the training algorithm, and evaluation, allowed achieving MCC and Accuracy of 0.95 (± 0.01) and 0.99 (standard deviation
Published: 2021
Full Text: View/download PDF

13. Case report: Novel FHR2 variants in atypical Hemolytic Uremic Syndrome: A case study of a translational medicine approach in renal transplantation

Author: Emma Diletta Stea, Christine Skerka, Matteo Accetturo, Francesco Pesce, Thorsten Wiech, Andrea Hartman, Paola Pontrelli, Francesca Conserva, Giuseppe Castellano, Peter F. Zipfel, and Loreto Gesualdo
Subjects: complement associated kidney diseases, complement inhibition, Factor H related proteins, thrombotic microangiopathy, aHUS, Immunologic diseases. Allergy, RC581-607
Abstract: Atypical hemolytic–uremic syndrome (aHUS) is a severe thrombotic microangiopathy in which kidney involvement is common. aHUS can be due to either genetic or acquired abnormalities, with most abnormalities affecting the alternative complement pathway. Several genetic factors/alterations can drive the clinical presentation, therapeutic response, and risk of recurrence, especially recurrence following kidney transplantation. We report here the case of a 22-year-old man who developed a severe form of aHUS. Renal biopsy revealed thrombotic microangiopathy and features of chronic renal damage. Despite two eculizumab infusions, the patient remained dialysis dependent. Two novel rare variants, c.109G>A (p.E37K) and c.159 C>A (p.Y53*), were identified in the factor H-related 2 (FHR2) gene, and western blot analysis revealed a significant reduction in the level of FHR2 protein in the patient’s serum. Although FHR2 involvement in complement 3 glomerulopathy has been reported previously, a role for FRH2 as a complement modulator has not yet been definitively shown. In addition, no cases of aHUS in individuals with FHR2 variants have been reported. Given the role of FHRs in the complement system and the fact that this patient was a candidate for a kidney transplant, we studied the relevance of low FHR2 plasma levels through a set of functional in vitro assays. The aim of our work was to determine if low FHR2 plasma levels could influence complement control at the endothelial surface with a view to identifying a therapeutic approach tailored to this specific patient. Interestingly, we observed that low FHR2 levels in the patient’s serum could induce complement activation, as well as C5b–9 deposition on human endothelial cells, and affected cell morphology. As C5b–9 deposition is a prerequisite for endothelial cell damage, these results suggest that extremely low FHR2 plasma levels increase the risk of aHUS. Given their ability to reduce C5b–9 deposition, recombinant FHR2 and eculizumab were tested in vitro and found to inhibit hemolysis and endothelial cell surface damage. Both molecules showed effective and comparable profiles. Based on these results, the patient underwent a kidney transplant, and received eculizumab as induction and maintenance therapy. Five years after transplantation, the patient remains in good general health, with stable graft function and no evidence of disease recurrence. To our knowledge, this is first reported case of an aHUS patient carrying FHR2 mutations and provides an example of a translational therapeutic approach in kidney transplantation.
Published: 2022
Full Text: View/download PDF

14. Pre-Transplant Expression of CCR-2 in Kidney Transplant Recipients Is Associated With the Development of Delayed Graft Function

Author: Paola Pontrelli, Simona Simone, Federica Rascio, Francesco Pesce, Francesca Conserva, Barbara Infante, Giuseppe Castellano, Fabio Sallustio, Marco Fiorentino, Gianluigi Zaza, Anna Gallone, Michele Battaglia, Pasquale Ditonno, Giovanni Stallone, Loreto Gesualdo, and Giuseppe Grandaliano
Subjects: kidney transplantation, delayed graft function, gene expression, peripheral blood mononuclear cells, CCR-2, Immunologic diseases. Allergy, RC581-607
Abstract: BackgroundDelayed graft function (DGF) leads to a reduced graft survival. Donors’ features have been always considered as key pathogenic factors in this setting. The aim of our study was to evaluate the recipients’ characteristics in the development of DGF.MethodsWe enrolled 932 kidney graft recipients from 466 donors; 226 recipients experienced DGF. In 290 donors, both recipients presented with early graft function (EGF, group A), in 50 both recipients experienced DGF (group B), and in 126 one recipient presented with DGF and the other with EGF (group C). In group C, we selected 7 couples of DGF/EGF recipients and we evaluated the transcriptomic profile by microarray on circulating mononuclear cells harvested before transplantation. Results were validated by qPCR in an independent group of 25 EGF/DGF couples.FindingsIn the whole study group, DGF was associated with clinical characteristics related to both donors and recipient. In group C, DGF was significantly associated with body mass index, hemodialysis, and number of mismatches. In the same group, we identified 411 genes differently expressed before transplantation between recipients discordant for the transplant outcome. Those genes were involved in immune dysfunction and inflammation. In particular, we observed a significant increase in DGF patients in the expression of C–C chemokine receptor type 2 (CCR2), the monocyte chemoattractant protein-1 (MCP-1) receptor. CCR-2 upregulation was confirmed in an independent cohort of patients.ConclusionsOur results suggest that recipients’ clinical/immunological features, potentially modulated by dialysis, are associated with the development of DGF independently of donors’ features.
Published: 2022
Full Text: View/download PDF

15. A comparison between two semantic deep learning frameworks for the autosomal dominant polycystic kidney disease segmentation based on magnetic resonance images

Author: Vitoantonio Bevilacqua, Antonio Brunetti, Giacomo Donato Cascarano, Andrea Guerriero, Francesco Pesce, Marco Moschetta, and Loreto Gesualdo
Subjects: Deep learning, Convolutional neural network, Semantic segmentation, R-CNN, ADPKD, Magnetic resonance, Computer applications to medicine. Medical informatics, R858-859.7
Abstract: Abstract Background The automatic segmentation of kidneys in medical images is not a trivial task when the subjects undergoing the medical examination are affected by Autosomal Dominant Polycystic Kidney Disease (ADPKD). Several works dealing with the segmentation of Computed Tomography images from pathological subjects were proposed, showing high invasiveness of the examination or requiring interaction by the user for performing the segmentation of the images. In this work, we propose a fully-automated approach for the segmentation of Magnetic Resonance images, both reducing the invasiveness of the acquisition device and not requiring any interaction by the users for the segmentation of the images. Methods Two different approaches are proposed based on Deep Learning architectures using Convolutional Neural Networks (CNN) for the semantic segmentation of images, without needing to extract any hand-crafted features. In details, the first approach performs the automatic segmentation of images without any procedure for pre-processing the input. Conversely, the second approach performs a two-steps classification strategy: a first CNN automatically detects Regions Of Interest (ROIs); a subsequent classifier performs the semantic segmentation on the ROIs previously extracted. Results Results show that even though the detection of ROIs shows an overall high number of false positives, the subsequent semantic segmentation on the extracted ROIs allows achieving high performance in terms of mean Accuracy. However, the segmentation of the entire images input to the network remains the most accurate and reliable approach showing better performance than the previous approach. Conclusion The obtained results show that both the investigated approaches are reliable for the semantic segmentation of polycystic kidneys since both the strategies reach an Accuracy higher than 85%. Also, both the investigated methodologies show performances comparable and consistent with other approaches found in literature working on images from different sources, reducing both the invasiveness of the analyses and the interaction needed by the users for performing the segmentation task.
Published: 2019
Full Text: View/download PDF

16. Deciphering the Alphabet of Disorder—Glu and Asp Act Differently on Local but Not Global Properties

Author: Mette Ahrensback Roesgaard, Jeppe E. Lundsgaard, Estella A. Newcombe, Nina L. Jacobsen, Francesco Pesce, Emil E. Tranchant, Søren Lindemose, Andreas Prestel, Rasmus Hartmann-Petersen, Kresten Lindorff-Larsen, and Birthe B. Kragelund
Subjects: Dss1, intrinsically disordered protein, IDPs, molecular dynamics, NMR, sequence composition, Microbiology, QR1-502
Abstract: Compared to folded proteins, the sequences of intrinsically disordered proteins (IDPs) are enriched in polar and charged amino acids. Glutamate is one of the most enriched amino acids in IDPs, while the chemically similar amino acid aspartate is less enriched. So far, the underlying functional differences between glutamates and aspartates in IDPs remain poorly understood. In this study, we examine the differential effects of aspartate and glutamates in IDPs by comparing the function and conformational ensemble of glutamate and aspartate variants of the disordered protein Dss1, using a range of assays, including interaction studies, nuclear magnetic resonance spectroscopy, small-angle X-ray scattering and molecular dynamics simulation. First, we analyze the sequences of the rapidly growing database of experimentally verified IDPs (DisProt) and show that glutamate enrichment is not caused by a taxonomy bias in IDPs. From analyses of local and global structural properties as well as cell growth and protein-protein interactions using a model acidic IDP from yeast and three Glu/Asp variants, we find that while the Glu/Asp variants support similar function and global dimensions, the variants differ in their binding affinities and population of local transient structural elements. We speculate that these local structural differences may play roles in functional diversity, where glutamates can support increased helicity, important for folding and binding, while aspartates support extended structures and form helical caps, as well as playing more relevant roles in, e.g., transactivation domains and ion-binding.
Published: 2022
Full Text: View/download PDF

17. WWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling

Author: Huimei Chen, Aida Moreno-Moral, Francesco Pesce, Nithya Devapragash, Massimiliano Mancini, Ee Ling Heng, Maxime Rotival, Prashant K. Srivastava, Nathan Harmston, Kirill Shkura, Owen J. L. Rackham, Wei-Ping Yu, Xi-Ming Sun, Nicole Gui Zhen Tee, Elisabeth Li Sa Tan, Paul J. R. Barton, Leanne E. Felkin, Enrique Lara-Pezzi, Gianni Angelini, Cristina Beltrami, Michal Pravenec, Sebastian Schafer, Leonardo Bottolo, Norbert Hubner, Costanza Emanueli, Stuart A. Cook, and Enrico Petretto
Subjects: Science
Abstract: Pathological cardiac fibrosis is a hallmark of diseases leading to heart failure. Here, the authors used systems genetics to identify a pro-fibrotic gene network regulated by WWP2, a E3 ubiquitin ligase, which orchestrates the nucleocytoplasmic shuttling and transcriptional activity of SMAD2 in the diseased heart.
Published: 2019
Full Text: View/download PDF

18. Network Proximity-Based Drug Repurposing Strategy for Early and Late Stages of Primary Biliary Cholangitis

Author: Endrit Shahini, Giuseppe Pasculli, Andrea Mastropietro, Paola Stolfi, Paolo Tieri, Davide Vergni, Raffaele Cozzolongo, Francesco Pesce, and Gianluigi Giannelli
Subjects: autoimmune liver disease, cholestatic diseases, primary biliary cirrhosis, primary sclerosing cholangitis, drug repurposing, network medicine, Biology (General), QH301-705.5
Abstract: Primary biliary cholangitis (PBC) is a chronic, cholestatic, immune-mediated, and progressive liver disorder. Treatment to preventing the disease from advancing into later and irreversible stages is still an unmet clinical need. Accordingly, we set up a drug repurposing framework to find potential therapeutic agents targeting relevant pathways derived from an expanded pool of genes involved in different stages of PBC. Starting with updated human protein–protein interaction data and genes specifically involved in the early and late stages of PBC, a network medicine approach was used to provide a PBC “proximity” or “involvement” gene ranking using network diffusion algorithms and machine learning models. The top genes in the proximity ranking, when combined with the original PBC-related genes, resulted in a final dataset of the genes most involved in PBC disease. Finally, a drug repurposing strategy was implemented by mining and utilizing dedicated drug–gene interaction and druggable genome information knowledge bases (e.g., the DrugBank repository). We identified several potential drug candidates interacting with PBC pathways after performing an over-representation analysis on our initial 1121-seed gene list and the resulting disease-associated (algorithm-obtained) genes. The mechanism and potential therapeutic applications of such drugs were then thoroughly discussed, with a particular emphasis on different stages of PBC disease. We found that interleukin/EGFR/TNF-alpha inhibitors, branched-chain amino acids, geldanamycin, tauroursodeoxycholic acid, genistein, antioestrogens, curcumin, antineovascularisation agents, enzyme/protease inhibitors, and antirheumatic agents are promising drugs targeting distinct stages of PBC. We developed robust and transparent selection mechanisms for prioritizing already approved medicinal products or investigational products for repurposing based on recognized unmet medical needs in PBC, as well as solid preliminary data to achieve this goal.
Published: 2022
Full Text: View/download PDF

19. Glomerulonephritis in AKI: From Pathogenesis to Therapeutic Intervention

Author: Francesco Pesce, Emma D. Stea, Michele Rossini, Marco Fiorentino, Fausta Piancone, Barbara Infante, Giovanni Stallone, Giuseppe Castellano, and Loreto Gesualdo
Subjects: AKI, glomerulonephritis, antibodies, complement, immunosuppression, Medicine (General), R5-920
Abstract: Acute kidney injury (AKI) is increasingly emerging as a global emergency. Sepsis, major surgery, and nephrotoxic drugs are the main causes of AKI in hospitalized patients. However, glomerulonephritis accounts for about 10% of AKI episodes in adults, mainly related to rapidly progressive glomerulonephritis resulting from granulomatous polyangiitis (GPA, Wegener granulomatosis), microscopic polyangiitis (MPA), and anti-glomerular basement membrane (GBM) disease. Also, diffuse proliferative lupus nephritis, immunoglobulin A nephropathy, post-streptococcal glomerulonephritis, mixed cryoglobulinemia, mesangiocapillary glomerulonephritis, membranous nephropathy, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and scleroderma can induce acute renal failure. Early diagnosis of AKI due to glomerulonephritis is crucial for prompt, effective management to improve short- and long-term outcomes. Kidney biopsy is the gold standard for the diagnosis of glomerular disease, but it is not frequently performed in critically ill patients because of their clinical conditions. In this setting, a growing number of diagnostic assays can support the working hypothesis, including antineutrophil cytoplasmic antibodies (ANCAs), anti-double-stranded DNA antibodies, anti-GBM antibodies, antistreptolysin O and anti-DNase B antibodies, cryoglobulins, antiphospholipid antibodies, and complement levels. Therapeutic strategies in AKI patients with glomerulonephritis include high-dose corticosteroids, cyclophosphamide, and plasma exchange. This article reviews the wide spectrum of glomerulopathies associated with AKI, describing the immunological mechanisms underlying glomerular diseases and presenting an overview of the therapeutic options.
Published: 2021
Full Text: View/download PDF

20. Predictive Machine Learning Models and Survival Analysis for COVID-19 Prognosis Based on Hematochemical Parameters

Author: Nicola Altini, Antonio Brunetti, Stefano Mazzoleni, Fabrizio Moncelli, Ilenia Zagaria, Berardino Prencipe, Erika Lorusso, Enrico Buonamico, Giovanna Elisiana Carpagnano, Davide Fiore Bavaro, Mariacristina Poliseno, Annalisa Saracino, Annalisa Schirinzi, Riccardo Laterza, Francesca Di Serio, Alessia D’Introno, Francesco Pesce, and Vitoantonio Bevilacqua
Subjects: COVID-19, machine learning, Kaplan–Meier, Cox regression, hematochemical parameters, prognostic markers, Chemical technology, TP1-1185
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of millions of individuals and caused millions of deaths worldwide. Predicting the clinical course of the disease is of pivotal importance to manage patients. Several studies have found hematochemical alterations in COVID-19 patients, such as inflammatory markers. We retrospectively analyzed the anamnestic data and laboratory parameters of 303 patients diagnosed with COVID-19 who were admitted to the Polyclinic Hospital of Bari during the first phase of the COVID-19 global pandemic. After the pre-processing phase, we performed a survival analysis with Kaplan–Meier curves and Cox Regression, with the aim to discover the most unfavorable predictors. The target outcomes were mortality or admission to the intensive care unit (ICU). Different machine learning models were also compared to realize a robust classifier relying on a low number of strongly significant factors to estimate the risk of death or admission to ICU. From the survival analysis, it emerged that the most significant laboratory parameters for both outcomes was C-reactive protein min; HR=17.963 (95% CI 6.548–49.277, p < 0.001) for death, HR=1.789 (95% CI 1.000–3.200, p = 0.050) for admission to ICU. The second most important parameter was Erythrocytes max; HR=1.765 (95% CI 1.141–2.729, p < 0.05) for death, HR=1.481 (95% CI 0.895–2.452, p = 0.127) for admission to ICU. The best model for predicting the risk of death was the decision tree, which resulted in ROC-AUC of 89.66%, whereas the best model for predicting the admission to ICU was support vector machine, which had ROC-AUC of 95.07%. The hematochemical predictors identified in this study can be utilized as a strong prognostic signature to characterize the severity of the disease in COVID-19 patients.
Published: 2021
Full Text: View/download PDF

