Publications by authors named "Claudio Angelini"

43 Publications

Outstanding Pinkish Brown-Spored Neotropical Boletes: and (Boletaceae, Boletales) from the Dominican Republic.

Mycobiology 2020 Nov 16;49(1):24-45. Epub 2020 Nov 16.

Department of Life Science and Systems Biology, University of Turin, Torino, Italy.

The occurrence of and is documented from the Dominican Republic. The latter species is reported for the first time outside its original locality in Martinique, extending the geographic range for this uncommon pinkish-spored bolete. A detailed morphological description is provided for each species and accompanied by color pictures of fresh basidiomes in habitat and line drawings of the main anatomical features. Both species represent independent lineages within their respective genera based on phylogenetic inference. In addition, clusters in a sister lineage to the core clade ( clade I) here named as clade II. In order to confirm the accuracy of species identification, their identity and relationships were subjected to multilocus phylogenetic analyses of three gene markers (ITS, nrLSU, RPB2) including genetic material already available in public databases. is a widely distributed species in North and Central America, whereas is apparently highly localized and seems to appear sparingly in the Dominican Republic, Martinque, and southern Florida. Comparisons with morphologically similar and molecularly inferred allied species are also presented and discussed.
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http://dx.doi.org/10.1080/12298093.2020.1843221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832513PMC
November 2020

The genera and in the Dominican Republic.

Mycologia 2021 Mar-Apr;113(2):348-389. Epub 2021 Jan 22.

Via A. Volta 31, 36075 Alte di Montecchio Maggiore, VI, Italy.

We studied species of and collected in the Dominican Republic over the past 10 years using morphological and molecular methods and carefully compared our collections with previously described neotropical taxa. Twelve new species, eight in () and four in () are described. Additional records of previously described taxa are also discussed, including the first molecularly annotated occurrences of , and in their putative natural habitats and of in the neotropics. and are transferred here to based on their phylogenetic placement and morphological characteristics. Color photographs of fresh basidiocarps and line drawings of microscopic characters are provided for all species.
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http://dx.doi.org/10.1080/00275514.2020.1819142DOI Listing
January 2021

Plasma Protein Carbonyls as Biomarkers of Oxidative Stress in Chronic Kidney Disease, Dialysis, and Transplantation.

Oxid Med Cell Longev 2020 24;2020:2975256. Epub 2020 Nov 24.

Department of Biosciences (Department of Excellence 2018-2022), Università degli Studi di Milano, Milan I-20133, Italy.

Accumulating evidence indicates that oxidative stress plays a role in the pathophysiology of chronic kidney disease (CKD) and its progression; during renal replacement therapy, oxidative stress-derived oxidative damage also contributes to the development of CKD systemic complications, such as cardiovascular disease, hypertension, atherosclerosis, inflammation, anaemia, and impaired host defence. The main mechanism underlying these events is the retention of uremic toxins, which act as a substrate for oxidative processes and elicit the activation of inflammatory pathways targeting endothelial and immune cells. Due to the growing worldwide spread of CKD, there is an overwhelming need to find oxidative damage biomarkers that are easy to measure in biological fluids of subjects with CKD and patients undergoing renal replacement therapy (haemodialysis, peritoneal dialysis, and kidney transplantation), in order to overcome limitations of invasive monitoring of CKD progression. Several studies investigated biomarkers of protein oxidative damage in CKD, including plasma protein carbonyls (PCO), the most frequently used biomarker of protein damage. This review provides an up-to-date overview on advances concerning the correlation between plasma protein carbonylation in CKD progression (from stage 1 to stage 5) and the possibility that haemodialysis, peritoneal dialysis, and kidney transplantation improve plasma PCO levels. Despite the fact that the role of plasma PCO in CKD is often underestimated in clinical practice, emerging evidence highlights that plasma PCO can serve as good biomarkers of oxidative stress in CKD and substitutive therapies. Whether plasma PCO levels merely serve as biomarkers of CKD-related oxidative stress or whether they are associated with the pathogenesis of CKD complications deserves further evaluation.
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http://dx.doi.org/10.1155/2020/2975256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707964PMC
November 2020

Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19.

Nat Immunol 2021 01 18;22(1):19-24. Epub 2020 Nov 18.

Humanitas Clinical and Research Center-IRCCS, Milan, Italy.

Long pentraxin 3 (PTX3) is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation. The present study was designed to assess the presence and significance of PTX3 in Coronavirus Disease 2019 (COVID-19). RNA-sequencing analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry of lung autopsy samples revealed that myelomonocytic cells and endothelial cells express high levels of PTX3 in patients with COVID-19. Increased plasma concentrations of PTX3 were detected in 96 patients with COVID-19. PTX3 emerged as a strong independent predictor of 28-d mortality in multivariable analysis, better than conventional markers of inflammation, in hospitalized patients with COVID-19. The prognostic significance of PTX3 abundance for mortality was confirmed in a second independent cohort (54 patients). Thus, circulating and lung myelomonocytic cells and endothelial cells are a major source of PTX3, and PTX3 plasma concentration can serve as an independent strong prognostic indicator of short-term mortality in COVID-19.
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http://dx.doi.org/10.1038/s41590-020-00832-xDOI Listing
January 2021

Biomarkers and Diagnostic Testing for Renal Disease in Sjogren's Syndrome.

Front Immunol 2020 17;11:562101. Epub 2020 Sep 17.

Department of Nephrology, Humanitas Clinical and Research Center - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.

Primary Sjogren's syndrome (pSS) is an autoimmune disorder in which lymphocytic infiltration leads to lacrimal and salivary glands dysfunction, which results in symptoms of dryness (xerophthalmia and xerostomia). Extraglandular features are common and may affect several organs. Renal involvement has long been known as one of the systemic complications of pSS. The most classical lesion observed in pSS is tubulointerstitial nephritis (TIN) and less frequently membranoproliferative glomerulonephritis (MPGN), which is related to cryoglobulinemia. In some cases, renal biopsy is necessary for the definitive diagnosis of kidney involvement. Patients may present with proximal renal tubular acidosis, distal renal tubular acidosis and chronic kidney disease. Response to treatment is usually favorable. However, occasionally severe and rarely lethal outcomes have been described. Recently, several case series and cross-sectional studies have been published which investigated the factors associated with renal involvement in pSS and the most accurate screening tests for early detection. The presence of xerophthalmia, anti-SSA and rheumatoid factor positivity, low C3 levels and other features have all shown either positive or inverse associations with the development of renal complications. Serum creatinine, alpha-1-microglobulin, cystatin-C have been evaluated as early detection biomarkers with variable accuracy. More advanced techniques may be necessary to confirm proximal and distal renal tubular acidosis, along with nephrogenic diabetes insipidus. The aim of the current paper is to summarize and critically examine these findings in order to provide updated guidance on serum biomarkers and further testing for kidney involvement in pSS.
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http://dx.doi.org/10.3389/fimmu.2020.562101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527442PMC
September 2020

Phylotranscriptomic evidence for pervasive ancient hybridization among Old World salamanders.

Mol Phylogenet Evol 2021 02 6;155:106967. Epub 2020 Oct 6.

Zoological Institute, Technische Universität Braunschweig, Mendelssohnstr. 4, 38106 Braunschweig, Germany.