21. Performing an Ultrasound-Guided Percutaneous Needle Kidney Biopsy: An Up-To-Date Procedural Review

Author: Antonio Granata, Giulio Distefano, Francesco Pesce, Yuri Battaglia, Paola Suavo Bulzis, Massimo Venturini, Stefano Palmucci, Vito Cantisani, Antonio Basile, and Loreto Gesualdo
Subjects: kidney, ultrasound, biopsy, chronic kidney disease, acute kidney disease, proteinuria, Medicine (General), R5-920
Abstract: Ultrasound-guided percutaneous renal biopsy (PRB) has revolutionized the clinical practice of nephrology in the last decades. PRB remains an essential tool for the diagnosis, prognosis, and therapeutic management of several renal diseases and for the assessment of renal involvement in systemic diseases. In this study, we examine the different applications and provide a review of the current evidence on the periprocedural management of patients. PRB is recommended in patients with significant proteinuria, hematuria, acute kidney injury, unexpected worsening of renal function, and allograft dysfunction after excluding pre- and post-renal causes. A preliminary ultrasound examination is needed to assess the presence of anatomic anomalies of the kidney and to identify vessels that might be damaged by the needle during the procedure. Kidney biopsy is usually performed in the prone position on the lower pole of the left kidney, whereas in patients with obesity, the supine antero-lateral position is preferred. After preparing a sterile field and the injection of local anesthetics, an automatic spring-loaded biopsy gun is used under ultrasound guidance to obtain samples of renal parenchyma for histopathology. After the procedure, an ultrasound scan must be performed for the prompt identification of potential early bleeding complications. As 33% of complications occur after 8 h and 91% occur within 24 h, the ideal post-procedural observation time is 24 h. PRB is a safe procedure and should be considered a routine part of the clinical practice of nephrology.
Published: 2021
Full Text: View/download PDF

22. Safety and Efficacy of Eculizumab Therapy in Multiple Sclerosis: A Case Series

Author: Marco Allinovi, Angelo Bellinvia, Francesco Pesce, Sabrina Milan Manani, Lorenzo Razzolini, Brigida Brezzi, Paolo Protopapa, Vittorio Mantero, Leonardo Caroti, Calogero Lino Cirami, Maria Pia Amato, and Lucia Del Vecchio
Subjects: multiple sclerosis, complement, eculizumab, interferon beta, disease-modifying therapy, adverse event, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: (1) Background: Complement system activation has been proposed as one of the different factors that contribute to Multiple Sclerosis (MS) pathogenesis. In this study, we aimed to describe the potential effects of eculizumab, an anticomplement therapy, on MS disease activity in a cohort of relapsing–remitting (RR) MS patients who discontinued IFN-β therapy due to IFN-β-related thrombotic microangiopathy (TMA) onset. (2) Methods: In this retrospective observational multicentric study, we searched for all patients with MS treated by eculizumab with a survey of several nephrological and neurological centers (over 45 centers). (3) Results: Nine patients were included. The mean follow-up time under eculizumab was 3.72 ± 2.58 years. There were no significant differences in disease activity (EDSS, relapses, new T2, and/or Gd-enhancing lesions at MRI) considering the two years before and after eculizumab therapy. No adverse events potentially related to eculizumab therapy were reported during follow-up. (4) Conclusions: In this preliminary study, we described a good safety profile for eculizumab therapy in MS. However, the available data are not sufficient to make firm conclusions about the possible efficacy of eculizumab as a disease-modifying therapy for MS patients.
Published: 2021
Full Text: View/download PDF

23. Role of Contrast-Enhanced Ultrasound (CEUS) in Native Kidney Pathology: Limits and Fields of Action

Author: Antonio Granata, Irene Campo, Paolo Lentini, Francesco Pesce, Loreto Gesualdo, Antonio Basile, Vito Cantisani, Matthias Zeiler, and Michele Bertolotto
Subjects: contrast-enhanced ultrasound, chronic kidney disease, ultrasonography, CEUS, renal disease, nephropathies, Medicine (General), R5-920
Abstract: Gray scale ultrasound has an important diagnostic role in native kidney disease. Low cost, absence of ionizing radiation and nephrotoxicity, short performance time, and repeatability even at the bedside, are the major advantages of this technique. The introduction of contrast enhancement ultrasound (CEUS) in daily clinical practice has significantly reduced the use of contrast enhancement computed tomography (CECT) and contrast enhancement magnetic resonance (CEMR), especially in patients with renal disease. Although there are many situations in which CECT and CEMRI are primarily indicated, their use may be limited by the administration of the contrast medium, which may involve a risk of renal function impairment, especially in the elderly, and in patients with acute kidney injury (AKI) and moderate to severe chronic kidney disease (CKD). In these cases, CEUS can be a valid diagnostic choice. To date, numerous publications have highlighted the role of CEUS in the study of parenchymal micro-vascularization and renal pathology by full integration with second level imaging methods (CECT and CEMRI) both in patients with normal renal function and with diseased kidneys. The aim of this review is to offer an updated overview of the limitations and potential applications of CEUS in native kidney disease.
Published: 2021
Full Text: View/download PDF

24. Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy

Author: Matthias Heinig, Michiel E. Adriaens, Sebastian Schafer, Hanneke W. M. van Deutekom, Elisabeth M. Lodder, James S. Ware, Valentin Schneider, Leanne E. Felkin, Esther E. Creemers, Benjamin Meder, Hugo A. Katus, Frank Rühle, Monika Stoll, François Cambien, Eric Villard, Philippe Charron, Andras Varro, Nanette H. Bishopric, Alfred L. George, Cristobal dos Remedios, Aida Moreno-Moral, Francesco Pesce, Anja Bauerfeind, Franz Rüschendorf, Carola Rintisch, Enrico Petretto, Paul J. Barton, Stuart A. Cook, Yigal M. Pinto, Connie R. Bezzina, and Norbert Hubner
Subjects: Genetics, Gene expression, eQTL, Dilated cardiomyopathy, Heart, Biology (General), QH301-705.5, QH426-470
Abstract: Abstract Background Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits, including cardiovascular diseases. Results Here we report the first in-depth survey of heart transcriptome variation using RNA-sequencing in 97 patients with dilated cardiomyopathy and 108 non-diseased controls. We reveal extensive differences of gene expression and splicing between dilated cardiomyopathy patients and controls, affecting known as well as novel dilated cardiomyopathy genes. Moreover, we show a widespread effect of genetic variation on the regulation of transcription, isoform usage, and allele-specific expression. Systematic annotation of genome-wide association SNPs identifies 60 functional candidate genes for heart phenotypes, representing 20% of all published heart genome-wide association loci. Focusing on the dilated cardiomyopathy phenotype we found that eQTL variants are also enriched for dilated cardiomyopathy genome-wide association signals in two independent cohorts. Conclusions RNA transcription, splicing, and allele-specific expression are each important determinants of the dilated cardiomyopathy phenotype and are controlled by genetic factors. Our results represent a powerful resource for the field of cardiovascular genetics.
Published: 2017
Full Text: View/download PDF

25. Wars2 is a determinant of angiogenesis

Author: Mao Wang, Patrick Sips, Ester Khin, Maxime Rotival, Ximing Sun, Rizwan Ahmed, Anissa Anindya Widjaja, Sebastian Schafer, Permeen Yusoff, Pervinder Kaur Choksi, Nicole Shi Jie Ko, Manvendra K. Singh, David Epstein, Yuguang Guan, Josef Houštěk, Tomas Mracek, Hana Nuskova, Brittney Mikell, Jessie Tan, Francesco Pesce, Frantisek Kolar, Leonardo Bottolo, Massimiliano Mancini, Norbert Hubner, Michal Pravenec, Enrico Petretto, Calum MacRae, and Stuart A Cook
Subjects: Science
Abstract: Blood supply to the heart is crucial for cardiac function. Here, the authors show that the mitochondrial tryptophanyl-tRNA synthetase, WARS2, drives blood vessel generation in zebrafish and rats and that inhibition of Wars2 diminishes blood vessel growth both within and outside in the heart, suggesting a new target for manipulating angiogenesis.
Published: 2016
Full Text: View/download PDF

26. Author Correction: WWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling

Author: Huimei Chen, Aida Moreno-Moral, Francesco Pesce, Nithya Devapragash, Massimiliano Mancini, Ee Ling Heng, Maxime Rotival, Prashant K. Srivastava, Nathan Harmston, Kirill Shkura, Owen J. L. Rackham, Wei-Ping Yu, Xi-Ming Sun, Nicole Gui Zhen Tee, Elisabeth Li Sa Tan, Paul J. R. Barton, Leanne E. Felkin, Enrique Lara-Pezzi, Gianni Angelini, Cristina Beltrami, Michal Pravenec, Sebastian Schafer, Leonardo Bottolo, Norbert Hubner, Costanza Emanueli, Stuart A. Cook, and Enrico Petretto
Subjects: Science
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019
Full Text: View/download PDF

27. PSyGS Gen A Generator of Domain-Specific Architectures to Accelerate Sparse Linear System Resolution.

Author: Niccolo Nicolosi, Francesco Renato Negri, Francesco Pesce, Francesco Peverelli, Davide Conficconi, and Marco Domenico Santambrogio
Published: 2024
Full Text: View/download PDF

28. Amare per credere: La fede cristiana alla prova delle relazioni

Author: Francesco Pesce
Published: 2023

29. Correlation Between Platelet Function Analyzer-100 Testing and Bleeding Events After Percutaneous Kidney Biopsy

Author: Prof. Carlo Manno, Dott. Francesco Pesce, Dott. Michele Rossini, Dott. Vincenzo Di Leo, and Loreto GESUALDO, Full Professor of Nephrology
Published: 2019

30. Alta fedeltà: Il matrimonio cristiano e la coppia felice e generativa

Author: Francesco Pesce
Published: 2022

31. An Innovative Neural Network Framework for Glomerulus Classification Based on Morphological and Texture Features Evaluated in Histological Images of Kidney Biopsy.

Author: Giacomo Donato Cascarano, Francesco Saverio Debitonto, Ruggero Lemma, Antonio Brunetti, Domenico Buongiorno, Irio De Feudis, Andrea Guerriero, Michele Rossini, Francesco Pesce, Loreto Gesualdo, and Vitoantonio Bevilacqua
Published: 2019
Full Text: View/download PDF

32. Strategies to Reduce Acrylamide Formation During Food Processing Focusing on Cereals, Children and Toddler Consumption: A Review

Author: Francesco Pesce, Valentina Ponzo, Davide Mazzitelli, Paolo Varetto, Simona Bo, and I. Sam Saguy
Subjects: General Chemical Engineering, Food Science
Published: 2023

33. Immunosuppressive therapy and oral anticoagulation in kidney transplant recipients: Direct oral anticoagulants versus vitamin-k antagonists

Author: Francesco, Santoro, Annalisa, Casanova, Simona, Simone, Carlo, Alfieri, Adele, Falcone, Andrea, Dello Strologo, Valeria, Grandinetti, Marco, Busutti, Giorgia, Comai, Tommaso Maria, Marvulli, Maria Grazia, Zippo, Giuseppe, Castellano, Gaetano, La Manna, Loreto, Gesualdo, Grandaliano, Giuseppe, Francesco, Pesce, Giuseppe, Grandaliano (ORCID:0000-0003-1213-2177), Francesco, Santoro, Annalisa, Casanova, Simona, Simone, Carlo, Alfieri, Adele, Falcone, Andrea, Dello Strologo, Valeria, Grandinetti, Marco, Busutti, Giorgia, Comai, Tommaso Maria, Marvulli, Maria Grazia, Zippo, Giuseppe, Castellano, Gaetano, La Manna, Loreto, Gesualdo, Grandaliano, Giuseppe, Francesco, Pesce, and Giuseppe, Grandaliano (ORCID:0000-0003-1213-2177)
Abstract: Background: direct oral anticoagulants (DOACs) are an alternative to conventional antagonist of vitamin-K (AVK). However, immune suppressive drugs (ISDs) may interfere with DOACs pharmacokinetic. Aim of this study: evaluate safety and efficacy profile of DOACs compared to AVK in kidney transplant recipients (KTRs) treated with ISDs. Methods: a multi-center study from 4 Italian University hospitals enrolling consecutive KTRs on DOACs or AVK was carried out. Sixty-six patients on DOACs were compared with fifty patients on AVK with similar clinical features. Serial evaluation of renal function and serum levels of ISDs during 18 months follow-up (FU) was performed. Results: Mean age of DOACs patients was 67±9 and mean eGFR was 58,3± 30,4mL/min/1.73m2. ISDs included tacrolimus (n=47, 71%), cyclosporin (n=13, 20%), everolimus (n=10, 7%) and sirolimus (n=4, 6%). After 14 days of DOACs therapy initiation there was a slight increase of serum levels of tacrolimus (+0.19±0.67 p=0.80) and cyclosporine (+0.12±0.25 p=0.94) not statistically significant. Levels of Tacrolimus and cyclosporin were stable at serial evaluation during 18-months follow-up. There were no thromboembolic events among patients treated with DOACs or AVK and no differences in term of major bleeding (6% vs 4% p=0.69), at long-term follow-up. There was no difference in term of eGFR decline from start therapy to 18 months FU between DOACs vs AVK therapy (-3.9±1 vs -3.8±2 p=0.82). Conclusion: DOACs have similar safety and efficacy than AVK among KTRs treated with ISDs. However, careful evaluation of potential drug interaction and ISDs serum levels is needed.
Published: 2023

34. Conformational ensembles of the human intrinsically disordered proteome: Bridging chain compaction with function and sequence conservation

Author: Giulio Tesei, Anna Ida Trolle, Nicolas Jonsson, Johannes Betz, Francesco Pesce, Kristoffer E. Johansson, and Kresten Lindorff-Larsen
Abstract: Intrinsically disordered proteins and regions (collectively IDRs) are pervasive across proteomes in all kingdoms of life, help shape biological functions, and are involved in numerous diseases. IDRs populate a diverse set of transiently formed structures, yet defy commonly held sequence-structure-function relationships. Recent developments in protein structure prediction have led to the ability to predict the three-dimensional structures of folded proteins at the proteome scale, and have enabled large-scale studies of structure-function relationships. In contrast, knowledge of the conformational properties of IDRs is scarce, in part because the sequences of disordered proteins are poorly conserved and because only few have been characterized experimentally. We have developed an efficient model to generate conformational ensembles of IDRs, and thereby to predict their conformational properties from sequence only. Here, we applied this model to simulate all IDRs of the human proteome. Examining conformational ensembles of 29,998 IDRs, we show how chain compaction is correlated with cellular function and localization, including in different types of biomolecular condensates. We train a model to predict compaction from sequence and use this to show conservation of structural properties across orthologs. Our results recapitulate observations from previous studies of individual protein systems, and enable us to study the relationship between sequence, conservation, conformational ensembles, biological function and disease variants at the proteome scale.
Published: 2023

35. Is there a role in acute kidney injury for FGF23 and Klotho?

Author: Deborah Mattinzoli, Paolo Molinari, Gregorio Romero-González, Jordi Bover, Elisa Cicero, Francesco Pesce, Matteo Abinti, Costanza Conti, Giuseppe Castellano, and Carlo Alfieri
Subjects: Transplantation, Nephrology
Abstract: Cardio-renal syndrome is a clinical condition that has recently been well defined. In acute kidney disease, this interaction might trigger chronic processes determining the onset of cardiovascular events and the progression of chronic kidney disease. Moreover, the high mortality rate of AKI is also linked to the fact that this condition is often complicated with dysfunctions of other organs such as lungs, heart, or is associated to septic episodes. In this context the role and the potential link between bone, heart and kidney is becoming an important topic of research. The aim of this review is to describe the cardiac alterations in the presence of AKI (cardiorenal syndrome type 3) and explore how bone can interact with heart and kidney in determining and influencing the trend of AKI in the short and long term. The main anomalies of mineral metabolism in patients with AKI will be reported, with specific reference to the alterations of Fibroblast Growth factor 23 (FGF23) and Klotho as a link between bone-kidney-heart axis.
Published: 2023

36. Comparative Analysis of Different Methodologies to Calculate Lambda (λ) Based on Extensive And systemic Experimentation on a Hydrogen Internal Combustion Engine

Author: Naqash Azeem, Carlo Beatrice, Alberto Vassallo, Francesco Pesce, Gessaroli Davide, Chiara Guido, and Riccardo Rossi PhD
Abstract: Hydrogen Internal Combustion Engines (H2-ICEs) are subject to increased attention thanks to their extremely low criteria pollutant emission and near-zero CO2 tailpipe emissions. However, to further minimize exhaust emissions and increase the efficiency of a H2-ICE, it is important to carefully control the relative air-fuel ratio of operation, i.e. Lambda (λ), which will lead in turn to an optimal combustion process. The precise λ control mainly relies upon the methodology to calculate λ on board of the engine, where the availability of reliable sensors specifically-developed for hydrogen combustion is currently limited. In this article, a comparative analysis of different methodologies for the calculation of λ is performed, comparing four methodologies: exhaust gas analysis through a Spindt-Brettschneider approach (λEMI), raw Universal Exhaust Gas Oxygen (λR-UEGO), processed Universal Exhaust Gas Oxygen (λP-UEGO) and speed-density (λSD) outputs. The experimental data used to compare the four methodologies were acquired through detailed and systematic experimentation on a fully-instrumented single-cylinder H2-ICE. Results show that the λP-UEGO is the closest one to the reference Spindt-Brettschneider analysis λEMI and the most robust to ample variations in the nominal λ values. The sensor’s raw UEGO output λR-UEGO is instead affected by the sensor calibration which is usually performed across a range of carbon-based fuels, a procedure that introduces a bias. The results can be used for the selection of the correct methodology to calculate λ in a H2-ICE and to choose optimal sensors for mobile applications.
Published: 2023

37. Combining experiments and simulations to examine the temperature-dependent behaviour of a disordered protein

Author: Francesco Pesce and Kresten Lindorff-Larsen
Abstract: Intrinsically disordered proteins are a class of proteins that lack stable folded conformations and instead adopt a range of conformations that determine their biochemical functions. The temperature-dependent behaviour of such disordered proteins is complex and can vary depending on the specific protein and environment. Here, we have used molecular dynamics simulations and previously published experimental data to investigate the temperature-dependent behaviour of Histatin 5, a 24-residue-long polypeptide. We examined the hypothesis that Histatin 5 undergoes a loss of polyproline II structure with increasing temperature, leading to more compact conformations. We found that the conformational ensembles generated by the simulations generally agree with small-angle X-ray scattering data for Histatin 5, but show some discrepancies with the hydrodynamic radius as probed by pulsed-field gradient nuclear magnetic resonance spectroscopy, and with the secondary structure information derived from circular dichroism. We attempted to reconcile these differences by reweighting the conformational ensembles against the scattering and NMR data. By doing so, we were in part able to capture the temperature-dependent behaviour of Histatin 5 and to link the observed decrease in hydrodynamic radius with increasing temperature to a loss of polyproline II structure. We were, however, unable to achieve agreement with both the scattering and NMR data within experimental errors. We discuss different possibilities for this outcome including inaccuracies in the force field, differences in conditions of the NMR and scattering experiments, and issues related to the calculation of the hydrodynamic radius from conformational ensembles. Our study highlights the importance of integrating multiple types of experimental data when modelling conformational ensembles of disordered proteins and how environmental factors such as the temperature influence them.
Published: 2023

38. GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art

Author: Antonio Granata, Rosario Maccarrone, Massimiliano Anzaldi, Giuseppe Leonardi, Francesco Pesce, Francesco Amico, Loreto Gesualdo, Salvatore Corrao, Granata A., Maccarrone R., Anzaldi M., Leonardi G., Pesce F., Amico F., Gesualdo L., and Corrao S.
Subjects: nephroprotection, Transplantation, GLP-1 receptor agonist, Nephrology, albuminuria, COVID-19 disease, diabetic kidney disease
Abstract: Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are highly effective in improving glycaemic control either as monotherapy or in combination with other hypoglycaemic drugs, and have low incidence of side effects, such as hypoglycaemia, nausea and weight gain, thus increasing patients' adherence to therapy. Methods In this review we report the most recent studies demonstrating the beneficial effects of GLP-1RAs on renal outcomes, and also discuss the direct and indirect mechanisms through which they confer kidney protection. Finally, we discuss the metabolic and anti-inflammatory effects of GLP-1RAs in diabetic patients with COVID-19 disease. Results GLP-1RAs have a nephroprotective action, which is expressed through both indirect (improvement of blood pressure and glycaemic control, weight loss) and direct (restoration of normal intrarenal haemodynamics, prevention of ischaemic and oxidative damage) effects. They have shown also metabolic and anti-inflammation beneficial effects in patients with COVID-19 disease. Conclusions GLP-1RAs prevent albuminuria and slow the decline of renal function towards end stage renal disease in patients with diabetic kidney disease. They might be an opportunity to break the typical inflammation processes of COVID-19 disease.
Published: 2022

39. Contrast-enhanced ultrasound in peritoneal dialysis: when and how to perform it

Author: Granata Antonio, Francesco Pesce, and Loreto Gesualdo
Subjects: Nephrology
Published: 2022

40. Immune abnormalities in IgA nephropathy

Author: Micaela Gentile, Luis Sanchez-Russo, Leonardo V Riella, Alberto Verlato, Joaquin Manrique, Simona Granata, Enrico Fiaccadori, Francesco Pesce, Gianluigi Zaza, and Paolo Cravedi
Subjects: Transplantation, Nephrology
Abstract: Immunoglobulin A (IgA) nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and it is characterized by mesangial IgA deposition. Asymptomatic hematuria with various degrees of proteinuria is the most common clinical presentation and up to 20%–40% of patients develop end-stage kidney disease within 20 years after disease onset. The pathogenesis of IgAN involves four sequential processes known as the “four-hit hypothesis” which starts with the production of a galactose-deficient IgA1 (gd-IgA1), followed by the formation of anti-gd-IgA1 IgG or IgA1 autoantibodies and immune complexes that ultimately deposit in the glomerular mesangium, leading to inflammation and injury. Although several key questions about the production of gd-IgA1 and the formation of anti-gd-IgA1 antibodies remain unanswered, a growing body of evidence is shedding light on the innate and adaptive immune mechanisms involved in this complex pathogenic process. Herein, we will focus on these mechanisms that, along with genetic and environmental factors, are thought to play a key role in disease pathogenesis.
Published: 2023