Hybridization can leave genealogical signatures in an organism's genome, originating from the parental lineages and persisting over time. This potentially confounds phylogenetic inference methods that aim to represent evolution as a strictly bifurcating tree. We apply a phylotranscriptomic approach to study the evolutionary history of, and test for inter-lineage introgression in the Salamandridae, a Holarctic salamanders group of interest in studies of toxicity and aposematism, courtship behavior, and molecular evolution. Although the relationships between the 21 currently recognized salamandrid genera have been the subject of numerous molecular phylogenetic studies, some branches have remained controversial and sometimes affected by discordances between mitochondrial vs. nuclear trees. To resolve the phylogeny of this family, and understand the source of mito-nuclear discordance, we generated new transcriptomic (RNAseq) data for 20 salamandrids and used these along with published data, including 28 mitochondrial genomes, to obtain a comprehensive nuclear and mitochondrial perspective on salamandrid evolution. Our final phylotranscriptomic data set included 5455 gene alignments for 40 species representing 17 of the 21 salamandrid genera. Using concatenation and species-tree phylogenetic methods, we find (1) Salamandrina sister to the clade of the "True Salamanders" (consisting of Chioglossa, Mertensiella, Lyciasalamandra, and Salamandra), (2) Ichthyosaura sister to the Near Eastern genera Neurergus and Ommatotriton, (3) Triturus sister to Lissotriton, and (4) Cynops paraphyletic with respect to Paramesotriton and Pachytriton. Combining introgression tests and phylogenetic networks, we find evidence for introgression among taxa within the clades of "Modern Asian Newts" and "Modern European Newts". However, we could not unambiguously identify the number, position, and direction of introgressive events. Combining evidence from nuclear gene analysis with the observed mito-nuclear phylogenetic discordances, we hypothesize a scenario with hybridization and mitochondrial capture among ancestral lineages of (1) Lissotriton into Ichthyosaura and (2) Triturus into Calotriton, plus introgression of nuclear genes from Triturus into Lissotriton. Furthermore, both mitochondrial capture and nuclear introgression may have occurred among lineages assigned to Cynops. More comprehensive genomic data will, in the future, allow testing this against alternative scenarios involving hybridization with other, extinct lineages of newts.
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http://dx.doi.org/10.1016/j.ympev.2020.106967DOI Listing
February 2021

The role of anti-hypertensive treatment, comorbidities and early introduction of LMWH in the setting of COVID-19: A retrospective, observational study in Northern Italy.

Int J Cardiol 2021 02 25;324:249-254. Epub 2020 Sep 25.

Emergency Department, Humanitas Clinical and Research Center, IRCCS, Milan, Italy.

Background: There is a great deal of debate about the role of cardiovascular comorbidities and the chronic use of antihypertensive agents (such as ACE-I and ARBs) on mortality on COVID-19 patients. Of note, ACE2 is responsible for the host cell entry of the virus.

Methods: We extracted data on 575 consecutive patients with laboratory-confirmed SARS-CoV-2 infection admitted to the Emergency Department (ED) of Humanitas Center, between February 21 and April 14, 2020. The aim of the study was to evaluate the role of chronic treatment with ACE-I or ARBs and other clinical predictors on in-hospital mortality in a cohort of COVID-19 patients.

Results: Multivariate analysis showed that a chronic intake of ACE-I was associated with a trend in reduction of mortality (OR: 0.53; 95% CI: 0.27-1.03; p = 0.06), differently from a chronic intake of ARB (OR: 1.1; 95% CI: 0.5-2.8; p=0.8). Increased age (ORs ranging from 3.4 to 25.2 and to 39.5 for 60-70, 70-80 and >80 years vs <60) and cardiovascular comorbidities (OR: 1.90; 95% CI: 1.1-3.3; p = 0.02) were confirmed as important risk factors for COVID-19 mortality. Timely treatment with low-molecular-weight heparin (LMWH) in ED was found to be protective (OR: 0.36; 95% CI: 0.21-0.62; p < 0.0001).

Conclusions: This study can contribute to understand the reasons behind the high mortality rate of patients in Lombardy, a region which accounts for >50% of total Italian deaths. Based on our findings, we support that daily intake of antihypertensive medications in the setting of COVID-19 should not be discontinued and that a timely LMWH administration in ED has shown to decrease in-hospital mortality.
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http://dx.doi.org/10.1016/j.ijcard.2020.09.062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516574PMC
February 2021

First Report of a Neotropical Agaric (, Agaricales, Basidiomycota) Containing Lethal α-Amanitin at Toxicologically Relevant Levels.

Front Microbiol 2020 11;11:1833. Epub 2020 Aug 11.

Department of Pharmacology, Faculty of Medicine, Duzce University, Duzce, Turkey.

A recent collection of from the Dominican Republic is presented here. Macro- and micromorphological features of are described in detail, and its evolutionary (phylogenetic) position within sect. , in the subincarnata/brunneoincarnata clade, is assessed on the basis of a combined nrLSU + nrITS + + analysis. Additionally, high levels of deadly amatoxins were detected and quantified in for the first time by HPLC analysis; in particular, α-amanitin was found at concentrations up to approximately 4 mg/g dry weight, which render a potentially lethal mushroom, if ingested.
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http://dx.doi.org/10.3389/fmicb.2020.01833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432468PMC
August 2020

Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients.

J Autoimmun 2020 11 8;114:102511. Epub 2020 Jul 8.

Humanitas University, Department of Biomedical Sciences, Pieve Emanuele (MI), Italy; Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center- IRCCS, Rozzano (MI), Italy. Electronic address:

In cases of COVID-19 acute respiratory distress syndrome, an excessive host inflammatory response has been reported, with elevated serum interleukin-6 levels. In this multicenter retrospective cohort study we included adult patients with COVID-19, need of respiratory support, and elevated C-reactive protein who received intravenous tocilizumab in addition to standard of care. Control patients not receiving tocilizumab were matched for sex, age and respiratory support. We selected survival as the primary endpoint, along with need for invasive ventilation, thrombosis, hemorrhage, and infections as secondary endpoints at 30 days. We included 64 patients with COVID-19 in the tocilizumab group and 64 matched controls. At baseline the tocilizumab group had longer symptom duration (13 ± 5 vs. 9 ± 5 days) and received hydroxychloroquine more often than controls (100% vs. 81%). The mortality rate was similar between groups (27% with tocilizumab vs. 38%) and at multivariable analysis risk of death was not significantly influenced by tocilizumab (hazard ratio 0.61, 95% confidence interval 0.33-1.15), while being associated with the use at baseline of non invasive mechanical or invasive ventilation, and the presence of comorbidities. Among secondary outcomes, tocilizumab was associated with a lower probability of requiring invasive ventilation (hazard ratio 0.36, 95% confidence interval 0.16-0.83; P = 0.017) but not with the risk of thrombosis, bleeding, or infections. The use of intravenous tocilizumab was not associated with changes in 30-day mortality in patients with COVID-19 severe respiratory impairment. Among the secondary outcomes there was less use of invasive ventilation in the tocilizumab group.
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http://dx.doi.org/10.1016/j.jaut.2020.102511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342030PMC
November 2020

Looks can be deceiving: the deceptive milkcaps (, Russulaceae) exhibit low morphological variance but harbour high genetic diversity.

IMA Fungus 2019 18;10:14. Epub 2019 Sep 18.

Department of Biology, Research group Mycology, Ghent University, K.L. Ledeganckstraat 35, 9000 Ghent, Belgium.

The ectomycorrhizal genus is known to contain many species complexes, consisting of morphologically very similar species, which can be considered cryptic or pseudocryptic. In this paper, a thorough molecular study is performed of the clade around (originally described by Peck from North America) or the deceptive milkcaps. Even though most collections were identified as , the clade is shown to contain at least 15 species, distributed across Asia and America, indicating that the clade represents a species complex. These species are morphologically very similar and are characterized by a tomentose pileus with thin-walled hyphae and a velvety stipe with thick-walled hyphae. An ITS1 sequence was obtained through Illumina sequencing for the lectotype of , dating from 1885, revealing which clade represents the true . In addition, it is shown that three other described species also belong to the clade: , and and molecularly confirmed that represents a synonym of . Furthermore, two new Neotropical species are described: and .
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http://dx.doi.org/10.1186/s43008-019-0017-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325672PMC
September 2019

Genomewide Association Study of Severe Covid-19 with Respiratory Failure.

Authors:
David Ellinghaus Frauke Degenhardt Luis Bujanda Maria Buti Agustín Albillos Pietro Invernizzi Javier Fernández Daniele Prati Guido Baselli Rosanna Asselta Marit M Grimsrud Chiara Milani Fátima Aziz Jan Kässens Sandra May Mareike Wendorff Lars Wienbrandt Florian Uellendahl-Werth Tenghao Zheng Xiaoli Yi Raúl de Pablo Adolfo G Chercoles Adriana Palom Alba-Estela Garcia-Fernandez Francisco Rodriguez-Frias Alberto Zanella Alessandra Bandera Alessandro Protti Alessio Aghemo Ana Lleo Andrea Biondi Andrea Caballero-Garralda Andrea Gori Anja Tanck Anna Carreras Nolla Anna Latiano Anna Ludovica Fracanzani Anna Peschuck Antonio Julià Antonio Pesenti Antonio Voza David Jiménez Beatriz Mateos Beatriz Nafria Jimenez Carmen Quereda Cinzia Paccapelo Christoph Gassner Claudio Angelini Cristina Cea Aurora Solier David Pestaña Eduardo Muñiz-Diaz Elena Sandoval Elvezia M Paraboschi Enrique Navas Félix García Sánchez Ferruccio Ceriotti Filippo Martinelli-Boneschi Flora Peyvandi Francesco Blasi Luis Téllez Albert Blanco-Grau Georg Hemmrich-Stanisak Giacomo Grasselli Giorgio Costantino Giulia Cardamone Giuseppe Foti Serena Aneli Hayato Kurihara Hesham ElAbd Ilaria My Iván Galván-Femenia Javier Martín Jeanette Erdmann Jose Ferrusquía-Acosta Koldo Garcia-Etxebarria Laura Izquierdo-Sanchez Laura R Bettini Lauro Sumoy Leonardo Terranova Leticia Moreira Luigi Santoro Luigia Scudeller Francisco Mesonero Luisa Roade Malte C Rühlemann Marco Schaefer Maria Carrabba Mar Riveiro-Barciela Maria E Figuera Basso Maria G Valsecchi María Hernandez-Tejero Marialbert Acosta-Herrera Mariella D'Angiò Marina Baldini Marina Cazzaniga Martin Schulzky Maurizio Cecconi Michael Wittig Michele Ciccarelli Miguel Rodríguez-Gandía Monica Bocciolone Monica Miozzo Nicola Montano Nicole Braun Nicoletta Sacchi Nilda Martínez Onur Özer Orazio Palmieri Paola Faverio Paoletta Preatoni Paolo Bonfanti Paolo Omodei Paolo Tentorio Pedro Castro Pedro M Rodrigues Aaron Blandino Ortiz Rafael de Cid Ricard Ferrer Roberta Gualtierotti Rosa Nieto Siegfried Goerg Salvatore Badalamenti Sara Marsal Giuseppe Matullo Serena Pelusi Simonas Juzenas Stefano Aliberti Valter Monzani Victor Moreno Tanja Wesse Tobias L Lenz Tomas Pumarola Valeria Rimoldi Silvano Bosari Wolfgang Albrecht Wolfgang Peter Manuel Romero-Gómez Mauro D'Amato Stefano Duga Jesus M Banales Johannes R Hov Trine Folseraas Luca Valenti Andre Franke Tom H Karlsen

N Engl J Med 2020 10 17;383(16):1522-1534. Epub 2020 Jun 17.

From the Institute of Clinical Molecular Biology, Christian-Albrechts-University (D.E., F.D., J.K., S. May, M. Wendorff, L.W., F.U.-W., X.Y., A.T., A. Peschuck, C.G., G.H.-S., H.E.A., M.C.R., M.E.F.B., M. Schulzky, M. Wittig, N.B., S.J., T.W., W.A., M. D'Amato, A.F.), and University Hospital Schleswig-Holstein, Campus Kiel (N.B., A.F.), Kiel, the Institute for Cardiogenetics, University of Lübeck, Lübeck (J.E.), the German Research Center for Cardiovascular Research, partner site Hamburg-Lübeck-Kiel (J.E.), the University Heart Center Lübeck (J.E.), and the Institute of Transfusion Medicine, University Hospital Schleswig-Holstein (S.G.), Lübeck, Stefan-Morsch-Stiftung, Birkenfeld (M. Schaefer, W.P.), and the Research Group for Evolutionary Immunogenomics, Max Planck Institute for Evolutionary Biology, Plön (O.O., T.L.L.) - all in Germany; Novo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (D.E.); the Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute-Donostia University Hospital-University of the Basque Country (L.B., K.G.-E., L.I.-S., P.M.R., J.M.B.), Osakidetza Basque Health Service, Donostialdea Integrated Health Organization, Clinical Biochemistry Department (A.G.C., B.N.J.), and the Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute (M. D'Amato), San Sebastian, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III (L.B., M. Buti, A. Albillos, A. Palom, F.R.-F., B.M., L. Téllez, K.G.-E., L.I.-S., F.M., L.R., M.R.-B., M. Rodríguez-Gandía, P.M.R., M. Romero-Gómez, J.M.B.), the Departments of Gastroenterology (A. Albillos, B.M., L. Téllez, F.M., M. Rodríguez-Gandía), Intensive Care (R.P., A.B.O.), Respiratory Diseases (D.J., A.S., R.N.), Infectious Diseases (C.Q., E.N.), and Anesthesiology (D. Pestaña, N. Martínez), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, University of Alcalá, and Histocompatibilidad y Biologia Molecular, Centro de Transfusion de Madrid (F.G.S.), Madrid, the Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus (M. Buti, A. Palom, L.R., M.R.-B.), Hospital Clinic, University of Barcelona, and the August Pi i Sunyer Biomedical Research Institute (J.F., F.A., E.S., J.F.-A., L.M., M.H.-T., P.C.), the European Foundation for the Study of Chronic Liver Failure (J.F.), Vall d'Hebron Institut de Recerca (A. Palom, F.R.-F., A.J., S. Marsal), and the Departments of Biochemistry (A.-E.G.-F., F.R.-F., A.C.-G., C.C., A.B.-G.), Intensive Care (R.F.), and Microbiology (T.P.), University Hospital Vall d'Hebron, the Immunohematology Department, Banc de Sang i Teixits, Autonomous University of Barcelona (E.M.-D.), Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Consortium for Biomedical Research in Epidemiology and Public Health and University of Barcelona, l'Hospitalet (V. Moreno), and Autonoma University of Barcelona (T.P.), Barcelona, Universitat Autònoma de Barcelona, Bellatera (M. Buti, F.R.-F., M.R.-B.), GenomesForLife-GCAT Lab Group, Germans Trias i Pujol Research Institute (A.C.N., I.G.-F., R.C.), and High Content Genomics and Bioinformatics Unit, Germans Trias i Pujol Research Institute (L. Sumoy), Badalona, Institute of Parasitology and Biomedicine Lopez-Neyra, Granada (J.M., M.A.-H.), the Digestive Diseases Unit, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville, University of Seville, Seville (M. Romero-Gómez), and Ikerbasque, Basque Foundation for Science, Bilbao (M. D'Amato, J.M.B.) - all in Spain; the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan Bicocca (P.I., C.M.), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (D. Prati, G.B., A.Z., A. Bandera, A.G., A.L.F., A. Pesenti, C.P., F.C., F.M.-B., F.P., F.B., G.G., G. Costantino, L. Terranova, L. Santoro, L. Scudeller, M. Carrabba, M. Baldini, M.M., N. Montano, R.G., S.P., S. Aliberti, V. Monzani, S. Bosari, L.V.), the Department of Biomedical Sciences, Humanitas University (R.A., A. Protti, A. Aghemo, A. Lleo, E.M.P., G. Cardamone, M. Cecconi, V.R., S.D.), Humanitas Clinical and Research Center, IRCCS (R.A., A. Protti, A. Aghemo, A. Lleo, A.V., C.A., E.M.P., H.K., I.M., M. Cecconi, M. Ciccarelli, M. Bocciolone, P.P., P.O., P.T., S. Badalamenti, S.D.), University of Milan (A.Z., A. Bandera, A.G., A.L.F., A. Pesenti, F.M.-B., F.P., F.B., G.G., G. Costantino, M.M., N. Montano, R.G., S.P., S. Aliberti, S. Bosari, L.V.), and the Center of Bioinformatics, Biostatistics, and Bioimaging (M.G.V.) and the Phase 1 Research Center (M. Cazzaniga), School of Medicine and Surgery, and the Departments of Emergency, Anesthesia, and Intensive Care (G.F.), Pneumologia (P.F.), and Infectious Diseases (P.B.); University of Milano-Bicocca, Milan, the European Reference Network on Hepatological Diseases (P.I., C.M.) and the Infectious Diseases Unit (P.B.), San Gerardo Hospital, Monza, the Pediatric Departement and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale, San Gerardo (A. Biondi, L.R.B., M. D'Angiò), the Gastroenterology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (A. Latiano, O.P.), the Department of Medical Sciences, Università degli Studi di Torino, Turin (S. Aneli, G.M.), and the Italian Bone Marrow Donor Registry, E.O. Ospedali Galliera, Genoa (N.S.) - all in Italy; the Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases, and Transplantation, and the Research Institute for Internal Medicine, Division of Surgery, Inflammatory Diseases, and Transplantation, Oslo University Hospital Rikshospitalet and University of Oslo (M.M.G., J.R.H., T.F., T.H.K.), and the Section for Gastroenterology, Department of Transplantation Medicine, Division for Cancer Medicine, Surgery, and Transplantation, Oslo University Hospital Rikshospitalet (J.R.H., T.F., T.H.K.), Oslo; the School of Biological Sciences, Monash University, Clayton, VIC, Australia (T.Z., M. D'Amato); Private University in the Principality of Liechtenstein (C.G.); the Institute of Biotechnology, Vilnius University, Vilnius, Lithuania (S.J.); and the Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm (M. D'Amato).