41. Empagliflozin in Patients with Chronic Kidney Disease

Author: Herrington, William G, Staplin, Natalie, Wanner, Christoph, Green, Jennifer B, Hauske, Sibylle J, Emberson, Jonathan R, Preiss, David, Judge, Parminder, Mayne, Kaitlin J, Ng, Sarah Y A, Sammons, Emily, Zhu, Doreen, Hill, Michael, Stevens, Will, Wallendszus, Karl, Brenner, Susanne, Cheung, Alfred K, Liu, Zhi-Hong, Li, Jing, Hooi, Lai Seong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Maggioni, Aldo P, Pontremoli, Roberto, Deo, Rajat, Goto, Shinya, Rossello, Xavier, Tuttle, Katherine R, Steubl, Dominik, Petrini, Michaela, Massey, Dan, Eilbracht, Jens, Brueckmann, Martina, Landray, Martin J, Baigent, Colin, Haynes, Richard, The EMPA-KIDNEY Collaborative Group: Colin Baigent, Martin J Landray, Christoph Wanner, William G Herrington, Richard Haynes, Jennifer B Green, Sibylle J Hauske, Martina Brueckmann, Mark Hopley, Maximillian von-Eynatten, Jyothis George, Susanne Brenner, Alfred K Cheung, David Preiss, Zhi-Hong Liu, Jing Li, Laiseong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Roberto Pontremoli, Aldo P Maggioni, Natalie Staplin, Jonathan Emberson, Stefan Hantel, Shinya Goto, Rajat Deo, Katherine R Tuttle, Michael Hill, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Xavier Rossello, Emily Sammons, Doreen Zhu, Peter Sandercock, Rudolf Bilous, Charles Herzog, Paul Whelton, Janet Wittes, Derrick Bennett, Patricia Achiri, Chrissie Ambrose, Cristina Badin, Jill Barton, Richard Brown, Andy Burke, Sebastian Butler, Rejive Dayanandan, Pia Donaldson, Robert Dykas, Lucy Fletcher, Kate Frederick, Hannah Kingston, Mo Gray, Emily Harding, Akiko Hashimoto, Lyn Howie, Susan Hurley, Ryonfa Lee, Nik Luker, Kevin Murphy, Mariko Nakahara, John Nolan, Michelle Nunn, Sorcha Mulligan, Akiko Omata, Sandra Pickworth, YanRu Qiao, Shraddha Shah, Karen Taylor, Alison Timadjer, Monique Willett, Liz Wincott, Qin Yan, Hui Yu, Louise Bowman, Fang Chen, Robert Clarke, Michelle Goonasekera, Waseem Karsan, Marion Mafham, Christina Reith, Mohammed Zayed, Ritva Ellison, Rowan Moys, Will Stevens, Kevin Verdel, Karl Wallendszus, Chris Bowler, Anna Brewer, Andy Measor, Guanguo Cui, Charles Daniels, Angela Field, Bob Goodenough, Ashley Lawson, Youcef Mostefai, Dheeptha Radhakrishnan, Samee Syed, Shuang Xia, Ruth Adewuyi-Dalton, Thomas Arnold, Anne-Marie Beneat, Anoushka Bhatt, Chloe Bird, Andrew Breach, Laura Brown, Mark Caple, Tatyana Chavagnon, Karen Chung, Sarah Clark, Luminita Condurache, Katarzyna Eichstadt, Marta Espino Obrero, Scarlett Forest, Helen French, Nick Goodwin, Andrew Gordon, Joanne Gordon, Cat Guest, Tina Harding, Michal Hozak, Matthew Lacey, David MacLean, Louise Messinger, Stewart Moffat, Martin Radley, Claire Shenton, Sarah Tipper, Jon Tyler, Lesley Weaving, James Wheeler, Elissa Williams, Tim Williams, Hamish Woodhouse, Angela Chamberlain, Jo Chambers, Joanne Davies, Denise Donaldson, Pati Faria-Shayler, Denise Fleming-Brown, Jennifer Ingell, Carol Knott, Anna Liew, Helen Lochhead, Juliette Meek, Isabel Rodriguez-Bachiller, Andrea Wilson, Patrick Zettergren, Rach AitSadi, Ian Barton, Alex Baxter, Yonghong Bu, Lukasz Danel, Sonja Grotjahn, Rijo Kurien, Michael Lay, Archie Maskill, Aleksandra Murawska, Rachel Raff, Allen Young, Rebecca Sardell, Vladimir Cejka, Marcela Fajardo-Moser, Christian Hartner, Doris Poehler, Janina Renner, Franziska Scheidemantel, Miya Bryant, Anita Hepditch, Cassandra Johnson, Erin Latore, Yolanda Miller, Lauren Price, Merilee Whalen, Ashleigh Wheeler, Jenny Ingell, Yu An, Yinghua Chen, Peiling Chen, Hao Dai, Hong Du, Fang Feng, Qing Guo, Libo Hou, Wuhanbilige Hundei, Binbin Jin, Yan Li, Jiamin Liu, Xia Song, Yanping Wang, Yanwu Yu, Ning Zhang, Lingshan Zhao, Hui Zhong, Cheng Beng Goh, Ye Mun Low, Soon Yi Sor, Farah Hanis Zulkipli, Sarojini Sivanandam, Natsuki Arai, Ai Fukasawa, Mizue Furukawa, Keisuke Habuki, Shoko Hayashi, Wakako Isari, Saki Kanegae, Maria Kawai, Reiki Kobayashi, Takako Kuramae, Chika Kuribayashi, Sawako Maeno, Satoshi Masumoto, Tomoko Morisaki, Minoru Oda, Kazue Sawada, Kenta Sugamori, Ayana Tatsuzawa, Aiko Tomita, Kazuyuki Yuasa, Hiroko Inazawa, Amanda Axler, Kerri Gallo, Ester Baldini, Barbara Bartolomei Mecatti, Francesca Bianchini, Martina Ceseri, Laura Cipressa, Gianna Fabbri, Andrea Lorimer, Donata Lucci, Sharang Ghavampour, Anja Knoppe, Hans Schmidt-Gurtler, Hubert Dumann, Sybille Merscher, Margret Patecki, Georg Rainer Schlieper, Anke Torp, Bianca Weber, Maja Zietz, Bernd Hohenstein, Urs Benck, Diliana Draganova, Thomas Weinreich, Lothar Wolf, Jasmine Gaidu, Hanna Reiner, Mandy Visnjic, Daniel Steffl, Marie Breitenfeldt, Annette Kraemer-Guth, Christine Braun, Simone Hagge, Michael Schomig, Stephan Matthias, Dominik Stoffler, Beate Schumacher, Thomas Sitter, Louise Fuessl, Julia Krappe, Jerome Loutan, Volker Vielhauer, Luciano Andriaccio, Magdalena Maurer, Bernhard Winkelmann, Martin Dursch, Linda Seifert, Linda Tenbusch, Julia Weinmann-Menke, Simone Boedecker, Wiebke Kaluza-Schilling, Daniel Kraus, Carina Krieger, Margit Schmude, Anne Schreiber, Ewelina Eckrich, Diethelm Tschope, Abdulwahab Arbi, Young Lee-Barkey, Bernd Stratmann, Natalie Prib, Sina Rolfsmeier, Irina Schneider, Lars Rump, Johannes Stegbauer, Christine Pötz, Mara Schemmelmann, Claudia Schmidt, Michael Koch, Sendogan Aker, Annika Küpper, Manuela Martin, Thiemo Pfab, Christian Albert, Michael Haase, Barbara Zander, Claudia Schneider-Danwitz, Wolfgang Seeger, Wolf-Adam Seeger, Britta Zemann, Christoph Stellbrink, Kristin Marx, Ekaterina Stellbrink, Britta Brettschneider, Stephanie Watson, Marion Iselt, Gerhard Klausmann, Inga-Nadine Kummer, Auguste Kutschat, Simone Streitenberger, Matthias Girndt, Silke Markau, Ina Girakossyan, Claudia Hanf, Joachim Beige, Ralph Wendt, Ulrike Schmidt, Andreas Schneider, Roland Veelken, Claudia Donhauser, Luis Becker, Nexhat Miftari, Ricarda Wolfling, Sarah Morlok, Christian Hugo, Alexander Paliege, Jens Passauer, Julian Stumpf, Annegret Fleischer, Kerstin Haaser, Bernhard Kraemer, Jan Jochims, Bernd Kruger, Claudia Foellinger, Anastassiya Reisler, Frank Strutz, Stefan Haack, Ursula Hohenstatt, Martin Busch, Konstantin Herfurth, Gunter Wolf, Rainer Paul, Hermann Haller, Jessica Kaufeld, Jan Menne, Elisabeth Bahlmann-Kroll, Angela Bergner, Horst Weihprecht, Aydin Er, Florian Sonntag, Elif Turan, Michael Wittmann, Franziska Klauser, Eva Voigt, Volker Schettler, Egbert Schulz, Madlen Rohnstock, Elke Schettler, Bernd Schroppel, Rene van Erp, Martin Kachele, Ulla Ludwig, Lena Schulte-Kemna, Waltraud Kmietschak, Elke Preiss, Martina Ruocco, Gunnar Heine, Martin Brzoska, Sebastian Gabel, Christina Büttner, Asma Sabarai, Bernhard Banas, Tobias Bergler, Yvonne Ehrl, Franz Putz, Antonia Schuster, Stefanie Kuhn, Torsten Schramm, Stefan Degenhardt, Gerhard Schmidt, Lea Weiland, Ulrike Giebeln-Hudnell, Jan Kielstein, Gabriele Eden, Brigitte Fuchs, Gina Morig, Manuela Winkler, Harald Darius, Charalampos Kriatselis, Carl-Philipp Roesch, Astrid Maselli, Dominik Alscher, Markus Ketteler, Moritz Schanz, Severin Schricker, Bianka Rettenmaier, Andrea Schwab, Pablo Pergola, Irene Leal, Melissa Cagle, Anna Romo, Anthony Torres, Sucharit Joshi, Kulli Barrett, Alexis Africano, Vicki Dodds, Dorleena Gowen, Ashlee Morris, Juan Fernandez, Guillermo Jimenez, Ricardo Viera, Kendaling Bruce, Ryan Barrios, Maylin Garcia, Kerelyn Garcia, Iradis Leal, David Tietjen, David Bains, Carlo Castillo, Genielle Brewer, Justin Davis, Natalie Freking, Brittany Golson, Sally Ham, Jesslyn Roesch, Pusadee Suchinda, Shameem Beigh, Usah Lilavivat, Joyce Bilton, Kim Bocchicchia, Jeffrey Turner, Neera Dahl, Aldo Peixoto, Yasemin Kavak, Lauren Liberti, Hari Nair, Nicolas Page, Stephanie Rosenberg, Kathryn Simmons, Tamara Isakova, Rebecca Frazier, Rupal Mehta, Anand Srivastava, Patrick Fox, Jonathan Hecktman, Alexander Hodakowski, Carlos Martinez, Rachel Phillips, Alexis Stevenson, Reem Mustafa, Kyle Jansson, Cassandra Kimber, Jason Stubbs, Ahmad Tuffaha, Sri Yarlagadda, Debbie Griffin, Elisabeth Laundy, Zhuo Tang, Radica Alicic, Ann Cooper, Lisa Davis, Ashwini Gore, Rebecca Goldfaden, Leslie Harvill, Lisa Hichkad, Barry Johns, Thomas Jones, Kayla Merritt, Jennifer Sheldon, Jennifer Stanfield, Lindsay Alexander, Kaitlyn Preston, Lindsey Wood, Rajesh Pradhan, Roger DeRaad, Kelli McIntosh, Louis Raymond, Michael Shepperd, Susan McLaughlin, Mary Seifert, Andrew Shepherd, Joseph Aiello, William Durham, Laurie Loudermilk, John Manley, Sabrina Burnette, Stephanie Evans, Tara Johnson, Lance Sloan, Judy Ann Acosta, Stacy Gillham, Katia Sloan, SueAnn Squyres, Michael Rocco, Amret Hawfield, Ben Bagwell, Lauren Richmond, Joseph Soufer, Subha Clarke, Amanda Aliu, Kristine Calabrese, Amanda Davis, Veronica Poma, Tracy Spinola, James Magee, Ricardo Silva, Rushab Choksi, Lorraine Dajani, John Evans, Anil George, Prasanth Krish, Gerard Martins, Mae Sheikh-Ali, David Sutton, Freda Driver, Abraham Hanburry, Laura Hume, Amber Hurst, Matthew Taddeo, Marla Turner, Veronica Yousif, Srinivasan Beddhu, Laith Al-Rabadi, Nikita Abraham, Amalia Caamano, Judy Carle, Victoria Gonce, Kaitlyn Staylor, Na Zhou, Shweta Bansal, Manoj Bhattarai, Kumar Sharma, Subrata Debnath, Aliseiya Garza, Chakradhar Velagapudi, Sergio Rovner, Javier Almeida, Pablo Casares, Verlaine Stewart-Ray, Rene Almaraz, Renata Dayrell, Ana Moncada, Ricardo Pulido, Roxana Rodriquez, Wasim Deeb, Kathryn DeGoursey, Rodel Gloria, Trevor Greene, Robert Miller, Edward Pereira, Miguel Roura, Debbie Domingo, Sasha Dorestin, William Hodge, Cathy Jackson, Deborah Lund, Katrina Taylor, Kenneth Boren, Brittany Cleveland, Sandra Gaiser, Mandeep Sahani, Logan Aldrich, Exodus Edmerson, Edmond Limon, Cole Valletta, Patricia Vasquez, Christopher Provenzano, Navkiranjot Brar, Heather Henderson, Bellovich Keith, Qur Khai, Quresh Khairullah, Gail Makos, Joel Topf, Sherry Gasko, Rosemarie Henschel, Kaitlin Knapp, Teresa Kozlowski, Paula LaFleur, Ashwathy Varughese, Hui Xue, Patricia Wu, Olga Arechiga, Shan Darbeau, Michael Fechter, Stephanie Martinez, Lenita Hanson, Nyla Cooper, Arelis Madera, Jay Cadorna, Rita Sheridan, Helen Sparks, Bradley Eilerman, Susanne Bodine, Wael Eid, Rebecca Flora, Amber Avery, Cashmere Hardy, Mihaela Biscoveanu, Steven Nagelberg, Tracey Cummins, Frederic Rahbari-Oskoui, Anju Oommen, Zohreh Forghani, Stacie Hitchcock, Darya Hosein, Diane Watkins, Minesh Patel, Anthony Lambert, Elizabeth Newman, Autumn Wood, Tammy Ross, Stephany Topping, Jeffrey Mulhern, Lorna Murphy, Ann Vasseur, Gregory Greenwood, Alexander Hadley, Denise Laurienti, Christopher Marshall, Nicholas McLean, Scott Satko, Brandy Caudill, Jacob Maris, Janice Rogers, Cindy Vanhoy, George Thomas, Georges Nakhoul, John O'Toole, Jonathan Taliercio, Leslie Cooperman, Marina Markovic, Barbara Tucky, Devasmita Dev, Alia Hasan, Hima Yalamanchili, Namita Jain, Lesley McNeil, Eric Wines, Jean Park, Adline Ghazi, Mia Hamm, Tejas Patel, Amy Mottl, Emily Chang, Vimal Derebail, Emmie Cole, Anne Froment, Sara Kelley, Jordan Osmond Foster, Vahid Mahabadi, Golriz Jafari, Anita Kamarzarian, Wendy Arriaga, Daisy Arteaga, Rosario Machicado, Genesis Naverrete, Prashant Kumar, Imran Nazeer, Karina Urquia, Tammi Glider, Vickie Jones, Savannah Rucker, Jennifer Wiley, Rahul Pandey, Jesus Arroyo, Harish Pariani, Mohammad Ahmad, Shahin Mozaffari, Erika Perez, Matthew Budoff, Sion Roy, Divya Birudaraju, Ahmed Ghanem, Sajad Hamal, Stephen Aronoff, Elisa Joye Petr, Richard Sachson, Jaime Wiebel, Sana Akram, Laurie Jones, Curtis Knight, Maurie Tarlac, Shahbaz Ahmed, Harold Szerlip, Akinwande Akinfolarin, Ankit Mehta, Shana Camp, Cindy Castro, Zanaida Cooper, Jessica Terry, Ahmed Awad, Bhavya Kothapalli, Ryan Lustig, Serine Alfaress, Hyder Jasim, Mary Parrigon, Dennis Karounos, Sadiq Ahmed, Maggie Berry, Ruth Oremus, Carlos Hernandez-Cassis, Elias Ugwu, Nazia Junejo, Nancy Suazo, Mark Segal, Amir Kazory, Sherry Brown, Tristan Daniels, Sofia Dayi, Renee Hogan, Kathy McCray, Jennifer Stickley, Mahboob Rahman, Mirela Dobre, Lavinia Negrea, Aparna Padiyar, Nishigandha Pradhan, Arash Rashidi, Nagaraju Sarabu, Vicki Donley, Tricia Young, Godson Oguchi, Judepatricks Onyema, Kahla Damianik, Jack Dienes, Judith Plummer-Morgan, Marilyn Roman, Mauver Skipper, Stacey-Ann Villaruel, Krystle Williams, Danny Sugimoto, Jeffrey Dugas, Ismeal Ahmed, Jamie Bhairoo, Dolores Rijos, Huzaifa Salim, Madita Gavrila, Kathryn Lafferty, Ria Rabara, Sally Ruse, Maria Weetman, James Bushnell, Albert Power, Alison Jenkins, Stefanie Jones, Amanda Scott, Cath Byrne, Mark Jesky, Alison Cowley, Emma McHaffie, Holly Waterfall, Jo Taylor, Laura Bough, Thomas Phillips, Barbara Winter-Goodwin, Sui Phin Kon, Iain MacDougall, Eirini Lioudaki, Sapna Shah, Claire Sharpe, Francisco Aguilar, Abegail Hernandez Pena, Conception Pugay, Amelia Te, Hugh Finn, Wasim Hanif, Samiul Mostafa, Alice Aitken, Katharine Draxlbauer, Evelina Grobovaite, Jennifer Kearney, Theresa McCarthy, Giorgio Gentile, Duncan Browne, Palanichamy Chellamuthu, Tabinda Dugal, Terri Chant, Laura Jones, Emily Laity, Megan Miners, James Muir, Elizabeth Swanson, Andrew Frankel, James Tomlinson, Marlon Alegata, Rashid Almasarwah, Anthoula Apostolidi, Maria Vourvou, Thomas Walters, Maarten Taal, Hari Dukka, Nitin Kolhe, Carly McDonald, Kelly White, Shiva Ugni, Smita Gunda, Rotimi Oluyombo, Vicki Brindle, Ping Coutts, Tracy Fuller, Evelyn Nadar, Suresh Ramadoss, Nichola Motherwell, Susannah Pajak, Louise Tonks, Sunil Bhandari, Richard Bodington, Adil Hazara, Dominic Fellowes, Christopher Wong, Christopher Goldsmith, Sherald Barnes, Ann Bennett, Claire Burston, Samantha Hope, Nicola Hunt, Lini Kurian, Richard Fish, Daniela Farrugia, Judy Lee, Emma Sadler, Hannah Turner, Christopher Hill, Henry Brown, Agnes Masengu, Peter Maxwell, Nina Bleakley, Hugh Murtagh, William Petchey, Vivian Yiu, Joanne Kellett, Angharad Williams, Helen Clarke, Victoria Carnall, Sarah Benyon, Caroline Blake, Stephanie Estcourt, Jane Piper, Neal Morgan, Carolyn Hutchinson, Teresa McKinley, Alastair Woodman, Judi Graham, Niall Leonard, John Smyth, Vicki Adell, Samantha Hagan, Ben Caplin, Amin Oomatia, Eleanor Damian, Toluleyi Sobande, Tim Doulton, Michael Delaney, Mahmoud Montasser, Jenny Hansen, David Loader, Angela Moon, Frances Morris, Smeeta Sinha, Chukwuma Chukwu, Amy Hudson, Diane Campbell, Melanie Kershaw, Stephanie Whittaker, Ayesha Irtiza-Ali, Farid Ghalli, Heba Nosseir, Allison Leslie, Kate Trivedi, Donald Fraser, Mohammad Alhadj Ali, Sian Griffin, Farah Latif, Justyna Witczak, Alexa Wonnacott, Lynda Jeffers, Yvette Webley, Paul Phelan, Eve Miller-Hodges, Ailsa Geddes, Margaret Glenwright, Amy Hunter, Thomas Pickett, Jim Moriarty, Linda Hill, Amanda Tyler, Waqar Ayub, Gail Evans, Sue Hewins, Davina Hewitt, Kerry Read, Samira Bell, Leanne Cosgrove, Rachel Craik, Shona Murray, Nitin Bhandary, Holly Coles, Rashmi Easow, Maya Joseph, Arif Khwaja, Yvonne Jackson, Angeline Mbuyisa, Rachel Sellars, Nihil Chitalia, Cynthia Mohandas, Anca Gherman, Charlotte Kamundi, Olumide Olufuwa, Kieran McCafferty, Adedolapo Adeleke, Cara Healy, Damini Jeyarajah, Edward Kinsella-Perks, Richard Smith, Brian Camilleri, Carol Buckman, Jenny Finch, Vanessa Rivers, Andrew Connor, Sheila Carr, Lisa Shainberg, Andrew Lewington, Richard Baker, Suzannah Dorey, Kay Tobin, Rosalyn Wheatley, Debasish Banerjee, Richard Hull, Sharirose Abat, Riny Paul, Mahzuz Karim, Zay Htet, Saad Tufail, Ravi Varma, Karen Convery, Deirdre Fottrell-Gould, Lisa Hudig, Emily Tropman, Thahir Abdul-Samad, Anne Grace, Marie Phipps, Rebecca Suckling, Subash Somalanka, Bhrigu Sood, Pauline Swift, Sarah Acheampong, Kwame Ansu, Martia Augustin, Anna Sampson, Lynn Vinall, Kim Wren, Shamila Wanninayake, Nicholas Wooding, Heather Edwards, Lydia Owen, Stephanie Bolton, Marion Carson, Michael Matthews, Nigel Brunskill, Jorge Jesus-Silva, Alex Howson, Mary Quashie-Akponeware, Hilary Tindall, Chidambaram Nethaji, Helen Eldon, Rajan Patel, Patrick Mark, Alastair Rankin, Michael Sullivan, Kirsty Forsyth, Rowan McDougall, Tanaji Dasgupta, Louisa Davies, Maggie Ryder, Philip Grimmer, Clare Macdonald, Mary Webster, Newcastle Newcastle, Timothy Ellam, Edwin Wong, Christine Meshykhi, Andrea Webster, Peter Wilson, Enric Vilar, Jocelyn Berdeprado, Eunice Doctolero, Lily Wilkinson, Frank McCarroll, Hesham Ammar, Ying Kuan, Conor Moran, Girish Shivashankar, Ryan Campbell, Deborah Glowski, Paula McDermott, Amar Ali, Zuber Patel, Christine Bond, Gillian Whalley, Haitao Zhang, Liu Yang, Lihua Zhang, Tingting Kan, Ling Zhu, Jinghong Zhao, Weiping Hou, Jing Wu, Hong Cheng, Weijing Bian, Zhirui Zhao, Fengmin Shao, Huixia Cao, Xiaojing Jiao, Peiyuan Niu, Jianying Niu, Yu Chen, Lihong Zhang, Shenglang Zhu, Haiyan Lin, Shaopeng Yao, Jiehui Chen, Ying Jiang, Ying Hu, Huaying Xiao, Fuye Yang, Xinzhou Zhang, Baochun Guo, Qiu Jin, Lixia Liu, Xiangcheng Xiao, Yanyun Xie, Ting Meng, Chuanwen Xu, Jie Huang, Yanmei Xu, Weixin Kong, Xiaoliang Wang, Qianpan Liu, Xueying Wang, Ming Gao, Xiumei Hu, Ying Lu, Li Wang, Kun Peng, Wei Wang, Qiuhong Gong, Jianfang Cai, Xiaojue Li, Xuejiao Liu, Shuhan Zhou, Hong Liu, Yao Weng, Shuai Tang, Yao Yao, Shi Zhao, Chen Cheng, Wei Wei, Na Li, Sadanah Aqashiah Mazlan, Alia Zubaidah Bahtar, Elliyyin Katiman, Noraini Othman, Lily Mushahar, Nurdiana Mazlan, Nur Sharafina Safiee, Sarasa Ramasamy, Hin Seng Wong, Hajar Ahmad Rosdi, Esther Zhao Zhi Tan, Ju Fan Tay, Kok Seng Teng, Hasnah Yahaya, Wen Jiun Liu, Lik Wee Ee, Kenneth Kay Leong Khoo, Yuana Mohd Yusoff, Fariz Safhan Mohamad Nor, Mohd Kamil Ahmad, Mohd Ramli Seman, Clare Hui Hong Tan, Laura Lui Sian Ngu, Jaime Yoke May Chan, Javelin Peji, Chek Loong Loh, Yee Yan Lee, Sridhar Ramanaidu, Kah Mean Thong, Yik Hong Wong, Suria Junus, Chen Hua Ching, Mohammad Faisal Asmee, Ku Ruziana Ku Md Razi, Chun Leong Low, Christopher Sze Bing Sim, Zhang Duan Tham, Noor Kamila Abdullah, Tai Meng Chen, Yong Chieh Chan, Eason Chang, Huan Yean Kang, Kai Quan Lee, Sue Ann Lee, Aik Kheng Lee, Jeevika Vinathan, Rizna Abdul Cader, Ruslinda Mustafar, Lydia Kamaruzaman, Rozita Mohd, Rahimah Ismail, Chong Men Leong, Chee Koon Low, Liang Wei Wong, Norlezah Adnan, Sabariah Ibrahim, Mohamad Zaimi Abdul Wahab, Sunita Bavanandan, Yik Shen Lim, Wan Hazlina Wan Mohamad, Siti Munirah Jaafar, Nur Ashykeen Mohd Fauzi, Aziee Sudin, Soo Kun