Background: There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19.

Methods: We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels.

Results: We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10) in the meta-analysis of the two case-control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P = 1.15×10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P = 4.95×10, respectively). At locus 3p21.31, the association signal spanned the genes , , , , and . The association signal at locus 9q34.2 coincided with the blood group locus; in this cohort, a blood-group-specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P = 1.48×10) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P = 1.06×10).

Conclusions: We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.).
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http://dx.doi.org/10.1056/NEJMoa2020283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315890PMC
October 2020

High mortality in COVID-19 patients with mild respiratory disease.

Eur J Clin Invest 2020 Sep 29;50(9):e13314. Epub 2020 Jun 29.

Humanitas Clinical and Research Center IRCCS, Rozzano, Italy.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 189 000 people in Italy, with more than 25 000 deaths. Several predictive factors of mortality have been identified; however, none has been validated in patients presenting with mild disease.

Methods: Patients with a diagnosis of interstitial pneumonia caused by SARS-CoV-2, presenting with mild symptoms, and requiring hospitalization in a non-intensive care unit with known discharge status were prospectively collected and retrospectively analysed. Demographical, clinical and biochemical parameters were recorded, as need for non-invasive mechanical ventilation and admission in intensive care unit. Univariate and multivariate logistic regression analyses were used to identify independent predictors of death.

Results: Between 28 February and 10 April 2020, 229 consecutive patients were included in the study cohort; the majority were males with a mean age of 60 years. 54% of patients had at least one comorbidity, with hypertension being the most commonly represented, followed by diabetes mellitus. 196 patients were discharged after a mean of 9 days, while 14.4% died during hospitalization because of respiratory failure. Age higher than 75 years, low platelet count (<150 × 10 /mm ) and higher ferritin levels (>750 ng/mL) were independent predictors of death. Comorbidities were not independently associated with in-hospital mortality.

Conclusions: In-hospital mortality of patients with COVID-19 presenting with mild symptoms is high and is associated with older age, platelet count and ferritin levels. Identifying early predictors of outcome can be useful in the clinical practice to better stratify and manage patients with COVID-19.
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http://dx.doi.org/10.1111/eci.13314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323076PMC
September 2020

Early Predictors of Clinical Deterioration in a Cohort of 239 Patients Hospitalized for Covid-19 Infection in Lombardy, Italy.

J Clin Med 2020 May 20;9(5). Epub 2020 May 20.

Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Milan, Italy.

We described features of hospitalized Covid-19 patients and identified predictors of clinical deterioration. We included patients consecutively admitted at Humanitas Research Hospital (Rozzano, Milan, Italy); retrospectively extracted demographic; clinical; laboratory and imaging findings at admission; used survival methods to identify factors associated with clinical deterioration (defined as intensive care unit (ICU) transfer or death), and developed a prognostic index. Overall; we analyzed 239 patients (29.3% females) with a mean age of 63.9 (standard deviation [SD]; 14.0) years. Clinical deterioration occurred in 70 patients (29.3%), including 41 (17.2%) ICU transfers and 36 (15.1%) deaths. The most common symptoms and signs at admission were cough (77.8%) and elevated respiratory rate (34.1%), while 66.5% of patients had at least one coexisting medical condition. Imaging frequently revealed ground-glass opacity (68.9%) and consolidation (23.8%). Age; increased respiratory rate; abnormal blood gas parameters and imaging findings; coexisting coronary heart disease; leukocytosis; lymphocytopenia; and several laboratory parameters (elevated procalcitonin; interleukin-6; serum ferritin; C-reactive protein; aspartate aminotransferase; lactate dehydrogenase; creatinine; fibrinogen; troponin-I; and D-dimer) were significant predictors of clinical deterioration. We suggested a prognostic index to assist risk-stratification (C-statistic; 0.845; 95% CI; 0.802‒0.887). These results could aid early identification and management of patients at risk, who should therefore receive additional monitoring and aggressive supportive care.
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http://dx.doi.org/10.3390/jcm9051548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290833PMC
May 2020

[Ultralow-contrast transcatheter aortic valve implantation with an Acurate neo prosthesis in a patient with severe chronic kidney disease].

G Ital Cardiol (Rome) 2020 04;21(4 Suppl 2):42S-45S

Dipartimento di Scienze Biomediche, Humanitas University, Pieve Emanuele (MI) - Dipartimento Cardiovascolare, IRCCS Istituto Clinico Humanitas, Rozzano (MI).

Chronic kidney disease patients undergoing transcatheter aortic valve implantation are at high risk of post-procedural acute kidney injury. In order to minimize this risk, a meticulous procedural planning is needed, as well as a multidisciplinary team of interventionalists and imaging specialists.We present the case of an ultralow contrast transcatheter aortic valve implantation with an Acurate neo self-expandable prosthesis in a patient with advanced chronic kidney disease.
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http://dx.doi.org/10.1714/3336.33073DOI Listing
April 2020

Advanced oxidation protein products in nondiabetic end stage renal disease patients on maintenance haemodialysis.

Free Radic Res 2019 Dec 22;53(11-12):1114-1124. Epub 2019 Nov 22.

Department of Biosciences (Department of Excellence 2018-2022), Università degli Studi di Milano, Milan, Italy.

In chronic kidney disease (CKD), the impairment of the excretory function leads to elevation in the blood concentrations of urea, creatinine, and various protein metabolic products. Advanced oxidation protein products (AOPP), along with protein carbonyls, protein-bound di-tyrosines and -thiolated proteins, are considered biomarkers of oxidative stress in end-stage renal disease (ESRD) patients on maintenance haemodialysis (HD). In this study, we evaluated the correlations between plasma levels of AOPP (measured by size exclusion/gel filtration high performance liquid chromatography) and those of protein-bound di-tyrosines, protein carbonyls, albumin and fibrinogen in 50 nondiabetic ESRD patients on maintenance HD. Considering that AOPP could represent the bridge between oxidative stress and inflammation, having been identified as proinflammatory mediators, we also evaluated the association between AOPP levels, C-reactive protein concentration and white blood cells count. Finally, we assessed the associations between plasma level of AOPP and serum concentrations of creatinine and urea, both of which showed a strong dependence on the chronological age of haemodialysed patients. Taken together, our results confirm the robust relationship between uraemia and oxidative stress, especially when measured as biomarkers of severe protein oxidative damage (e.g. plasma AOPP).
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http://dx.doi.org/10.1080/10715762.2019.1690651DOI Listing
December 2019

Slow life-history strategies are associated with negligible actuarial senescence in western Palaearctic salamanders.

Proc Biol Sci 2019 08 28;286(1909):20191498. Epub 2019 Aug 28.

Institut für Evolutionsbiologie und Umweltwissenschaften, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.