Lim, Chye Chung Gan, Albert Hing, Wan Ahmad Faizal Alaidin Razali, Yew Fong Liew, Chelsia Bao Tyng Chan, Mei Chih Cheng, Yu Chen Ong, Loke Meng Ong, Farah Amalina Mohamed Affandi, Korina Rahmat, Ban Chai Peng, Masayu Amat, Nuzaimin Hadafi Ahmad, Doo Yee Mah, Yi Loon Tye, Zaid Azhari, Siti Nabilah Mohamad Zaini, Mohd Aidil Musa, Norazinizah Ahmad Miswan, Rafizanur Ramli, Nor Aziah Ahmad, Bak Leong Goh, Nurul Izah Ahmad, Fairol Huda Ibrahim, Tze Jian Ng, Malini Shanmuganathan, Li Lian Tay, Zaiha Harun, Salmi Ramli, Nurul 'Ain Yusof, Rossenizal Abd Rahman, Muhammad Iqbal Abdul Hafidz, Nur Hidayati Mohd Sharif, Irda Yasmoon Awang, Eitaro Nakashima, Rui Imamine, Makiko Minatoguchi, Yukari Miura, Miduki Nakaoka, Yoshiki Suzuki, Hitomi Yoshikawa, Koki Shin, Kanae Fujita, Misuzu Iwasa, Haruka Sasajima, Airi Sato, Yoshiyuki Hamamoto, Yuki Fujita, Takuya Haraguchi, Takanori Hyo, Kiyohiro Izumi, Toshiyuki Komiya, Sodai Kubota, Takeshi Kurose, Hitoshi Kuwata, Susumu Nakatani, Kaori Oishi, Saki Okamoto, Kaori Okamura, Jun Takeoka, Nagaaki Tanaka, Katsuya Tanigaki, Naohiro Toda, Koin Watanabe, Hiromi Komori, Rika Kumuji, Asako Takesada, Aya Tanaka, Shoichi Maruyama, Tomonori Hasegawa, Akiko Ishiguro, Takuji Ishimoto, Kazuhiro Ito, Yutaka Kamimura, Noritoshi Kato, Sawako Kato, Hiroshi Kojima, Tomoki Kosugi, Kayaho Maeda, Masasi Mizuno, Shoji Saito, Hitomi Sato, Yuka Sato, Yasuhiro Suzuki, Akihito Tanaka, Yoshinari Yasuda, Fujiko Hasegawa, Maiko Hayashi, Shizuka Higashi, Kaho Shimamura, Momoko Sumi, Kazuki Tajima, Chimaki Unekawa, Kana Wakayama, Yukiko Wakita, Takatoshi Otani, Ayako Imai, Sayaka Kawashima, Eri Kogure, Tomoe Sato, Misato Takezawa, Shinya Yoshida, Hideo Araki, Yuko Katsuda, Masahiro Konishi, Takahiro Matsunaga, Masashi Oe, Kunihiro Ogane, Masato Sakai, Tomoko Takahashi, Takahiro Yamano, Takuya Yokoyama, Hitomi Ito, Masayo Katayama, Emi Kuroda, Toru Ikeda, Takuma Kojo, Etsuo Yoshidome, Rieko Mizumachi, Akane Yamamoto, Narihisa Yamasaki, Yoshihiko Yamasaki, Jun Wada, Jun Eguchi, Chigusa Higuchi, Akihiro Katayama, Masaru Kinomura, Masashi Kitagawa, Shinji Kitamura, Satoshi Miyamoto, Hiroshi Morinaga, Atsuko Nakatsuka, Ichiro Nojima, Kenichi Shikata, Hitoshi Sugiyama, Katsuyuki Tanabe, Kenji Tsuji, Haruhito Uchida, Mayu Watanabe, Chie Hashimoto, Takahiro Kato, Sayaka Yamamoto, Takehiko Wada, Masafumi Fukagawa, Naoto Hamano, Masahiro Koizumi, Hirotaka Komaba, Yosuke Nakagawa, Michiyo Iwamoto, Kosuke Masutani, Akane Katanosaka, Mayu Kiyota, Hikari Uchi, Yuka Ueda, Sonoka Yamamoto, Hajime Nagasu, Seiji Itano, Tsukasa Iwakura, Hiroyuki Kadoya, Eiichiro Kanda, Naoki Kashihara, Kengo Kidokoro, Megumi Kondo, Tamaki Sasaki, Minoru Satoh, Atsuyuki Tokuyama, Reina Umeno, Yoshihisa Wada, Toshiya Yamamoto, Yu Yamanouchi, Masumi Abe, Yoko Inukai, Wataru Ogawa, Shunichiro Asahara, Hideki Fujii, Shunsuke Goto, Yushi Hirota, Tetsuya Hosooka, Keiji Kono, Shinichi Nishi, Yuko Okada, Kazuhiko Sakaguchi, Kenji Sugawara, Michiko Takahashi, Tomoko Takai, Yoshikazu Tamori, Kentaro Watanabe, Miyu Kitajima, Misaki Nishi, Junko Wada, Yasuhiko Ito, Hideki Kamiya, Akimasa Asai, Nao Asai, Saeko Asano, Shogo Banno, Yohei Ejima, Hanako Hase, Tomohide Hayami, Tatsuhito Himeno, Takahiro Ishikawa, Mayumi Ito, Shiho Iwagaitsu, Rina Kasagi, Yoshiro Kato, Makoto Kato, Koichi Kato, Takayuki Katsuno, Miyuka Kawai, Hiroshi Kinashi, Masaki Kondo, Masako Koshino, Naoya Matsuoka, Yoshiaki Morishita, Mikio Motegi, Jiro Nakamura, Hiromi Shimoda, Hirokazu Sugiyama, Shin Tsunekawa, Makoto Yamaguchi, Kazuyo Takahashi, Hirotaka Watada, Takashi Funayama, Yasuhiko Furukawa, Tomohito Gohda, Hiromasa Goto, Hideyoshi Kaga, Yasuhiko Kanaguchi, Akio Kanazawa, Kayo Kaneko, Toshiki Kano, Masao Kihara, Shogo Kimura, Takashi Kobayashi, Masayuki Maiguma, Yuko Makita, Satoshi Mano, Tomoya Mita, Takeshi Miyatsuka, Maki Murakoshi, Masahiro Muto, Masami Nakata, Junichiro Nakata, Yuya Nishida, Nao Nohara, Takeshi Ogihara, Daisuke Sato, Junko Sato, Hiroaki Sato, Yusuke Suzuki, Ruka Suzuki, Hitoshi Suzuki, Miyuki Takagi, Yoshifumi Tamura, Toyoyoshi Uchida, Seiji Ueda, Miki Asawa, Minako Miyaji, Eri Nagashima, Yoshie Shibata, Eri Yanagisawa, Toshimasa Yamauchi, Yosuke Hirakawa, Hiroshi Nishi, Nobuhiro Shojima, Satoko Horikawa, Yukiko Nakayama, Naoko Yamada, Yuki Omori, Shintaro Yano, Miyabi Ioka, Nahoko Kuwabara, Remi Nagano, Megumi Nozawa, Yumi Osawa, Hiroshi Maegawa, Shinji Kume, Shinichi Araki, Itsuko Miyazawa, Katsutaro Morino, Ikuko Kawai, Masumi Sobata, Motoko Takaoka, Yasushi Iwaita, Takashi Udagawa, Ami Inamori, Aya Kawase, Aya Yamanaka, Hitoshi Shimano, Akiko Fujita, Hitoshi Iwasaki, Hirayasu Kai, Yoshinori Osaki, Chie Saito, Motohiro Sekiya, Ryoya Tsunoda, Kunihiro Yamagata, Rikako Nakamura, Aiko Yamada, Mitsuru Ohsugi, Motoharu Awazawa, Ryotaro Bouchi, Shota Hashimoto, Makiko Hashimoto, Tomoko Hisatake, Noriko Ihana, Koko Ishizuka, Kazuo Izumi, Hiroshi Kajio, Michi Kobayashi, Noriko Kodani, Koji Maruyama, Michihiro Matsumoto, Maya Matsushita, Tomoka Nakamura, Takehiro Sugiyama, Akiyo Tanabe, Aiko Terakawa, Kojiro Ueki, Yuko Orimo, Takako Ozawa, Eriko Takahira, Yoshimitsu Yamasaki, Masakazu Haneda, Tadahiro Tomita, Saori Akimoto, Akihiro Fujimoto, Kenji Ishihara, Chiho Murakami, Akiyo Nishiyama, Yukiko Toyonaga, Kana Uozumi, Yukihiro Yamaji, Tetsuya Shigehara, Jun Okajyo, Yukihiro Shimizu, Shingo Iwasaki, Yuki Fukao, Megumi Furusho, Shintaro Nunokawa, Hideki Katagiri, Tomohito Izumi, Keizo Kaneko, Shinjiro Kodama, Mariko Miyazaki, Yuichiro Munakata, Tasuku Nagasawa, Yuji Oe, Hiroto Sugawara, Kei Takahashi, Kazushige Hirata, Keiko Inomata, Shoko Otomo, Taeko Uchida, Chigusa Yamashita, Arihiro Kiyosue, Ryota Tamura, Francois Dube, Marilene Bolduc, Marie-Christine Talbot, Leslie Cham, Vesta Lai, Josephine Tse, Shivinder Jolly, Tabbatha Duck, Scott Lyle, Rachel Epp, Camille Galloway, Susan Haskett, Elizabeta Matvienko, Liam Paulsen, Louise Moist, Zabrina Lozon, Tina Ramsey, Brittany Whitmore, Bader Al-Zeer, Paula Macleod, Aoife O'Sullivan, Zainab Sheriff, Sam Tholl, Amritanshu Pandey, Samantha Armstrong, Bethelihem Gebeyehu, Patrick Toth, Ronald Goldenberg, Mahsa Jahangiriesmaili, Shariff Sanguila, Neethi Suresh, Tanvi Talsania, Nadia Zalunardo, Mohsen Agharazii, Marie-Pier Roussel, Annie Saillant, France Samson, Harpreet Bajaj, Miken Bhavsar, Parul Dhall, Gagandeep Dhillon, Bhupinder Grewal, Taniya Nimbkar, Francois Madore, Guylaine Marcotte, Oren Steen, Mathura Bullen, Shayani Raguwaran, Andre Valleteau, Marie-France Langlois, Christine Brown, Andrew Steele, Melissa Garrity, Taneera Ghate, Holly Robinson, Michael Tolibas, Chetna Tailor, Lauren Elliott, Christine McClary-Wright, Fadia Boreky, Sameh Fikry, Ayesha Ali, Chintankumar Barot, Wagdy Basily, Thisun Saram, Vinay Varad, Hasnain Khandwala, Alex Aguilera, Patricia Alvarez, Balwinder Gill, Nazihah Huda, Aamir Navivala, Daniel Pinto, Micheli Bevilacqua, Elaine Fung, Geraldine Hernandez, Puneet Mann, Jaskiran Saini, Remi Rabasa-Lhoret, Danijela Bovan, Marie Devaux, Cecilia Barnini, Giovanna Leoncini, Luca Manco, Giulia Nobili, Matteo Piemontese, Filippo Aucella, Rachele Grifa, Francesco Totaro, Gaetano La Manna, Irene Capelli, Giuseppe Cianciolo, Sarah Lerario, Fulvia Zappulo, Alberto Rosati, Filippo Fani, Giuseppe Spatoliatore, Loreto Gesualdo, Francesco Pesce, Maria Russo, Maria Zippo, Cesira Cafiero, Daria Motta, Simona Bianco, Donatella Bilucaglia, Piergiorgio Messa, Laura Pavone, Federica Tripodi, Simone Vettoretti, Paola Fioretto, Gianni Carraro, Filippo Farnia, Anna Postal, Alessandro D'Amelio, Antonio Cardone, Giovanni Piccinni, Annalisa Aloisi, Francesco Scolari, Federico Alberici, Alice Guerini, Chiara Saccà, Chiara Salviani, Roberta Zani, Luca De Nicola, Carlo Garofalo, Maria Elena Liberti, Roberto Minutolo, Luigi Pennino, Lucio Polese, Paolo Mené, Simona Barberi, Clorinda Falcone, Francesco Russo, Maurizio Caroppo, Gennaro Santorelli, Rodolfo Rivera, Domenico Santoro, Alfio Giuffrida, Fortunata Zirino, Cristina Calvi, Luca Estienne, Giovanni Gambaro, Concetta Gangemi, Vittorio Ortalda, Giuseppina Pessolano, Giuseppe Grandaliano, Rocco Baccaro, Pietro Ferraro, Roberto Mangiacapra, Marco Melandri, Nadia Foligno, Rita Quartagno, Giuseppe Vezzoli, Elena Brioni, William G, Herrington, Natalie, Staplin, Christoph, Wanner, Jennifer B, Green, Sibylle J, Hauske, Jonathan R, Emberson, David, Prei, Parminder, Judge, Kaitlin J, Mayne, Sarah Y A, Ng, Emily, Sammon, Doreen, Zhu, Michael, Hill, Will, Steven, Karl, Wallendszu, Susanne, Brenner, Alfred K, Cheung, Zhi-Hong, Liu, Jing, Li, Lai Seong, Hooi, Wen, Liu, Takashi, Kadowaki, Masaomi, Nangaku, Adeera, Levin, David, Cherney, Aldo P, Maggioni, Roberto, Pontremoli, Rajat, Deo, Shinya, Goto, Xavier, Rossello, Katherine R, Tuttle, Dominik, Steubl, Michaela, Petrini, Dan, Massey, Jens, Eilbracht, Martina, Brueckmann, Martin J, Landray, Colin, Baigent, Richard, Hayne, EMPA-KIDNEY Collaborative Group: Colin Baigent, The, J Landray, Martin, Wanner, Christoph, G Herrington, William, Haynes, Richard, B Green, Jennifer, J Hauske, Sibylle, Brueckmann, Martina, Hopley, Mark, von-Eynatten, Maximillian, George, Jyothi, Brenner, Susanne, K Cheung, Alfred, Preiss, David, Liu, Zhi-Hong, Li, Jing, Hooi, Laiseong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Pontremoli, Roberto, P Maggioni, Aldo, Staplin, Natalie, Emberson, Jonathan, Hantel, Stefan, Goto, Shinya, Deo, Rajat, R Tuttle, Katherine, Hill, Michael, Judge, Parminder, J Mayne, Kaitlin, A Ng, Sarah Y, Rossello, Xavier, Sammons, Emily, Zhu, Doreen, Sandercock, Peter, Bilous, Rudolf, Herzog, Charle, Whelton, Paul, Wittes, Janet, Bennett, Derrick, Achiri, Patricia, Ambrose, Chrissie, Badin, Cristina, Barton, Jill, Brown, Richard, Burke, Andy, Butler, Sebastian, Dayanandan, Rejive, Donaldson, Pia, Dykas, Robert, Fletcher, Lucy, Frederick, Kate, Kingston, Hannah, Gray, Mo, Harding, Emily, Hashimoto, Akiko, Howie, Lyn, Hurley, Susan, Lee, Ryonfa, Luker, Nik, Murphy, Kevin, Nakahara, Mariko, Nolan, John, Nunn, Michelle, Mulligan, Sorcha, Omata, Akiko, Pickworth, Sandra, Qiao, Yanru, Shah, Shraddha, Taylor, Karen, Timadjer, Alison, Willett, Monique, Wincott, Liz, Yan, Qin, Yu, Hui, Bowman, Louise, Chen, Fang, Clarke, Robert, Goonasekera, Michelle, Karsan, Waseem, Mafham, Marion, Reith, Christina, Zayed, Mohammed, Ellison, Ritva, Moys, Rowan, Stevens, Will, Verdel, Kevin, Wallendszus, Karl, Bowler, Chri, Brewer, Anna, Measor, Andy, Cui, Guanguo, Daniels, Charle, Field, Angela, Goodenough, Bob, Lawson, Ashley, Mostefai, Youcef, Radhakrishnan, Dheeptha, Syed, Samee, Xia, Shuang, Adewuyi-Dalton, Ruth, Arnold, Thoma, Beneat, Anne-Marie, Bhatt, Anoushka, Bird, Chloe, Breach, Andrew, Brown, Laura, Caple, Mark, Chavagnon, Tatyana, Chung, Karen, Clark, Sarah, Condurache, Luminita, Eichstadt, Katarzyna, Espino Obrero, Marta, Forest, Scarlett, French, Helen, Goodwin, Nick, Gordon, Andrew, Gordon, Joanne, Guest, Cat, Harding, Tina, Hozak, Michal, Lacey, Matthew, Maclean, David, Messinger, Louise, Moffat, Stewart, Radley, Martin, Shenton, Claire, Tipper, Sarah, Tyler, Jon, Weaving, Lesley, Wheeler, Jame, Williams, Elissa, Williams, Tim, Woodhouse, Hamish, Chamberlain, Angela, Chambers, Jo, Davies, Joanne, Donaldson, Denise, Faria-Shayler, Pati, Fleming-Brown, Denise, Ingell, Jennifer, Knott, Carol, Liew, Anna, Lochhead, Helen, Meek, Juliette, Rodriguez-Bachiller, Isabel, Wilson, Andrea, Zettergren, Patrick, Aitsadi, Rach, Barton, Ian, Baxter, Alex, Bu, Yonghong, Danel, Lukasz, Grotjahn, Sonja, Kurien, Rijo, Lay, Michael, Maskill, Archie, Murawska, Aleksandra, Raff, Rachel, Young, Allen, Sardell, Rebecca, Cejka, Vladimir, Fajardo-Moser, Marcela, Hartner, Christian, Poehler, Dori, Renner, Janina, Scheidemantel, Franziska, Bryant, Miya, Hepditch, Anita, Johnson, Cassandra, Latore, Erin, Miller, Yolanda, Price, Lauren, Whalen, Merilee, Wheeler, Ashleigh, Ingell, Jenny, An, Yu, Chen, Yinghua, Chen, Peiling, Dai, Hao, Du, Hong, Feng, Fang, Guo, Qing, Hou, Libo, Hundei, Wuhanbilige, Jin, Binbin, Li, Yan, Liu, Jiamin, Song, Xia, Wang, Yanping, Yu, Yanwu, Zhang, Ning, Zhao, Lingshan, Zhong, Hui, Beng Goh, Cheng, Mun Low, Ye, Yi Sor, Soon, Hanis Zulkipli, Farah, Sivanandam, Sarojini, Arai, Natsuki, Fukasawa, Ai, Furukawa, Mizue, Habuki, Keisuke, Hayashi, Shoko, Isari, Wakako, Kanegae, Saki, Kawai, Maria, Kobayashi, Reiki, Kuramae, Takako, Kuribayashi, Chika, Maeno, Sawako, Masumoto, Satoshi, Morisaki, Tomoko, Oda, Minoru, Sawada, Kazue, Sugamori, Kenta, Tatsuzawa, Ayana, Tomita, Aiko, Yuasa, Kazuyuki, Inazawa, Hiroko, Axler, Amanda, Gallo, Kerri, Baldini, Ester, Bartolomei Mecatti, Barbara, Bianchini, Francesca, Ceseri, Martina, Cipressa, Laura, Fabbri, Gianna, Lorimer, Andrea, Lucci, Donata, Ghavampour, Sharang, Knoppe, Anja, Schmidt-Gurtler, Han, Dumann, Hubert, Merscher, Sybille, Patecki, Margret, Rainer Schlieper, Georg, Torp, Anke, Weber, Bianca, Zietz, Maja, Hohenstein, Bernd, Benck, Ur, Draganova, Diliana, Weinreich, Thoma, Wolf, Lothar, Gaidu, Jasmine, Reiner, Hanna, Visnjic, Mandy, Steffl, Daniel, Breitenfeldt, Marie, Kraemer-Guth, Annette, Braun, Christine, Hagge, Simone, Schomig, Michael, Matthias, Stephan, Stoffler, Dominik, Schumacher, Beate, Sitter, Thoma, Fuessl, Louise, Krappe, Julia, Loutan, Jerome, Vielhauer, Volker, Andriaccio, Luciano, Maurer, Magdalena, Winkelmann, Bernhard, Dursch, Martin, Seifert, Linda, Tenbusch, Linda, Weinmann-Menke, Julia, Boedecker, Simone, Kaluza-Schilling, Wiebke, Kraus, Daniel, Krieger, Carina, Schmude, Margit, Schreiber, Anne, Eckrich, Ewelina, Tschope, Diethelm, Arbi, Abdulwahab, Lee-Barkey, Young, Stratmann, Bernd, Prib, Natalie, Rolfsmeier, Sina, Schneider, Irina, Rump, Lar, Stegbauer, Johanne, Pötz, Christine, Schemmelmann, Mara, Schmidt, Claudia, Koch, Michael, Aker, Sendogan, Küpper, Annika, Martin, Manuela, Pfab, Thiemo, Albert, Christian, Haase, Michael, Zander, Barbara, Schneider-Danwitz, Claudia, Seeger, Wolfgang, Seeger, Wolf-Adam, Zemann, Britta, Stellbrink, Christoph, Marx, Kristin, Stellbrink, Ekaterina, Brettschneider, Britta, Watson, Stephanie, Iselt, Marion, Klausmann, Gerhard, Kummer, Inga-Nadine, Kutschat, Auguste, Streitenberger, Simone, Girndt, Matthia, Markau, Silke, Girakossyan, Ina, Hanf, Claudia, Beige, Joachim, Wendt, Ralph, Schmidt, Ulrike, Schneider, Andrea, Veelken, Roland, Donhauser, Claudia, Becker, Lui, Miftari, Nexhat, Wolfling, Ricarda, Morlok, Sarah, Hugo, Christian, Paliege, Alexander, Passauer, Jen, Stumpf, Julian, Fleischer, Annegret, Haaser, Kerstin, Kraemer, Bernhard, Jochims, Jan, Kruger, Bernd, Foellinger, Claudia, Reisler, Anastassiya, Strutz, Frank, Haack, Stefan, Hohenstatt, Ursula, Busch, Martin, Herfurth, Konstantin, Wolf, Gunter, Paul, Rainer, Haller, Hermann, Kaufeld, Jessica, Menne, Jan, Bahlmann-Kroll, Elisabeth, Bergner, Angela, Weihprecht, Horst, Er, Aydin, Sonntag, Florian, Turan, Elif, Wittmann, Michael, Klauser, Franziska, Voigt, Eva, Schettler, Volker, Schulz, Egbert, Rohnstock, Madlen, Schettler, Elke, Schroppel, Bernd, van Erp, Rene, Kachele, Martin, Ludwig, Ulla, Schulte-Kemna, Lena, Kmietschak, Waltraud, Preiss, Elke, Ruocco, Martina, Heine, Gunnar, Brzoska, Martin, Gabel, Sebastian, Büttner, Christina, Sabarai, Asma, Banas, Bernhard, Bergler, Tobia, Ehrl, Yvonne, Putz, Franz, Schuster, Antonia, Kuhn, Stefanie, Schramm, Torsten, Degenhardt, Stefan, Schmidt, Gerhard, Weiland, Lea, Giebeln-Hudnell, Ulrike, Kielstein, Jan, Eden, Gabriele, Fuchs, Brigitte, Morig, Gina, Winkler, Manuela, Darius, Harald, Kriatselis, Charalampo, Roesch, Carl-Philipp, Maselli, Astrid, Alscher, Dominik, Ketteler, Marku, Schanz, Moritz, Schricker, Severin, Rettenmaier, Bianka, Schwab, Andrea, Pergola, Pablo, Leal, Irene, Cagle, Melissa, Romo, Anna, Torres, Anthony, Joshi, Sucharit, Barrett, Kulli, Africano, Alexi, Dodds, Vicki, Gowen, Dorleena, Morris, Ashlee, Fernandez, Juan, Jimenez, Guillermo, Viera, Ricardo, Bruce, Kendaling, Barrios, Ryan, Garcia, Maylin, Garcia, Kerelyn, Leal, Iradi, Tietjen, David, Bains, David, Castillo, Carlo, Brewer, Genielle, Davis, Justin, Freking, Natalie, Golson, Brittany, Ham, Sally, Roesch, Jesslyn, Suchinda, Pusadee, Beigh, Shameem, Lilavivat, Usah, Bilton, Joyce, Bocchicchia, Kim, Turner, Jeffrey, Dahl, Neera, Peixoto, Aldo, Kavak, Yasemin, Liberti, Lauren, Nair, Hari, Page, Nicola, Rosenberg, Stephanie, Simmons, Kathryn, Isakova, Tamara, Frazier, Rebecca, Mehta, Rupal, Srivastava, Anand, Fox, Patrick, Hecktman, Jonathan, Hodakowski, Alexander, Martinez, Carlo, Phillips, Rachel, Stevenson, Alexi, Mustafa, Reem, Jansson, Kyle, Kimber, Cassandra, Stubbs, Jason, Tuffaha, Ahmad, Yarlagadda, Sri, Griffin, Debbie, Laundy, Elisabeth, Tang, Zhuo, Alicic, Radica, Cooper, Ann, Davis, Lisa, Gore, Ashwini, Goldfaden, Rebecca, Harvill, Leslie, Hichkad, Lisa, Johns, Barry, Jones, Thoma, Merritt, Kayla, Sheldon, Jennifer, Stanfield, Jennifer, Alexander, Lindsay, Preston, Kaitlyn, Wood, Lindsey, Pradhan, Rajesh, Deraad, Roger, Mcintosh, Kelli, Raymond, Loui, Shepperd, Michael, Mclaughlin, Susan, Seifert, Mary, Shepherd, Andrew, Aiello, Joseph, Durham, William, Loudermilk, Laurie, Manley, John, Burnette, Sabrina, Evans, Stephanie, Johnson, Tara, Sloan, Lance, Ann