Actuarial senescence has been viewed for a long time as an inevitable and uniform process. However, the work on senescence has mainly focused on endotherms with deterministic growth and low regeneration capacity during the adult stage, leading to a strong taxonomic bias in the study of ageing. Recent studies have highlighted that senescence could indeed display highly variable trajectories that correlate with species life-history traits. Slow life histories and indeterminate growth seem to be associated with weak and late senescence. Furthermore, high regenerative abilities could lead to negligible senescence in ectotherms. However, demographic data for species that would allow testing of these hypotheses are scarce. Here, we investigated senescence patterns in 'true salamanders' from the western Palaearctic. Our results showed that salamanders have slow life histories and that they experience negligible senescence. This pattern was consistent at both intra- and interspecific levels, suggesting that the absence of senescence may be a phylogenetically conserved trait. The regenerative capacities of salamanders, in combination with other physiological and developmental features such as an indeterminate growth and a low metabolic rate, probably explain why these small ectotherms have lifespans similar to that of large endotherms and, in contrast with most amniotes, undergo negligible senescence. Our study seriously challenges the idea that senescence is a ubiquitous phenomenon in the tree of life.
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http://dx.doi.org/10.1098/rspb.2019.1498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732381PMC
August 2019

sp. nov. (Boletaceae), first report of a red-pored bolete from the Dominican Republic and insights on the genus .

MycoKeys 2019 29;49:73-97. Epub 2019 Mar 29.

Department of Life Sciences and Systems Biology, University of Turin, Viale P.A. Mattioli 25, I-10125 Torino, Italy.

appears to be the only red-pored bolete known from the Dominican Republic to date. It is reported as a novel species to science based on collections gathered in a neotropical lowland mixed broadleaved woodland. A detailed morphological description, color images of fresh basidiomes in habitat and line drawings of the main anatomical features are provided and relationships with phylogenetically and phenotypically similar taxa are discussed. Three genomic regions (nrITS, nrLSU/28S and ) have been sequenced in order to reinforce the recognition of the new species and to elucidate its taxonomic affiliation within .
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http://dx.doi.org/10.3897/mycokeys.49.33185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477853PMC
March 2019

Megaphylogeny resolves global patterns of mushroom evolution.

Nat Ecol Evol 2019 04 18;3(4):668-678. Epub 2019 Mar 18.

Synthetic and Systems Biology Unit, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.

Mushroom-forming fungi (Agaricomycetes) have the greatest morphological diversity and complexity of any group of fungi. They have radiated into most niches and fulfil diverse roles in the ecosystem, including wood decomposers, pathogens or mycorrhizal mutualists. Despite the importance of mushroom-forming fungi, large-scale patterns of their evolutionary history are poorly known, in part due to the lack of a comprehensive and dated molecular phylogeny. Here, using multigene and genome-based data, we assemble a 5,284-species phylogenetic tree and infer ages and broad patterns of speciation/extinction and morphological innovation in mushroom-forming fungi. Agaricomycetes started a rapid class-wide radiation in the Jurassic, coinciding with the spread of (sub)tropical coniferous forests and a warming climate. A possible mass extinction, several clade-specific adaptive radiations and morphological diversification of fruiting bodies followed during the Cretaceous and the Paleogene, convergently giving rise to the classic toadstool morphology, with a cap, stalk and gills (pileate-stipitate morphology). This morphology is associated with increased rates of lineage diversification, suggesting it represents a key innovation in the evolution of mushroom-forming fungi. The increase in mushroom diversity started during the Mesozoic-Cenozoic radiation event, an era of humid climate when terrestrial communities dominated by gymnosperms and reptiles were also expanding.
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http://dx.doi.org/10.1038/s41559-019-0834-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443077PMC
April 2019

Geriatric Nutritional Risk Index Is Predictive of Subjective Global Assessment and Dialysis Malnutrition Scores in Elderly Patients on Hemodialysis.

J Ren Nutr 2019 09 8;29(5):438-443. Epub 2019 Mar 8.

Division of Nephrology and Hemodialysis, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy.

Objective: Malnutrition is a frequent complication in patients on hemodialysis (HD), even if its adequate appraisal remains one of the most complicated challenges in the HD scenario because of the limits of current malnutrition biomarkers. The aim of our study was to assess the relation of subjective nutritional tools Subjective Global Assessment (SGA) and Dialysis Malnutrition Score (DMS) with the objective malnutrition tool Geriatric Nutritional Risk Index (GNRI) in elderly patients on HD.

Methods: This is a cross-sectional study involving 71 patients on maintenance HD. Mann-Whitney U and chi-square tests were used to compare data of male and female patients on HD. Linear and logistic regression models were used to assess the variables tested in all patients.

Results: GNRI was not different between male and female patients on HD, and it was negatively related to SGA and DMS: B, -0.05 (95% confidence interval, -0.08 to -0.02) P = 0.00 and B, -0.30 (95% confidence interval, -0.47 to -0.14) P = .00, respectively. Both continuous and categorical GNRI data were predictive of SGA = 3: Odds Ratio (OR), 0.74 (0.63 to 0.87) P = 0.00 and OR, 6.74 (1.54 to 29.45) P = 0.01, respectively. Similarly, GNRI data were related to DMS > 13: OR, 0.85 (0.76 to 0.85) P = 0.00 and 3.29 (1.08 to 10.05) P = 0.03, respectively. Continuous GNRI data remained significant in both male and female patients separately, whereas categorical GNRI data, only in male patients.

Conclusions: GNRI is a reliable nutritional tool predictive of subjective malnutrition scores SGA and DMS, pointing out a relation between objective and subjective malnutrition indexes in both genders.
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http://dx.doi.org/10.1053/j.jrn.2019.01.012DOI Listing
September 2019

High Animal and Vegetarian Protein Intake in Hemodialysis Patients.

J Ren Nutr 2019 05 8;29(3):248. Epub 2018 Oct 8.

Division of Nephrology and Hemodialysis, Humanitas Clinical and Research Hospital, Rozzano (MI), Italy.

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http://dx.doi.org/10.1053/j.jrn.2018.08.012DOI Listing
May 2019

Considerations and consequences of allowing DNA sequence data as types of fungal taxa.

Authors:
Juan Carlos Zamora Måns Svensson Roland Kirschner Ibai Olariaga Svengunnar Ryman Luis Alberto Parra József Geml Anna Rosling Slavomír Adamčík Teuvo Ahti M Catherine Aime A Martyn Ainsworth László Albert Edgardo Albertó Alberto Altés García Dmitry Ageev Reinhard Agerer Begoña Aguirre-Hudson Joe Ammirati Harry Andersson Claudio Angelini Vladimír Antonín Takayuki Aoki André Aptroot Didier Argaud Blanca Imelda Arguello Sosa Arne Aronsen Ulf Arup Bita Asgari Boris Assyov Violeta Atienza Ditte Bandini João Luís Baptista-Ferreira Hans-Otto Baral Tim Baroni Robert Weingart Barreto Henry Beker Ann Bell Jean-Michel Bellanger Francesco Bellù Martin Bemmann Mika Bendiksby Egil Bendiksen Katriina Bendiksen Lajos Benedek Anna Bérešová-Guttová Franz Berger Reinhard Berndt Annarosa Bernicchia Alona Yu Biketova Enrico Bizio Curtis Bjork Teun Boekhout David Boertmann Tanja Böhning Florent Boittin Carlos G Boluda Menno W Boomsluiter Jan Borovička Tor Erik Brandrud Uwe Braun Irwin Brodo Tatiana Bulyonkova Harold H Burdsall Bart Buyck Ana Rosa Burgaz Vicent Calatayud Philippe Callac Emanuele Campo Massimo Candusso Brigitte Capoen Joaquim Carbó Matteo Carbone Rafael F Castañeda-Ruiz Michael A Castellano Jie Chen Philippe Clerc Giovanni Consiglio Gilles Corriol Régis Courtecuisse Ana Crespo Cathy Cripps Pedro W Crous Gladstone Alves da Silva Meiriele da Silva Marjo Dam Nico Dam Frank Dämmrich Kanad Das Linda Davies Eske De Crop Andre De Kesel Ruben De Lange Bárbara De Madrignac Bonzi Thomas Edison E Dela Cruz Lynn Delgat Vincent Demoulin Dennis E Desjardin Paul Diederich Bálint Dima Maria Martha Dios Pradeep Kumar Divakar Clovis Douanla-Meli Brian Douglas Elisandro Ricardo Drechsler-Santos Paul S Dyer Ursula Eberhardt Damien Ertz Fernando Esteve-Raventós Javier Angel Etayo Salazar Vera Evenson Guillaume Eyssartier Edit Farkas Alain Favre Anna G Fedosova Mario Filippa Péter Finy Adam Flakus Simón Fos Jacques Fournier André Fraiture Paolo Franchi Ana Esperanza Franco Molano Gernot Friebes Andreas Frisch Alan Fryday Giuliana Furci Ricardo Galán Márquez Matteo Garbelotto Joaquina María García-Martín Mónica A García Otálora Dania García Sánchez Alain Gardiennet Sigisfredo Garnica Isaac Garrido Benavent Genevieve Gates Alice da Cruz Lima Gerlach Masoomeh Ghobad-Nejhad Tatiana B Gibertoni Tine Grebenc Irmgard Greilhuber Bella Grishkan Johannes Z Groenewald Martin Grube Gérald Gruhn Cécile Gueidan Gro Gulden Luis Fp Gusmão Josef Hafellner Michel Hairaud Marek Halama Nils Hallenberg Roy E Halling Karen Hansen Christoffer Bugge Harder Jacob Heilmann-Clausen Stip Helleman Alain Henriot Margarita Hernandez-Restrepo Raphaël Herve Caroline Hobart Mascha Hoffmeister Klaus Høiland Jan Holec Håkon Holien Karen Hughes Vit Hubka Seppo Huhtinen Boris Ivančević Marian Jagers Walter Jaklitsch AnnaElise Jansen Ruvishika S Jayawardena Thomas Stjernegaard Jeppesen Mikael Jeppson Peter Johnston Per Magnus Jørgensen Ingvar Kärnefelt Liudmila B Kalinina Gintaras Kantvilas Mitko Karadelev Taiga Kasuya Ivona Kautmanová Richard W Kerrigan Martin Kirchmair Anna Kiyashko Dániel G Knapp Henning Knudsen Kerry Knudsen Tommy Knutsson Miroslav Kolařík Urmas Kõljalg Alica Košuthová Attila Koszka Heikki Kotiranta Vera Kotkova Ondřej Koukol Jiří Kout Gábor M Kovács Martin Kříž Åsa Kruys Viktor Kučera Linas Kudzma Francisco Kuhar Martin Kukwa T K Arun Kumar Vladimír Kunca Ivana Kušan Thomas W Kuyper Carlos Lado Thomas Læssøe Patrice Lainé Ewald Langer Ellen Larsson Karl-Henrik Larsson Gary Laursen Christian Lechat Serena Lee James C Lendemer Laura Levin Uwe Lindemann Håkan Lindström Xingzhong Liu Regulo Carlos Llarena Hernandez Esteve Llop Csaba Locsmándi Deborah Jean Lodge Michael Loizides László Lőkös Jennifer Luangsa-Ard Matthias Lüderitz Thorsten Lumbsch Matthias Lutz Dan Mahoney Ekaterina Malysheva Vera Malysheva Patinjareveettil Manimohan Yasmina Marin-Felix Guilhermina Marques Rubén Martínez-Gil Guy Marson Gerardo Mata P Brandon Matheny Geir Harald Mathiassen Neven Matočec Helmut Mayrhofer Mehdi Mehrabi Ireneia Melo Armin Mešić Andrew S Methven Otto Miettinen Ana M Millanes Romero Andrew N Miller James K Mitchell Roland Moberg Pierre-Arthur Moreau Gabriel Moreno Olga Morozova Asunción Morte Lucia Muggia Guillermo Muñoz González Leena Myllys István Nagy László G Nagy Maria Alice Neves Tuomo Niemelä Pier Luigi Nimis Nicolas Niveiro Machiel E Noordeloos Anders Nordin Sara Raouia Noumeur Yuri Novozhilov Jorinde Nuytinck Esteri Ohenoja Patricia Oliveira Fiuza Alan Orange Alexander Ordynets Beatriz Ortiz-Santana Leticia Pacheco Ferenc Pál-Fám Melissa Palacio Zdeněk Palice Viktor Papp Kadri Pärtel Julia Pawlowska Aurelia Paz Ursula Peintner Shaun Pennycook Olinto Liparini Pereira Pablo Pérez Daniëls Miquel À Pérez-De-Gregorio Capella Carlos Manuel Pérez Del Amo Sergio Pérez Gorjón Sergio Pérez-Ortega Israel Pérez-Vargas Brian A Perry Jens H Petersen Ronald H Petersen Donald H Pfister Chayanard Phukhamsakda Marcin Piątek Meike Piepenbring Raquel Pino-Bodas Juan Pablo Pinzón Esquivel Paul Pirot Eugene S Popov Orlando Popoff María Prieto Álvaro Christian Printzen Nadezhda Psurtseva Witoon Purahong Luis Quijada Gerhard Rambold Natalia A Ramírez Huzefa Raja Olivier Raspé Tania Raymundo Martina Réblová Yury A Rebriev Juan de Dios Reyes García Miguel Ángel Ribes Ripoll Franck Richard Mike J Richardson Víctor J Rico Gerardo Lucio Robledo Flavia Rodrigues Barbosa Cristina Rodriguez-Caycedo Pamela Rodriguez-Flakus Anna Ronikier Luis Rubio Casas Katerina Rusevska Günter Saar Irja Saar Isabel Salcedo Sergio M Salcedo Martínez Carlos A Salvador Montoya Santiago Sánchez-Ramírez J Vladimir Sandoval-Sierra Sergi Santamaria Josiane Santana Monteiro Hans Josef Schroers Barbara Schulz Geert Schmidt-Stohn Trond Schumacher Beatrice Senn-Irlet Hana Ševčíková Oleg Shchepin Takashi Shirouzu Anton Shiryaev Klaus Siepe Esteban B Sir Mohammad Sohrabi Karl Soop Viacheslav Spirin Toby Spribille Marc Stadler Joost Stalpers Soili Stenroos Ave Suija Stellan Sunhede Sten Svantesson Sigvard Svensson Tatyana Yu Svetasheva Krzysztof Świerkosz Heidi Tamm Hatira Taskin Adrien Taudière Jan-Olof Tedebrand Raúl Tena Lahoz Marina Temina Arne Thell Marco Thines Göran Thor Holger Thüs Leif Tibell Sanja Tibell Einar Timdal Zdenko Tkalčec Tor Tønsberg Gérard Trichies Dagmar Triebel Andrei Tsurykau Rodham E Tulloss Veera Tuovinen Miguel Ulloa Sosa Carlos Urcelay François Valade Ricardo Valenzuela Garza Pieter van den Boom Nicolas Van Vooren Aida M Vasco-Palacios Jukka Vauras Juan Manuel Velasco Santos Else Vellinga Annemieke Verbeken Per Vetlesen Alfredo Vizzini Hermann Voglmayr Sergey Volobuev Wolfgang von Brackel Elena Voronina Grit Walther Roy Watling Evi Weber Mats Wedin Øyvind Weholt Martin Westberg Eugene Yurchenko Petr Zehnálek Huang Zhang Mikhail P Zhurbenko Stefan Ekman

IMA Fungus 2018 Jun 24;9(1):167-175. Epub 2018 May 24.

Museum of Evolution, Uppsala University, Norbyvägen 16, 75236 Uppsala, Sweden.

Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11 International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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http://dx.doi.org/10.5598/imafungus.2018.09.01.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048565PMC
June 2018

HCV-negative mixed cryoglobulinemia and kidney involvement: in-depth review on physiopathological and histological bases.

Clin Exp Med 2018 Nov 28;18(4):465-471. Epub 2018 Jun 28.

Unit of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.

Type II mixed cryoglobulinemia without evidence of HCV infection but rather with renal involvement has been occasionally described. The pathogenesis of cryoglobulinemic kidney disease is most likely related to immune complex deposition including cryoglobulins, and cryoaggregation after cold exposure could play a pivotal role in clinical expression of cryoglobulinemia. In these cases, acute kidney injury and proteinuria remain the most frequent clinical expression of a cryoglobulinemic glomerulonephritis. Type II cryoglobulinemia with the laboratory finding of both monoclonal and polyclonal cryoglobulins is the most prevalent bio-humoral pattern among HCV-negative phenotypes with renal involvement, while type III cryoglobulinemia with polyclonal Ig is rare. Histological data in renal biopsies support the hypothesis that regardless of the HCV status cryoglobulinemia vasculitis share the same frequent pathological finding of membranoproliferative glomerulonephritides, but other histological patterns have also been observed in a minority of cases. In HCV-negative mixed cryoglobulinaemia, the paraneoplastic origin of the immune dysfunction should be ruled out and sporadic cases have been reported, while there is no cumulative evidence on the prevalence of these tumour-associated manifestations. Moving from the classification criteria and the etiopathogenesis of mixed cryoglobulinaemia, we provide a comprehensive review of the literature on the appearance of the disease with kidney injury in association with malignancies or autoimmune disorders without HCV coexistence.
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http://dx.doi.org/10.1007/s10238-018-0514-5DOI Listing
November 2018

Subjective Global Assessment-Dialysis Malnutrition Score and cardiovascular risk in hemodialysis patients: an observational cohort study.

J Nephrol 2018 Oct 23;31(5):757-765. Epub 2018 Jun 23.

Electrophysiology and Cardiac Pacing Unit, Ospedale Civile di Mirano, via Luigi Mariutto 76, 30035, Mirano, VE, Italy.

Background: Malnutrition is an important risk factor for cardiovascular mortality in hemodialysis (HD) patients. However, current malnutrition biomarkers seem unable to accurately estimate the role of malnutrition in predicting cardiovascular risk. Our aim was to investigate the role of the Subjective Global Assessment-Dialysis Malnutrition Score (SGA-DMS) compared to two well-recognized comorbidity scores-Charlson Comorbidity Index (CCI) and modified CCI (excluding age-factor) (mCCI)-in predicting cardiovascular events in HD patients.

Methods: In 86 maintenance HD patients followed from June 2015 to June 2017, we analyzed biohumoral data and clinical scores as risk factors for cardiovascular events (acute heart failure, acute coronary syndrome and stroke). Their impact on outcome was investigated by linear regression, Cox regression models and ROC analysis.

Results: Cardiovascular events occurred in 26/86 (30%) patients during the 2-year follow-up. Linear regression showed only age and dialysis vintage to be positively related to SGA-DMS: B 0.21 (95% CI 0.01; 0.30) p 0.05, and B 0.24 (0.09; 0.34) p 0.02, respectively, while serum albumin, normalized protein catabolic rate (nPCR) and dialysis dose (Kt/V) were negatively related to SGA-DMS: B - 1.29 (- 3.29; - 0.81) p 0.02; B - 0.08 (- 1.52; - 0.35) p 0.04 and B - 2.63 (- 5.25; - 0.22) p 0.03, respectively. At Cox regression analysis, SGA-DMS was not a risk predictor for cardiovascular events: HR 1.09 (0.9; 1.22), while both CCI and mCCI were significant predictors: HR 1.43 (1.13; 1.87) and HR 1.57 (1.20; 2.06) also in Cox adjusted models. ROC analysis reported similar AUCs for CCI and mCCI: 0.72 (0.60; 0.89) p 0.00 and 0.70 (0.58; 0.82) p 0.00, respectively, compared to SGA-DMS 0.56 (0.49; 0.72) p 0.14.

Conclusions: SGA-DMS is not a superior and significant prognostic tool compared to CCI and mCCI in assessing cardiovascular risk in HD patients, even it allows to appraise both malnutrition and comorbidity status.
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http://dx.doi.org/10.1007/s40620-018-0505-3DOI Listing
October 2018

Subjective Global Assessment-Dialysis Malnutrition Score and arteriovenous fistula outcome: A comparison with Charlson Comorbidity Index.

J Vasc Access 2019 Jan 7;20(1):70-78. Epub 2018 Jun 7.

1 Humanitas, Clinical and Research Center, Renal and Hemodialysis Unit, Rozzano (MI), Italy.

Introduction:: Malnutrition is a well-recognized risk factor for all-cause mortality in hemodialysis patients. However, its role for arteriovenous fistulas outcome has not been exhaustively investigated. Our aim was to point out the impact of Subjective Global Assessment-Dialysis Malnutrition Score as independent predictor of arteriovenous fistulas thrombosis (vascular access thrombosis) and/or significant stenosis (vascular access stenosis). In addition, we compared it with the widespread Charlson Comorbidity Index.

Methods:: We assessed 57 hemodialysis patients for a 2-year interval and evaluated the incidence of vascular access thrombosis and/or stenosis. Linear regression analysis was used to test the relation of variables with Subjective Global Assessment-Dialysis Malnutrition Score at baseline. Logistic and Cox regression analysis evaluated markers as predictors of both vascular access thrombosis and stenosis. Receiver operating characteristic curve analysis was used to compare area under the curve values of Subjective Global Assessment-Dialysis Malnutrition Score, Charlson Comorbidity Index, and modified Charlson Comorbidity Index.

Results:: Age and Charlson Comorbidity Index were positively related to Subjective Global Assessment-Dialysis Malnutrition Score: B = 0.06 (95% CI = 0.01; 0.11) and B = 0.31 (95% CI = 0.01; 0.63). Higher albumin and normalized protein catabolic rate levels had a protective role against vascular access failure: OR = 0.67 (95% CI = 0.56; 0.81) and OR = 0.46 (95% CI = 0.32; 0.67), respectively. Higher Subjective Global Assessment-Dialysis Malnutrition Score and Charlson Comorbidity Index values were significant risk factors: HR = 1.42 (95% CI = 1.04; 1.92) and HR = 1.48 (95% CI = 1.01; 2.17), respectively. Area under the curve of Subjective Global Assessment-Dialysis Malnutrition Score was significantly higher than those of both Charlson Comorbidity Index and modified Charlson Comorbidity Index: 0.70 (95% CI = 0.50; 0.88) versus 0.61 (95% CI = 0.41; 0.80) and 0.55 (95CI% = 0.41; 0.70).

Conclusion:: Subjective Global Assessment-Dialysis Malnutrition Score, as well as Charlson Comorbidity Index, are useful tools to predict vascular access failure and should be carefully and periodically evaluated in order to check significant variations that may compromise vascular access survival.
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http://dx.doi.org/10.1177/1129729818779550DOI Listing
January 2019

Diversity of polypores in the Dominican Republic: sp. nov. (Hericiaceae, Russulales).

MycoKeys 2018 16(34):35-45. Epub 2018 May 16.

Department of Life Sciences and Systems Biology, University of Torino, Viale P.A. Mattioli 25, I-10125, Torino, Italy.

The new species is described from the Dominican Republic based on morphological and molecular data (nrITS and nrLSU sequence analyses). It is mainly characterised by pileate basidiomata with a bright pinkish context and a di-trimitic hyphal system. Phylogenetically, it is sister to the African species and to the Asiatic .
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http://dx.doi.org/10.3897/mycokeys.34.25371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966507PMC
May 2018

SGLT1 and SGLT1 Inhibitors: A Role to Be Assessed in the Current Clinical Practice.

Diabetes Ther 2018 Feb 24;9(1):427-430. Epub 2017 Nov 24.

Division of Nephrology and Hemodialysis, Humanitas Clinical and Research Center, Milan, Italy.

Diabetes is a complex disease of increasingly common occurrence worldwide. Attaining optimal glycemic control is the main challenge to prevent the development of diabetes-related complications and/or to stop their progression. In recent years, the pharmacologic toolkit for the treatment of diabetes has considerably expanded, thus paving the way to more pathophysiology-oriented therapies. For instance, the sodium-glucose cotransporters SGLT2 and SGLT1 have been in the spotlight because of better knowledge of their physiology and therapeutic potential. At present, whereas the SGLT2 inhibitors are widely applied in current clinical practice as an effective and well-tolerated treatment that increases the urinary excretion of glucose, less is known about the use of SGLT1 inhibitors. SGLT1s are of primary importance in the small intestine, an organ that does not express SGLT2, while in the kidney they are expressed in the late renal proximal tubules, where it reabsorbs the glucose escaped from the upstream SGLT2. Hence, SGLT1-mediated glucose reabsorption in the kidney is increased when the tubular glucose load overwhelms the capacity of SGLT2 or when the latter is inhibited. The role of SGLT1 in intestinal and renal glucose transport makes the transporter a potential target for antidiabetic therapy. Here, we briefly report the evidence on LX2761, a new inhibitor against SGLT1 and SGLT2 in vitro, which acts in vivo as a selective inhibitor of SGLT1 in the gastrointestinal tract. LX2761 improves glycemic control without the glycosuria-related side effects of SGLT2 inhibitors, particularly genitourinary tract infections. However, whether it represents a valid therapeutic option for all patients with diabetes or is more appropriate for specific phenotypes, e.g., patients with concomitant diabetes and chronic kidney disease, who may benefit less from the renal mechanism of selective SGLT2 inhibitors, remains to be tested in large randomized controlled trials.
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http://dx.doi.org/10.1007/s13300-017-0342-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801228PMC
February 2018

Evaluation of Endothelial Function by Flow-Mediated Dilation: a Comprehensive Review in Rheumatic Disease.

Arch Immunol Ther Exp (Warsz) 2017 Dec 30;65(6):463-475. Epub 2017 Mar 30.

University of Milan, Milan, Italy.

Flow-mediated dilation (FMD) represents a non-invasive marker of endothelial function to evaluate vascular homeostasis, which reflects the effects of several mechanisms, including vessel tone regulation, cell proliferation, and inflammatory responses. Beyond classical atherosclerotic risk factors such as arterial hypertension, diabetes mellitus, smoking, obesity, and dyslipidemia, chronic inflammation contributes to the endothelial dysfunction causing plaque formation and there is growing evidence of a significantly higher cardiovascular morbidity associated with autoimmune diseases. The endothelium reacts to several endogenous and exogenous stimuli, through surface receptors and intracellular signalling, and releases numerous vasoactive substances, including endothelins, prostacyclins, and nitric oxide (NO). Chronic inflammatory rheumatic diseases are commonly associated with decreased endothelial NO production, vascular damage, and premature atherosclerosis. Despite partially eclipsed by pulse wave velocity measure in the modern scientific literature, we provide a comprehensive overview and critically discuss the available data supporting FMD as a surrogate marker of endothelial function and, therefore, its potential role in predicting early atherosclerosis in patients with rheumatic diseases.
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http://dx.doi.org/10.1007/s00005-017-0465-7DOI Listing
December 2017

Islands within an island: Population genetic structure of the endemic Sardinian newt, .

Ecol Evol 2017 02 25;7(4):1190-1211. Epub 2017 Jan 25.

Institute of ZoologyThe Zoological Society of London London UK; Zirichiltaggi S. W. C. Non-profit Association for Wildlife Conservation Sassari Italy.

The identification of historic and contemporary barriers to dispersal is central to the conservation of endangered amphibians, but may be hindered by their complex life history and elusive nature. The complementary information generated by mitochondrial (mtDNA) and microsatellite markers generates a valuable tool in elucidating population structure and the impact of habitat fragmentation. We applied this approach to the study of an endangered montane newt, . Endemic to the Mediterranean island of Sardinia, it is threatened by anthropogenic activity, disease, and climate change. We have demonstrated a clear hierarchy of structure across genetically divergent and spatially distinct subpopulations. Divergence between three main mountain regions dominated genetic partitioning with both markers. Mitochondrial phylogeography revealed a deep division dating to ca. 1 million years ago (Mya), isolating the northern region, and further differentiation between the central and southern regions ca. 0.5 Mya, suggesting an association with Pleistocene severe glacial oscillations. Our findings are consistent with a model of southward range expansion during glacial periods, with postglacial range retraction to montane habitat and subsequent genetic isolation. Microsatellite markers revealed further strong population structure, demonstrating significant divergence within the central region, and partial differentiation within the south. The northern population showed reduced genetic diversity. Discordance between mitochondrial and microsatellite markers at this scale indicated a further complexity of population structure, in keeping with male-biased dispersal and female philopatry. Our study underscores the need to elucidate cryptic population structure in the ecology and conservation strategies for endangered island-restricted amphibians, especially in the context of disease and climate change.
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http://dx.doi.org/10.1002/ece3.2665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306002PMC
February 2017

Kidney stones diseases and glycaemic statuses: focus on the latest clinical evidences.

Urolithiasis 2017 Oct 5;45(5):457-460. Epub 2016 Dec 5.

Division of Nephrology, Policlinico Universitario "Agostino Gemelli", Largo Agostino Gemelli 8, 00168, Rome, RM, Italy.

Diabetes and obesity are already recognized as potential risk factors for nephrolithiasis, especially for uric acid stones. Insulin resistance and hyperinsulinemia actively contribute to impaired ability to excrete an acid load and altered ammonium production, leading to a lower urinary pH compared to non-diabetic controls. All these electrolytic disorders play an important role in stone formation and aggregation, especially in uric acid stones. There are still missing points in scientific evidence if the increased risk in stone formation is already existing even in the prediabetic statuses (isolated impaired glucose tolerance, isolated impaired fasting glucose, and associated impaired glucose tolerance/impaired fasting glucose) as well as it is worth to consider the same level of risk. Urolithiasis is the most frequent urological cause of hospitalization in diabetic patients and its cost is usually higher compared to non-diabetic patients, but less is known in others altered glycaemic diseases. The aim of this review article is to focus on the association between stone formation and altered glycaemic statuses, beyond the already known link between nephrolithiasis and diabetes mellitus.
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http://dx.doi.org/10.1007/s00240-016-0956-8DOI Listing
October 2017

Expression and function of IL-1R8 (TIR8/SIGIRR): a regulatory member of the IL-1 receptor family in platelets.

Cardiovasc Res 2016 09 13;111(4):373-84. Epub 2016 Jun 13.

Laboratory of Experimental Immunopathology, Humanitas Clinical and Research Center, via Manzoni 113, 20089 Rozzano, Italy

Aims: Platelets express functional interleukin-1 receptor-1 (IL-1R1) as well as a repertoire of toll-like receptors (TLRs) involved in platelet activation, platelet-leucocyte reciprocal activation, and immunopathology. IL-1R8, also known as single Ig IL-1-related receptor (SIGIRR) or TIR8, is a member of the IL-1R family that negatively regulates responses to IL-1R family members and TLRs. In the present study, we addressed the expression of IL-1R8 in platelets and megakaryocytes and its role in the control of platelet activation during inflammatory conditions and thromboembolism.

Methods And Results: Here, we show by flow cytometry analysis, western blot, confocal microscopy, and quantitative real-time polymerase chain reaction that IL-1R8 is expressed on human and mouse platelets at high levels and on megakaryocytes. IL-1R8-deficient mice show normal levels of circulating platelets. Homotypic and heterotypic (platelet-neutrophil) aggregation triggered by Adenosine DiPhosphate (ADP) and IL-1 or lipopolysaccharide (LPS) was increased in IL-1R8-deficient platelets. IL-1R8-deficient mice showed increased soluble P-selectin levels and increased platelet-neutrophil aggregates after systemic LPS administration. Commensal flora depletion and IL-1R1 deficiency abated platelet hyperactivity and the increased platelet/neutrophil aggregation observed in Il1r8(-/-) mice in vitro and in vivo, suggesting a key role of IL-1R8 in regulating platelet TLR and IL-1R1 function. In a mouse model of platelet-dependent pulmonary thromboembolism induced by ADP administration, IL-1R8-deficient mice showed an increased frequency of blood vessel complete obstruction.

Conclusion: These results show that platelets, which have a large repertoire of TLRs and IL-1 receptors, express high levels of IL-1R8, which plays a non-redundant function as a regulator of thrombocyte activity in vitro and in vivo.
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http://dx.doi.org/10.1093/cvr/cvw162DOI Listing
September 2016