Acosta, Judy, Gillham, Stacy, Sloan, Katia, Squyres, Sueann, Rocco, Michael, Hawfield, Amret, Bagwell, Ben, Richmond, Lauren, Soufer, Joseph, Clarke, Subha, Aliu, Amanda, Calabrese, Kristine, Davis, Amanda, Poma, Veronica, Spinola, Tracy, Magee, Jame, Silva, Ricardo, Choksi, Rushab, Dajani, Lorraine, Evans, John, George, Anil, Krish, Prasanth, Martins, Gerard, Sheikh-Ali, Mae, Sutton, David, Driver, Freda, Hanburry, Abraham, Hume, Laura, Hurst, Amber, Taddeo, Matthew, Turner, Marla, Yousif, Veronica, Beddhu, Srinivasan, Al-Rabadi, Laith, Abraham, Nikita, Caamano, Amalia, Carle, Judy, Gonce, Victoria, Staylor, Kaitlyn, Zhou, Na, Bansal, Shweta, Bhattarai, Manoj, Sharma, Kumar, Debnath, Subrata, Garza, Aliseiya, Velagapudi, Chakradhar, Rovner, Sergio, Almeida, Javier, Casares, Pablo, Stewart-Ray, Verlaine, Almaraz, Rene, Dayrell, Renata, Moncada, Ana, Pulido, Ricardo, Rodriquez, Roxana, Deeb, Wasim, Degoursey, Kathryn, Gloria, Rodel, Greene, Trevor, Miller, Robert, Pereira, Edward, Roura, Miguel, Domingo, Debbie, Dorestin, Sasha, Hodge, William, Jackson, Cathy, Lund, Deborah, Taylor, Katrina, Boren, Kenneth, Cleveland, Brittany, Gaiser, Sandra, Sahani, Mandeep, Aldrich, Logan, Edmerson, Exodu, Limon, Edmond, Valletta, Cole, Vasquez, Patricia, Provenzano, Christopher, Brar, Navkiranjot, Henderson, Heather, Keith, Bellovich, Khai, Qur, Khairullah, Quresh, Makos, Gail, Topf, Joel, Gasko, Sherry, Henschel, Rosemarie, Knapp, Kaitlin, Kozlowski, Teresa, Lafleur, Paula, Varughese, Ashwathy, Xue, Hui, Wu, Patricia, Arechiga, Olga, Darbeau, Shan, Fechter, Michael, Martinez, Stephanie, Hanson, Lenita, Cooper, Nyla, Madera, Areli, Cadorna, Jay, Sheridan, Rita, Sparks, Helen, Eilerman, Bradley, Bodine, Susanne, Eid, Wael, Flora, Rebecca, Avery, Amber, Hardy, Cashmere, Biscoveanu, Mihaela, Nagelberg, Steven, Cummins, Tracey, Rahbari-Oskoui, Frederic, Oommen, Anju, Forghani, Zohreh, Hitchcock, Stacie, Hosein, Darya, Watkins, Diane, Patel, Minesh, Lambert, Anthony, Newman, Elizabeth, Wood, Autumn, Ross, Tammy, Topping, Stephany, Mulhern, Jeffrey, Murphy, Lorna, Vasseur, Ann, Greenwood, Gregory, Hadley, Alexander, Laurienti, Denise, Marshall, Christopher, Mclean, Nichola, Satko, Scott, Caudill, Brandy, Maris, Jacob, Rogers, Janice, Vanhoy, Cindy, Thomas, George, Nakhoul, George, O'Toole, John, Taliercio, Jonathan, Cooperman, Leslie, Markovic, Marina, Tucky, Barbara, Dev, Devasmita, Hasan, Alia, Yalamanchili, Hima, Jain, Namita, Mcneil, Lesley, Wines, Eric, Park, Jean, Ghazi, Adline, Hamm, Mia, Patel, Teja, Mottl, Amy, Chang, Emily, Derebail, Vimal, Cole, Emmie, Froment, Anne, Kelley, Sara, Osmond Foster, Jordan, Mahabadi, Vahid, Jafari, Golriz, Kamarzarian, Anita, Arriaga, Wendy, Arteaga, Daisy, Machicado, Rosario, Naverrete, Genesi, Kumar, Prashant, Nazeer, Imran, Urquia, Karina, Glider, Tammi, Jones, Vickie, Rucker, Savannah, Wiley, Jennifer, Pandey, Rahul, Arroyo, Jesu, Pariani, Harish, Ahmad, Mohammad, Mozaffari, Shahin, Perez, Erika, Budoff, Matthew, Roy, Sion, Birudaraju, Divya, Ghanem, Ahmed, Hamal, Sajad, Aronoff, Stephen, Joye Petr, Elisa, Sachson, Richard, Wiebel, Jaime, Akram, Sana, Jones, Laurie, Knight, Curti, Tarlac, Maurie, Ahmed, Shahbaz, Szerlip, Harold, Akinfolarin, Akinwande, Mehta, Ankit, Camp, Shana, Castro, Cindy, Cooper, Zanaida, Terry, Jessica, Awad, Ahmed, Kothapalli, Bhavya, Lustig, Ryan, Alfaress, Serine, Jasim, Hyder, Parrigon, Mary, Karounos, Denni, Ahmed, Sadiq, Berry, Maggie, Oremus, Ruth, Hernandez-Cassis, Carlo, Ugwu, Elia, Junejo, Nazia, Suazo, Nancy, Segal, Mark, Kazory, Amir, Brown, Sherry, Daniels, Tristan, Dayi, Sofia, Hogan, Renee, Mccray, Kathy, Stickley, Jennifer, Rahman, Mahboob, Dobre, Mirela, Negrea, Lavinia, Padiyar, Aparna, Pradhan, Nishigandha, Rashidi, Arash, Sarabu, Nagaraju, Donley, Vicki, Young, Tricia, Oguchi, Godson, Onyema, Judepatrick, Damianik, Kahla, Dienes, Jack, Plummer-Morgan, Judith, Roman, Marilyn, Skipper, Mauver, Villaruel, Stacey-Ann, Williams, Krystle, Sugimoto, Danny, Dugas, Jeffrey, Ahmed, Ismeal, Bhairoo, Jamie, Rijos, Dolore, Salim, Huzaifa, Gavrila, Madita, Lafferty, Kathryn, Rabara, Ria, Ruse, Sally, Weetman, Maria, Bushnell, Jame, Power, Albert, Jenkins, Alison, Jones, Stefanie, Scott, Amanda, Byrne, Cath, Jesky, Mark, Cowley, Alison, Mchaffie, Emma, Waterfall, Holly, Taylor, Jo, Bough, Laura, Phillips, Thoma, Winter-Goodwin, Barbara, Phin Kon, Sui, Macdougall, Iain, Lioudaki, Eirini, Shah, Sapna, Sharpe, Claire, Aguilar, Francisco, Hernandez Pena, Abegail, Pugay, Conception, Te, Amelia, Finn, Hugh, Hanif, Wasim, Mostafa, Samiul, Aitken, Alice, Draxlbauer, Katharine, Grobovaite, Evelina, Kearney, Jennifer, Mccarthy, Theresa, Gentile, Giorgio, Browne, Duncan, Chellamuthu, Palanichamy, Dugal, Tabinda, Chant, Terri, Jones, Laura, Laity, Emily, Miners, Megan, Muir, Jame, Swanson, Elizabeth, Frankel, Andrew, Tomlinson, Jame, Alegata, Marlon, Almasarwah, Rashid, Apostolidi, Anthoula, Vourvou, Maria, Walters, Thoma, Taal, Maarten, Dukka, Hari, Kolhe, Nitin, Mcdonald, Carly, White, Kelly, Ugni, Shiva, Gunda, Smita, Oluyombo, Rotimi, Brindle, Vicki, Coutts, Ping, Fuller, Tracy, Nadar, Evelyn, Ramadoss, Suresh, Motherwell, Nichola, Pajak, Susannah, Tonks, Louise, Bhandari, Sunil, Bodington, Richard, Hazara, Adil, Fellowes, Dominic, Wong, Christopher, Goldsmith, Christopher, Barnes, Sherald, Bennett, Ann, Burston, Claire, Hope, Samantha, Hunt, Nicola, Kurian, Lini, Fish, Richard, Farrugia, Daniela, Lee, Judy, Sadler, Emma, Turner, Hannah, Hill, Christopher, Brown, Henry, Masengu, Agne, Maxwell, Peter, Bleakley, Nina, Murtagh, Hugh, Petchey, William, Yiu, Vivian, Kellett, Joanne, Williams, Angharad, Clarke, Helen, Carnall, Victoria, Benyon, Sarah, Blake, Caroline, Estcourt, Stephanie, Piper, Jane, Morgan, Neal, Hutchinson, Carolyn, Mckinley, Teresa, Woodman, Alastair, Graham, Judi, Leonard, Niall, Smyth, John, Adell, Vicki, Hagan, Samantha, Caplin, Ben, Oomatia, Amin, Damian, Eleanor, Sobande, Toluleyi, Doulton, Tim, Delaney, Michael, Montasser, Mahmoud, Hansen, Jenny, Loader, David, Moon, Angela, Morris, France, Sinha, Smeeta, Chukwu, Chukwuma, Hudson, Amy, Campbell, Diane, Kershaw, Melanie, Whittaker, Stephanie, Irtiza-Ali, Ayesha, Ghalli, Farid, Nosseir, Heba, Leslie, Allison, Trivedi, Kate, Fraser, Donald, Alhadj Ali, Mohammad, Griffin, Sian, Latif, Farah, Witczak, Justyna, Wonnacott, Alexa, Jeffers, Lynda, Webley, Yvette, Phelan, Paul, Miller-Hodges, Eve, Geddes, Ailsa, Glenwright, Margaret, Hunter, Amy, Pickett, Thoma, Moriarty, Jim, Hill, Linda, Tyler, Amanda, Ayub, Waqar, Evans, Gail, Hewins, Sue, Hewitt, Davina, Read, Kerry, Bell, Samira, Cosgrove, Leanne, Craik, Rachel, Murray, Shona, Bhandary, Nitin, Coles, Holly, Easow, Rashmi, Joseph, Maya, Khwaja, Arif, Jackson, Yvonne, Mbuyisa, Angeline, Sellars, Rachel, Chitalia, Nihil, Mohandas, Cynthia, Gherman, Anca, Kamundi, Charlotte, Olufuwa, Olumide, Mccafferty, Kieran, Adeleke, Adedolapo, Healy, Cara, Jeyarajah, Damini, Kinsella-Perks, Edward, Smith, Richard, Camilleri, Brian, Buckman, Carol, Finch, Jenny, Rivers, Vanessa, Connor, Andrew, Carr, Sheila, Shainberg, Lisa, Lewington, Andrew, Baker, Richard, Dorey, Suzannah, Tobin, Kay, Wheatley, Rosalyn, Banerjee, Debasish, Hull, Richard, Abat, Sharirose, Paul, Riny, Karim, Mahzuz, Htet, Zay, Tufail, Saad, Varma, Ravi, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Tropman, Emily, Abdul-Samad, Thahir, Grace, Anne, Phipps, Marie, Suckling, Rebecca, Somalanka, Subash, Sood, Bhrigu, Swift, Pauline, Acheampong, Sarah, Ansu, Kwame, Augustin, Martia, Sampson, Anna, Vinall, Lynn, Wren, Kim, Wanninayake, Shamila, Wooding, Nichola, Edwards, Heather, Owen, Lydia, Bolton, Stephanie, Carson, Marion, Matthews, Michael, Brunskill, Nigel, Jesus-Silva, Jorge, Howson, Alex, Quashie-Akponeware, Mary, Tindall, Hilary, Nethaji, Chidambaram, Eldon, Helen, Patel, Rajan, Mark, Patrick, Rankin, Alastair, Sullivan, Michael, Forsyth, Kirsty, Mcdougall, Rowan, Dasgupta, Tanaji, Davies, Louisa, Ryder, Maggie, Grimmer, Philip, Macdonald, Clare, Webster, Mary, Newcastle, Newcastle, Ellam, Timothy, Wong, Edwin, Meshykhi, Christine, Webster, Andrea, Wilson, Peter, Vilar, Enric, Berdeprado, Jocelyn, Doctolero, Eunice, Wilkinson, Lily, Mccarroll, Frank, Ammar, Hesham, Kuan, Ying, Moran, Conor, Shivashankar, Girish, Campbell, Ryan, Glowski, Deborah, Mcdermott, Paula, Ali, Amar, Patel, Zuber, Bond, Christine, Whalley, Gillian, Zhang, Haitao, Yang, Liu, Zhang, Lihua, Kan, Tingting, Zhu, Ling, Zhao, Jinghong, Hou, Weiping, Wu, Jing, Cheng, Hong, Bian, Weijing, Zhao, Zhirui, Shao, Fengmin, Cao, Huixia, Jiao, Xiaojing, Niu, Peiyuan, Niu, Jianying, Chen, Yu, Zhang, Lihong, Zhu, Shenglang, Lin, Haiyan, Yao, Shaopeng, Chen, Jiehui, Jiang, Ying, Hu, Ying, Xiao, Huaying, Yang, Fuye, Zhang, Xinzhou, Guo, Baochun, Jin, Qiu, Liu, Lixia, Xiao, Xiangcheng, Xie, Yanyun, Meng, Ting, Xu, Chuanwen, Huang, Jie, Xu, Yanmei, Kong, Weixin, Wang, Xiaoliang, Liu, Qianpan, Wang, Xueying, Gao, Ming, Hu, Xiumei, Lu, Ying, Wang, Li, Peng, Kun, Wang, Wei, Gong, Qiuhong, Cai, Jianfang, Li, Xiaojue, Liu, Xuejiao, Zhou, Shuhan, Liu, Hong, Weng, Yao, Tang, Shuai, Yao, Yao, Zhao, Shi, Cheng, Chen, Wei, Wei, Li, Na, Aqashiah Mazlan, Sadanah, Zubaidah Bahtar, Alia, Katiman, Elliyyin, Othman, Noraini, Mushahar, Lily, Mazlan, Nurdiana, Sharafina Safiee, Nur, Ramasamy, Sarasa, Seng Wong, Hin, Ahmad Rosdi, Hajar, Zhao Zhi Tan, Esther, Fan Tay, Ju, Seng Teng, Kok, Yahaya, Hasnah, Jiun Liu, Wen, Wee Ee, Lik, Kay Leong Khoo, Kenneth, Mohd Yusoff, Yuana, Safhan Mohamad Nor, Fariz, Kamil Ahmad, Mohd, Ramli Seman, Mohd, Hui Hong Tan, Clare, Lui Sian Ngu, Laura, Yoke May Chan, Jaime, Peji, Javelin, Loong Loh, Chek, Yan Lee, Yee, Ramanaidu, Sridhar, Mean Thong, Kah, Hong Wong, Yik, Junus, Suria, Hua Ching, Chen, Faisal Asmee, Mohammad, Ruziana Ku Md Razi, Ku, Leong Low, Chun, Sze Bing Sim, Christopher, Duan Tham, Zhang, Kamila Abdullah, Noor, Meng Chen, Tai, Chieh Chan, Yong, Chang, Eason, Yean Kang, Huan, Quan Lee, Kai, Ann Lee, Sue, Kheng Lee, Aik, Vinathan, Jeevika, Abdul Cader, Rizna, Mustafar, Ruslinda, Kamaruzaman, Lydia, Mohd, Rozita, Ismail, Rahimah, Men Leong, Chong, Koon Low, Chee, Wei Wong, Liang, Adnan, Norlezah, Ibrahim, Sabariah, Zaimi Abdul Wahab, Mohamad, Bavanandan, Sunita, Shen Lim, Yik, Hazlina Wan Mohamad, Wan, Munirah Jaafar, Siti, Ashykeen Mohd Fauzi, Nur, Sudin, Aziee, Kun Lim, Soo, Chung Gan, Chye, Hing, Albert, Ahmad Faizal Alaidin Razali, Wan, Fong Liew, Yew, Bao Tyng Chan, Chelsia, Chih Cheng, Mei, Chen Ong, Yu, Meng Ong, Loke, Amalina Mohamed Affandi, Farah, Rahmat, Korina, Chai Peng, Ban, Amat, Masayu, Hadafi Ahmad, Nuzaimin, Yee Mah, Doo, Loon Tye, Yi, Azhari, Zaid, Nabilah Mohamad Zaini, Siti, Aidil Musa, Mohd, Ahmad Miswan, Norazinizah, Ramli, Rafizanur, Aziah Ahmad, Nor, Leong Goh, Bak, Izah Ahmad, Nurul, Huda Ibrahim, Fairol, Jian Ng, Tze, Shanmuganathan, Malini, Lian Tay, Li, Harun, Zaiha, Ramli, Salmi, 'Ain Yusof, Nurul, Abd Rahman, Rossenizal, Iqbal Abdul Hafidz, Muhammad, Hidayati Mohd Sharif, Nur, Yasmoon Awang, Irda, Nakashima, Eitaro, Imamine, Rui, Minatoguchi, Makiko, Miura, Yukari, Nakaoka, Miduki, Suzuki, Yoshiki, Yoshikawa, Hitomi, Shin, Koki, Fujita, Kanae, Iwasa, Misuzu, Sasajima, Haruka, Sato, Airi, Hamamoto, Yoshiyuki, Fujita, Yuki, Haraguchi, Takuya, Hyo, Takanori, Izumi, Kiyohiro, Komiya, Toshiyuki, Kubota, Sodai, Kurose, Takeshi, Kuwata, Hitoshi, Nakatani, Susumu, Oishi, Kaori, Okamoto, Saki, Okamura, Kaori, Takeoka, Jun, Tanaka, Nagaaki, Tanigaki, Katsuya, Toda, Naohiro, Watanabe, Koin, Komori, Hiromi, Kumuji, Rika, Takesada, Asako, Tanaka, Aya, Maruyama, Shoichi, Hasegawa, Tomonori, Ishiguro, Akiko, Ishimoto, Takuji, Ito, Kazuhiro, Kamimura, Yutaka, Kato, Noritoshi, Kato, Sawako, Kojima, Hiroshi, Kosugi, Tomoki, Maeda, Kayaho, Mizuno, Masasi, Saito, Shoji, Sato, Hitomi, Sato, Yuka, Suzuki, Yasuhiro, Tanaka, Akihito, Yasuda, Yoshinari, Hasegawa, Fujiko, Hayashi, Maiko, Higashi, Shizuka, Shimamura, Kaho, Sumi, Momoko, Tajima, Kazuki, Unekawa, Chimaki, Wakayama, Kana, Wakita, Yukiko, Otani, Takatoshi, Imai, Ayako, Kawashima, Sayaka, Kogure, Eri, Sato, Tomoe, Takezawa, Misato, Yoshida, Shinya, Araki, Hideo, Katsuda, Yuko, Konishi, Masahiro, Matsunaga, Takahiro, Oe, Masashi, Ogane, Kunihiro, Sakai, Masato, Takahashi, Tomoko, Yamano, Takahiro, Yokoyama, Takuya, Ito, Hitomi, Katayama, Masayo, Kuroda, Emi, Ikeda, Toru, Kojo, Takuma, Yoshidome, Etsuo, Mizumachi, Rieko, Yamamoto, Akane, Yamasaki, Narihisa, Yamasaki, Yoshihiko, Wada, Jun, Eguchi, Jun, Higuchi, Chigusa, Katayama, Akihiro, Kinomura, Masaru, Kitagawa, Masashi, Kitamura, Shinji, Miyamoto, Satoshi, Morinaga, Hiroshi, Nakatsuka, Atsuko, Nojima, Ichiro, Shikata, Kenichi, Sugiyama, Hitoshi, Tanabe, Katsuyuki, Tsuji, Kenji, Uchida, Haruhito, Watanabe, Mayu, Hashimoto, Chie, Kato, Takahiro, Yamamoto, Sayaka, Wada, Takehiko, Fukagawa, Masafumi, Hamano, Naoto, Koizumi, Masahiro, Komaba, Hirotaka, Nakagawa, Yosuke, Iwamoto, Michiyo, Masutani, Kosuke, Katanosaka, Akane, Kiyota, Mayu, Uchi, Hikari, Ueda, Yuka, Yamamoto, Sonoka, Nagasu, Hajime, Itano, Seiji, Iwakura, Tsukasa, Kadoya, Hiroyuki, Kanda, Eiichiro, Kashihara, Naoki, Kidokoro, Kengo, Kondo, Megumi, Sasaki, Tamaki, Satoh, Minoru, Tokuyama, Atsuyuki, Umeno, Reina, Wada, Yoshihisa, Yamamoto, Toshiya, Yamanouchi, Yu, Abe, Masumi, Inukai, Yoko, Ogawa, Wataru, Asahara, Shunichiro, Fujii, Hideki, Goto, Shunsuke, Hirota, Yushi, Hosooka, Tetsuya, Kono, Keiji, Nishi, Shinichi, Okada, Yuko, Sakaguchi, Kazuhiko, Sugawara, Kenji, Takahashi, Michiko, Takai, Tomoko, Tamori, Yoshikazu, Watanabe, Kentaro, Kitajima, Miyu, Nishi, Misaki, Wada, Junko, Ito, Yasuhiko, Kamiya, Hideki, Asai, Akimasa, Asai, Nao, Asano, Saeko, Banno, Shogo, Ejima, Yohei, Hase, Hanako, Hayami, Tomohide, Himeno, Tatsuhito, Ishikawa, Takahiro, Ito, Mayumi, Iwagaitsu, Shiho, Kasagi, Rina, Kato, Yoshiro, Kato, Makoto, Kato, Koichi, Katsuno, Takayuki, Kawai, Miyuka, Kinashi, Hiroshi, Kondo, Masaki, Koshino, Masako, Matsuoka, Naoya, Morishita, Yoshiaki, Motegi, Mikio, Nakamura, Jiro, Shimoda, Hiromi, Sugiyama, Hirokazu, Tsunekawa, Shin, Yamaguchi, Makoto, Takahashi, Kazuyo, Watada, Hirotaka, Funayama, Takashi, Furukawa, Yasuhiko, Gohda, Tomohito, Goto, Hiromasa, Kaga, Hideyoshi, Kanaguchi, Yasuhiko, Kanazawa, Akio, Kaneko, Kayo, Kano, Toshiki, Kihara, Masao, Kimura, Shogo, Kobayashi, Takashi, Maiguma, Masayuki, Makita, Yuko, Mano, Satoshi, Mita, Tomoya, Miyatsuka, Takeshi, Murakoshi, Maki, Muto, Masahiro, Nakata, Masami, Nakata, Junichiro, Nishida, Yuya, Nohara, Nao, Ogihara, Takeshi, Sato, Daisuke, Sato, Junko, Sato, Hiroaki, Suzuki, Yusuke, Suzuki, Ruka, Suzuki, Hitoshi, Takagi, Miyuki, Tamura, Yoshifumi, Uchida, Toyoyoshi, Ueda, Seiji, Asawa, Miki, Miyaji, Minako, Nagashima, Eri, Shibata, Yoshie, Yanagisawa, Eri, Yamauchi, Toshimasa, Hirakawa, Yosuke, Nishi, Hiroshi, Shojima, Nobuhiro, Horikawa, Satoko, Nakayama, Yukiko, Yamada, Naoko, Omori, Yuki, Yano, Shintaro, Ioka, Miyabi, Kuwabara, Nahoko, Nagano, Remi, Nozawa, Megumi, Osawa, Yumi, Maegawa, Hiroshi, Kume, Shinji, Araki, Shinichi, Miyazawa, Itsuko, Morino, Katsutaro, Kawai, Ikuko, Sobata, Masumi, Takaoka, Motoko, Iwaita, Yasushi, Udagawa, Takashi, Inamori, Ami, Kawase, Aya, Yamanaka, Aya, Shimano, Hitoshi, Fujita, Akiko, Iwasaki, Hitoshi, Kai, Hirayasu, Osaki, Yoshinori, Saito, Chie, Sekiya, Motohiro, Tsunoda, Ryoya, Yamagata, Kunihiro, Nakamura, Rikako, Yamada, Aiko, Ohsugi, Mitsuru, Awazawa, Motoharu, Bouchi, Ryotaro, Hashimoto, Shota, Hashimoto, Makiko, Hisatake, Tomoko, Ihana, Noriko, Ishizuka, Koko, Izumi, Kazuo, Kajio, Hiroshi, Kobayashi, Michi, Kodani, Noriko, Maruyama, Koji, Matsumoto, Michihiro, Matsushita, Maya, Nakamura, Tomoka, Sugiyama, Takehiro, Tanabe, Akiyo, Terakawa, Aiko, Ueki, Kojiro, Orimo, Yuko, Ozawa, Takako, Takahira, Eriko, Yamasaki, Yoshimitsu, Haneda, Masakazu, Tomita, Tadahiro, Akimoto, Saori, Fujimoto, Akihiro, Ishihara, Kenji, Murakami, Chiho, Nishiyama, Akiyo, Toyonaga, Yukiko, Uozumi, Kana, Yamaji, Yukihiro, Shigehara, Tetsuya, Okajyo, Jun, Shimizu, Yukihiro, Iwasaki, Shingo, Fukao, Yuki, Furusho, Megumi, Nunokawa, Shintaro, Katagiri, Hideki, Izumi, Tomohito, Kaneko, Keizo, Kodama, Shinjiro, Miyazaki, Mariko, Munakata, Yuichiro, Nagasawa, Tasuku, Oe, Yuji, Sugawara, Hiroto, Takahashi, Kei, Hirata, Kazushige, Inomata, Keiko, Otomo, Shoko, Uchida, Taeko, Yamashita, Chigusa, Kiyosue, Arihiro, Tamura, Ryota, Dube, Francoi, Bolduc, Marilene, Talbot, Marie-Christine, Cham, Leslie, Lai, Vesta, Tse, Josephine, Jolly, Shivinder, Duck, Tabbatha, Lyle, Scott, Epp, Rachel, Galloway, Camille, Haskett, Susan, Matvienko, Elizabeta, Paulsen, Liam, Moist, Louise, Lozon, Zabrina, Ramsey, Tina, Whitmore, Brittany, Al-Zeer, Bader, Macleod, Paula, O'Sullivan, Aoife, Sheriff, Zainab, Tholl, Sam, Pandey, Amritanshu, Armstrong, Samantha, Gebeyehu, Bethelihem, Toth, Patrick, Goldenberg, Ronald, Jahangiriesmaili, Mahsa, Sanguila, Shariff, Suresh, Neethi, Talsania, Tanvi, Zalunardo, Nadia, Agharazii, Mohsen, Roussel, Marie-Pier, Saillant, Annie, Samson, France, Bajaj, Harpreet, Bhavsar, Miken, Dhall, Parul, Dhillon, Gagandeep, Grewal, Bhupinder, Nimbkar, Taniya, Madore, Francoi, Marcotte, Guylaine, Steen, Oren, Bullen, Mathura, Raguwaran, Shayani, Valleteau, Andre, Langlois, Marie-France, Brown, Christine, Steele, Andrew, Garrity, Melissa, Ghate, Taneera, Robinson, Holly, Tolibas, Michael, Tailor, Chetna, Elliott, Lauren, McClary-Wright, Christine, Boreky, Fadia, Fikry, Sameh, Ali, Ayesha, Barot, Chintankumar, Basily, Wagdy, Saram, Thisun, Varad, Vinay, Khandwala, Hasnain, Aguilera, Alex, Alvarez, Patricia, Gill, Balwinder, Huda, Nazihah, Navivala, Aamir, Pinto, Daniel, Bevilacqua, Micheli, Fung, Elaine, Hernandez, Geraldine, Mann, Puneet, Saini, Jaskiran, Rabasa-Lhoret, Remi, Bovan, Danijela, Devaux, Marie, Barnini, Cecilia, Leoncini, Giovanna, Manco, Luca, Nobili, Giulia, Piemontese, Matteo, Aucella, Filippo, Grifa, Rachele, Totaro, Francesco, La Manna, Gaetano, Capelli, Irene, Cianciolo, Giuseppe, Lerario, Sarah, Zappulo, Fulvia, Rosati, Alberto, Fani, Filippo, Spatoliatore, Giuseppe, Gesualdo, Loreto, Pesce, Francesco, Russo, Maria, Zippo, Maria, Cafiero, Cesira, Motta, Daria, Bianco, Simona, Bilucaglia, Donatella, Messa, Piergiorgio, Pavone, Laura, Tripodi, Federica, Vettoretti, Simone, Fioretto, Paola, Carraro, Gianni, Farnia, Filippo, Postal, Anna, D'Amelio, Alessandro, Cardone, Antonio, Piccinni, Giovanni, Aloisi, Annalisa, Scolari, Francesco, Alberici, Federico, Guerini, Alice, Saccà, Chiara, Salviani, Chiara, Zani, Roberta, DE NICOLA, Luca, Garofalo, Carlo, Elena Liberti, Maria, Minutolo, Roberto, Pennino, Luigi, Polese, Lucio, Mené, Paolo, Barberi, Simona, Falcone, Clorinda, Russo, Francesco, Caroppo, Maurizio, Santorelli, Gennaro, Rivera, Rodolfo, Santoro, Domenico, Giuffrida, Alfio, Zirino, Fortunata, Calvi, Cristina, Estienne, Luca, Gambaro, Giovanni, Gangemi, Concetta, Ortalda, Vittorio, Pessolano, Giuseppina, Grandaliano, Giuseppe, Baccaro, Rocco, Ferraro, Pietro, Mangiacapra, Roberto, Melandri, Marco, Foligno, Nadia, Quartagno, Rita, Vezzoli, Giuseppe, Brioni, Elena, and Group, EMPA-KIDNEY Collaborative
Subjects: chronic renal disease, empagliflozin, empa-kidney, General Medicine
Abstract: Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; PConclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110. opens in new tab; EudraCT number, 2017-002971-24. opens in new tab.)
Published: 2023

42. Assessment of models for calculating the hydrodynamic radius of intrinsically disordered proteins

Author: Francesco Pesce, Estella A. Newcombe, Pernille Seiffert, Emil E. Tranchant, Johan G. Olsen, Christy R. Grace, Birthe B. Kragelund, and Kresten Lindorff-Larsen
Subjects: Biophysics
Abstract: Diffusion measurements by pulsed-field gradient NMR and fluorescence correlation spectroscopy can be used to probe the hydrodynamic radius of proteins, which contains information about the overall dimension of a protein in solution. The comparison of this value with structural models of intrinsically disordered proteins is nonetheless impaired by the uncertainty of the accuracy of the methods for computing the hydrodynamic radius from atomic coordinates. To tackle this issue, we here build conformational ensembles of 11 intrinsically disordered proteins that we ensure are in agreement with measurements of compaction by small-angle x-ray scattering. We then use these ensembles to identify the forward model that more closely fits the radii derived from pulsed-field gradient NMR diffusion experiments. Of the models we examined, we find that the Kirkwood-Riseman equation provides the best description of the hydrodynamic radius probed by pulsed-field gradient NMR experiments. While some minor discrepancies remain, our results enable better use of measurements of the hydrodynamic radius in integrative modeling and for force field benchmarking and parameterization. Diffusion measurements by pulsed-field gradient NMR and fluorescence correlation spectroscopy can be used to probe the hydrodynamic radius of proteins, which contains information about the overall dimension of a protein in solution. The comparison of this value with structural models of intrinsically disordered proteins is nonetheless impaired by the uncertainty of the accuracy of the methods for computing the hydrodynamic radius from atomic coordinates. To tackle this issue, we here build conformational ensembles of 11 intrinsically disordered proteins that we ensure are in agreement with measurements of compaction by small-angle x-ray scattering. We then use these ensembles to identify the forward model that more closely fits the radii derived from pulsed-field gradient NMR diffusion experiments. Of the models we examined, we find that the Kirkwood-Riseman equation provides the best description of the hydrodynamic radius probed by pulsed-field gradient NMR experiments. While some minor discrepancies remain, our results enable better use of measurements of the hydrodynamic radius in integrative modeling and for force field benchmarking and parameterization.
Published: 2023
Full Text: View/download PDF

43. Correction to 'Improving Martini 3 for Disordered and Multidomain Proteins'

Author: F. Emil Thomasen, Francesco Pesce, Mette Ahrensback Roesgaard, Giulio Tesei, and Kresten Lindorff-Larsen
Subjects: Physical and Theoretical Chemistry, Computer Science Applications
Published: 2023

44. [Quantitative imaging in nephrology: limits and potentials of elastosonography]

Author: Antonio, Granata, Giulio, Distefano, Rosario, Maccarrone, Francesco, Pesce, Giuseppa, Costanza, Antonio, Digiacomo, Antonio, Basile, Marcello, Romano, and Vito, Cantisani
Subjects: Nephrology, Elasticity Imaging Techniques, Humans, Renal Insufficiency, Chronic, Kidney, Fibrosis
Abstract: Chronic kidney disease is characterized by increasingly amplified fibrotic processes regardless of etiology. The severity of renal fibrosis seems to correlate with an increased risk of end-stage renal disease; therefore, monitoring of renal fibrosis over time may play an important role in the follow-up of both focal and diffuse renal diseases and in evaluating the response to treatments. Renal biopsy is the only method capable of providing objective and comparable information on the extent of fibrosis, but it is not suitable for outpatient monitoring of chronic kidney disease due to its invasiveness. Elastosonography is an innovative and non-invasive ultrasound method that allows the measurement of tissue elasticity through the transmission of mechanical waves and the measurement of their propagation speed. Although some authors have demonstrated the usefulness of elastosonographic techniques for the quantification of liver fibrosis, few studies have investigated the applications of elastosonography in renal pathology. Furthermore, the depth of native kidneys, the high anisotropy of the renal tissue, and the possibility of examining only a small region of interest currently limit its spread in clinical practice. The aim of this review is to examine the physical principles of elastosonography and to review the latest evidence about the possible applications of the ARFI (acoustic radiation force impulse) technique in the study of kidney diseases.
Published: 2022

45. Determination of the Upper Reference Limit of Human Epididymis Secretory Protein 4 (HE4) in Healthy Male Individuals and Correlation with Renal and Fertility Markers

Author: Loreto Gesualdo, Giuseppe Palmieri, Francesco Pesce, Annalisa Schirinzi, Andrea Ballini, Roberto Lovero, Luigi Santacroce, Francesca Di Serio, Elisa Mascolo, and Angela Pia Cazzolla
Subjects: Adult, Male, Percentile, Adolescent, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Population, Physiology, Renal function, Fertility, Kidney, Young Adult, WAP Four-Disulfide Core Domain Protein 2, medicine, Humans, Immunology and Allergy, education, Testosterone, Aged, media_common, education.field_of_study, business.industry, Middle Aged, Reference Standards, medicine.disease, Epididymis, medicine.anatomical_structure, Population study, Ovarian cancer, business, Biomarkers, Glomerular Filtration Rate
Abstract: Background: Elevated human epididymis secretory protein 4 (HE4) serum levels have been widely investigated in patients with ovarian cancer. However, high levels of HE4 can be also found in other tumors and in renal fibrosis. To date, the HE4 assay manufacturer features the reference value only for the female pre- and post-menopausal population. The aim of this study was to determine the upper reference limit (URL) of HE4 in a well-defined and large cohort of healthy male individuals and investigate potential factors influencing HE4 levels in healthy subjects. Methods: The study included 307 Italian healthy male individuals. HE4 was measured using a chemiluminescent assay (Abbott Laboratories, Wiesbaden, Germany). The URL was calculated using the non-parametric percentile method. Differences in HE4 concentrations according to age, estimated glomerular filtration rate (eGFR), free and bioavailable testosterone were also evaluated. Results: The 97.5th percentile URL of serum HE4 in our study population was 57 pmol/L (90% CI). After stratifying subjects according to age, we found that the URL of HE4 was higher in older (> 50 years) than in younger subjects (18-30 years old), and overlapping with the URL in males from 31 to 50 years old (P=4.769e-16, r=0.44). A strong negative correlation between HE4 and eGFR was observed (P=8.412e-12, r=- 0.38). Moreover, a statistically significant negative correlation was also found between HE4 and free and bioavailable testosterone. Conclusion: In this study was determined the URL of HE4 in a large cohort of healthy male subjects. Our findings indicate that the HE4 age-dependent differences in males need to be taken into account. The definition of the HE4 URL in males and the correlation observed with eGFR and testosterone should foster the clinical use of HE4 beyond gynecologic cancer.
Published: 2021

46. Gut-Derived Uremic Toxins in CKD: An Improved Approach for the Evaluation of Serum Indoxyl Sulfate in Clinical Practice

Author: Gianvito Caggiano, Loredana Amodio, Alessandra Stasi, Nicola Antonio Colabufo, Santina Colangiulo, Francesco Pesce, and Loreto Gesualdo
Subjects: Inorganic Chemistry, CKD, hemodialysis, uremic toxins, indoxyl sulfate, LC-MS/MS, Organic Chemistry, General Medicine, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Catalysis, Computer Science Applications
Abstract: In the past years, indoxyl sulfate has been strongly implicated in kidney disease progression and contributed to cardiovascular morbidity. Moreover, as a result of its elevated albumin affinity rate, indoxyl sulfate is not adequately cleared by extracorporeal therapies. Within this scenario, although LC-MS/MS represents the conventional approach for IS quantification, it requires dedicated equipment and expert skills and does not allow real-time analysis. In this pilot study, we implemented a fast and simple technology designed to determine serum indoxyl sulfate levels that can be integrated into clinical practice. Indoxyl sulfate was detected at the time of enrollment by Tandem MS from 25 HD patients and 20 healthy volunteers. Next, we used a derivatization reaction to transform the serum indoxyl sulfate into Indigo blue. Thanks to the spectral shift to blue, its quantity was measured by the colorimetric assay at a wavelength of 420–450 nm. The spectrophotometric analysis was able to discriminate the levels of IS between healthy subjects and HD patients corresponding to the LC-MS/MS. In addition, we found a strong linear relationship between indoxyl sulfate levels and Indigo levels between the two methods (Tandem MS and spectrophotometry). This innovative method in the assessment of gut-derived indoxyl sulfate could represent a valid tool for clinicians to monitor CKD progression and dialysis efficacy.
Published: 2023

47. COME SE VEDESSE IL POSSIBILE. CONTRIBUTO PER UNA GAUDIUMTHEOLOGIE

Author: Francesco Pesce
Abstract: L’articolo prende in esame i discorsi di papa Francesco rivolti a teologi o concernenti la teologia stessa, allo scopo di evidenziare lo specifico servizio della riflessione teologica all’interno della prospettiva evangelizzatrice. Su questa base vengono enucleati tre elementi per una teologia rinnovata, a servizio della gioia degli uomini e delle donne di oggi, capace di contribuire alla costruzione della convivenza tra i popoli.
Published: 2020

48. FC073: An Epigenetically Driven Mechanism Triggered by Viral and Bacterial RNA Regulates the IL-6 Levels in IGA Nephropathy

Author: Fabio Sallustio, Claudia Curci, Maria Teresa Cimmarusti, Angela Picerno, Francesca Giannuzzi, Giuseppe De Palma, Carmen Sivo, Francesca Annese, Giulia Fonto, Silvio Tafuri, Iris Cara, Vincenzo Barone, Alessandra Stasi, Francesco Pesce, Vincenzo DI Leo, and Loreto Gesualdo
Subjects: Transplantation, Nephrology
Abstract: BACKGROUND AND AIMS Several models have been proposed to describe the pathogenesis of Immunoglobulin A nephropathy (IgAN) and, among them, the multihit model where the gut-microbiota may play an important role. These models explain the pathogenesis of IgAN caused by the production of aberrant IgA, but it is believed that further predisposing factors are present, including immunological, genetic, environmental or nutritional factors. Recently, the role of IL-6 in IgAN pathogenesis is becoming increasingly important. It is essential for the deposition of glomerular immunoglobulin A and the development of renal disease in Cd37-deficient mice, although the pathogenetic mechanisms that determine its increase are not well known. A possible hypothesis emerges from our recent work on genome-wide DNA methylation screening in patients with IgAN, which identified, among other findings, a hypermethylated region comprising Vault 2–1 RNA (VTRNA2-1), a non-RNA coding also known as a precursor of miR-886 (pre-mi-RNA). Consistently, VTRNA2-1 expression was found downregulated in IgAN patients. Here we studied the involvement of the VTRNA2-1/PKR/CREB/IL-6 pathway in IgAN. METHOD Total RNA were isolated from PBMCs of IgAN patients, transplanted IgAN patients (TP-IgAN), non-IgAN transplanted patients (TP) and healthy subjects (HS). VTRNA2-1, CREB and PKR transcripts were evaluated by RT-PCR. Total and phosphorylated PKR, CREB and Il-6 proteins were evaluated by ELISA. Poly (I: C), a synthetic analogue of dsRNA and Pfizer-BioNTech COVID-19 COMIRNATY vaccine were used to transfect patient PBMCs. PKR inhibitor imoxin (C16) 1 µM was used to stimulate patient PBMCs. RESULTS Here we confirm that VTRNA2-1 transcript was down-regulated in native and transplanted IgAN subjects compared to HS and non IgAN transplanted patients, with a decrease of 30- and 100-folds, respectively (P Since PKR is normally activated by bacterial and viral RNA, we hypothesized that these microorganisms can further activate the PKR/CREB/IL-6 pathway leading to an excess of IL-6 production. This may explain both the high levels of IL-6, and infection involvement in the disease, and cases of IgAN associated with COVID-19 infection or with COVID-19 RNA-vaccination, and recent data showing microbiota involvement in IgAN. Effectively, we found that IgAN PMBCs stimulated with RNA poly(I: C) or the COVID-19 RNA-vaccine showed a significant increase in IL-6 levels compared to not-stimulated PBMCs (P Finally, we showed that the IL-6 secretion can be reduced by the PKR inhibitor imoxin (fold decrease of 5-folds in IgAN and TP-IgAN patients; P CONCLUSION In conclusion, the discovery of the upregulated VTRNA2-1/PKR/CREB/IL-6 pathway in IgAN patients may provide a new pathogenic mechanism in IgAN and may be useful for the development of novel therapeutic approaches, likely by modulating the VTRNA2-1 methylation level in IgAN patients.
Published: 2022

49. MO611: Glycated Albumin Levels Predict The Type of Kidney Damage in Diabetic Patients

Author: Paola Pontrelli, Mauro Fiume, Francesca Conserva, Claudia Cinefra, Francesco Pesce, Annalisa Schirinzi, Francesca D I Serio, and Loreto Gesualdo
Subjects: Transplantation, Nephrology
Abstract: BACKGROUND AND AIMS Diabetes mellitus remains the most frequent cause of end-stage renal disease (ESRD) in developing countries. The main determinant of the onset of nephropathy in diabetes is hyperglycemia which brings to glycation of albumin and haemoglobin with higher concentration of AGEs (advanced glycation end products), finally leading to fibrosis, inflammation and albuminuria. Glycated albumin (GA) was introduced as an alternative to hemoglobin A1c (HbA1c) for glycemic control in the CKD population, with some advantages for diabetic patients with diabetic kidney disease (DKD), since it is not influenced by anemia and associated treatments and it is not affected by serum albumin levels. Although some evidences in literature demonstrated that GA is superior to HbA1c in assessing blood glucose control in DKD (Gan T et al. J Diabetes Complications. 2018); however, KDIGO Guidelines still recommend HbA1c, although underlying some limitations in the context of DKD, meaning that new markers are needed in order to monitor this class of diabetic patients. Kidney disease in diabetic patients can include different kind of renal damage ranging from real diabetic nephropathy (DN, with Kimmelstiel–Wilson lesions, glomerular basal membrane thickening, proliferation of mesangial matrix) to nondiabetic renal disease (NDRD), in the presence or absence of real DN, thus influencing prognosis and treatment. The purpose of the study was to evaluate the clinical utility of the GA dosage, alone or with other molecular and clinical markers as noninvasive biomarkers for the prediction of the progression and type of kidney damage in the diabetic patient. METHOD We enrolled 108 diabetic patients in follow-up at our center, 90 with a biopsy-proven diagnosis of kidney disease and 18 with no kidney dysfunction. Among the 90 patients, 51 had real diabetic nephropathy (DN) or mixed forms (DN + NDRD) and 39 had non-diabetic renal disease (NDRD). GA dosage was obtained by QuantILab® Glycated Albumin assay (Instrumentation Laboratory SpA, Milan, Italy). qPCR was used to evaluate urinary levels of miR27b-3p, a biomarker that predicts the kind of renal damage in diabetic patients and is related to kidney fibrosis (Conserva F et al. Sci Rep. 2019). Statistical analysis was performed using ‘SPSS Statistical Software.’ RESULTS We observed that GA values had a significantly different distribution among DN, NDRD and diabetic patients without renal dysfunction (P = 0.003); conversely, there was no statistical difference in HbA1c distribution although a trend was visible. In the entire cohort, only GA levels, but not HbA1c levels, were significantly correlated with fasting glucose (P = 0.001) and the duration of diabetes (P = .001). In the single classes, only in DN patients there was a significant correlation between GA and diabetes duration (P = .02) and GA and HbA1c (P = 0.01) but not in the NDRD class (P = 0.43). We then applied a multivariate logistic regression model to discriminate real DN and NDRD. We demonstrated that GA is the only significant predictor of real DN in a model corrected for sex, age and serum creatinine {P = 0.009; OR = 0.757–0.962; [95% confidence interval (CI)]}, whereas the same logistic regression model with HbA1c demonstrated no significance (P = 0.082). In the same cohort, we also evaluated miR-27b-3p expression levels, whose levels are correlated with renal fibrosis in DN, and we observed that there was a significant and direct correlation also with GA levels (P = 0.001), thus suggesting the possibility to integrate these biomarkers to predict the kind of renal damage in diabetic patients. CONCLUSION Our study described for the first time the role played by GA as a diagnostic marker in the identification of the different kind of renal damage in diabetic patients. All these evidences support the need to introduce GA as an index of glycemic control to be associated with other molecular markers, such as miRNAs, in order to noninvasively diagnose the kind of renal damage in diabetic patients.
Published: 2022

50. MO616: The Genetic Background Predicts The Kind of Renal Damage and Fibrosis Progression in Diabetic Patients

Author: Paola Pontrelli, Claudia Cinefra, Francesca Conserva, Mauro Fiume, Anna Gallone, Francesco Pesce, and Loreto Gesualdo
Subjects: Transplantation, Nephrology
Abstract: BACKGROUND AND AIMS Diabetic Nephropathy (DN) is the major causes of end-stage renal failure. DN diagnosis is based on typical histological features (Kimmelstiel–Wilson lesions, glomerular basal membrane thickening and proliferation of mesangial matrix). Not all diabetic patients with kidney disease develop true DN: kidney impairment can be due to a nondiabetic renal disease (NDRD) in the presence or absence of real DN. Thus, there is the need for noninvasive biomarkers, related to specific pathogenic processes, to discriminate DN and NDRD, and/or to predict DN onset. In the case of DN, there is extensive evidence in literature of genetic contribution to disease susceptibility and lots of efforts aim at the identification of specific loci. The research group demonstrated that a characteristic feature of DN is an increase in Lys63-ubiquitinated proteins at tubular level that leads to epithelial-to-mesenchymal transition (EMT) and finally to the progression of the tubular-interstitial fibrosis and the renal damage in DN patients (Pontrelli P et al. FASEB J 2017). Ube2V1 is the unique E2 enzyme known for producing Lys63-linked ubiquitin chains. Moreover, two miRNAs (miR27b-3p e miR1228-3p), which interact specifically with Ube2V1 transcript, predict the type of renal damage in diabetic patients and are related with kidney fibrosis (Conserva F et al. Sci Rep 2019). The goal of this project was to identify single nucleotide polymorphisms (SNPs) able to predict the different kind of renal damage and the progression of kidney disease in diabetic patients. METHOD We selected by UCSC genome, 10 HapMap SNPs of patients within coding and regulatory sequences both of miR27b-3p and miR1228-3p and Ube2V1 gene in order to evaluate their diagnostic and prognostic potential. The patients enrolled in this study were diabetic patients with a biopsy-proven DN diagnosis (DN), diabetic patients with a biopsy-proven diagnosis of other nephropathy than DN (NDRD), diabetic patients without clinical signs of impaired renal function (T2D), diabetic patients with a biopsy-proven coexistence of both conditions (ND + NDRD), non-diabetic patients with glomerulonephritis (CKD), non-diabetic patients without renal damage (CTRL). The DNA of 201 subjects (patients and controls) was isolated from blood samples, and 10 HapMap SNPs (rs3802456, rs4744422, rs10761364, rs7853195 in the control region of miR27b-3p; rs2306692, rs4759277, rs4759044, rs17547610, rs4759275 in the control region of miR1228-3p; rs761214 in the UBE2v1 gene) for each patient were analyzed using TaqMan real-time PCR. Glomerular and tubulointerstitial fibrosis in kidney biopsies was quantified on Sirius Red staining using the Aperio Imagescope software. RESULTS The analyzed SNPs showed a different genotype frequency among all the patients’ classes. Interestingly, SNPs rs4759275, rs4759277, rs4744422 and rs3802456 showed a statistically significant difference in genotype frequency comparing DN patients with CEU Population (Northern and Western European Ancestry in Utah) (P CONCLUSION Our data demonstrated that the allelic forms of the analyzed SNPs are related to the different kind of renal damage in diabetic patients. Their prognostic and diagnostic potential could represent the starting point to create a new noninvasive diagnosis system based on clinical and genotyping data.
Published: 2022

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

168 results on '"Francesco Pesce"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources