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Article ; Online: TOSCA: an automated Tumor Only Somatic CAlling workflow for somatic mutation detection without matched normal samples.

Del Corvo, Marcello / Mazzara, Saveria / Pileri, Stefano A

Bioinformatics advances

2022 Volume 2, Issue 1, Page(s) vbac070

Abstract: Motivation: Accurate classification of somatic variants in a tumor sample is often accomplished by utilizing a paired normal tissue sample from the same patient to enable the separation of private germline mutations from somatic variants. However, a ... ...

Abstract	Motivation: Accurate classification of somatic variants in a tumor sample is often accomplished by utilizing a paired normal tissue sample from the same patient to enable the separation of private germline mutations from somatic variants. However, a paired normal sample is not always available, making a reliable somatic variant calling more challenging. Results: To address these limitations, we developed TOSCA, the first automated tumor-only somatic calling workflow in whole-exome sequencing and targeted panel sequencing data which performs an end-to-end analysis from raw read files, via quality checks, alignment and variant calling to functional annotation, databases filtering, tumor purity and ploidy estimation and variant classification. Application of our workflow to tumor-only data provides estimates of somatic and germline variants that are consistent with results from paired analyses. Availability and implementation: TOSCA is a Snakemake-based workflow and freely available at https://github.com/mdelcorvo/TOSCA. Supplementary information: Supplementary data are available at
Language	English
Publishing date	2022-09-26
Publishing country	England
Document type	Journal Article
ISSN	2635-0041
ISSN (online)	2635-0041
DOI	10.1093/bioadv/vbac070
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Article ; Online: Formulation of spray dried enzymes for dry powder inhalers: An integrated methodology.

Fernandes, Diana A / Costa, Eunice / Leandro, Paula / Corvo, M Luísa

International journal of pharmaceutics

2022 Volume 615, Page(s) 121492

Abstract: One of the main challenges when developing a spray dried formulation of an inhalable enzyme is the generation of a safe and effective aerosol, able to reach the lungs, while preserving protein function and structural levels of the biologic. Hence, an ... ...

Abstract	One of the main challenges when developing a spray dried formulation of an inhalable enzyme is the generation of a safe and effective aerosol, able to reach the lungs, while preserving protein function and structural levels of the biologic. Hence, an appropriate excipient selection based on enzyme stabilization, inhalation precedence and spray drying (SD) process development is required to meet this balance. Herein, an integrated methodology is presented to expedite the selection of the best dry powder inhaler excipient system to formulate three model enzymes of increasing molecular mass and structural complexity belonging to the oxidoreductase class and often implicated in oxidative stress: superoxide dismutase, glucose oxidase and catalase. Three non-reducing sugars and four amino acids were screened using High Throughput Isothermal Denaturation Fluorimetry (HT-ITDF) for a stabilizing effect on the enzymes quaternary structure. For each tested enzyme, the sugar and amino acid showcasing a stabilizing effect, were spray dried together at fixed process conditions for three different ratios, to assess which formulation would then display the best aerodynamic performance. After SD, using the selected conditions, all powders displayed 65-85% of fine particle fraction (FPF) whilst each enzyme kept the oligomeric state. The present integrated methodology proved to be successful, allowing to narrow down 36 potential formulations (three sugars × four amino acids × three ratios) to only one for each enzyme, within few hours, while requiring a μg range of sample amount.
Language	English
Publishing date	2022-01-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2022.121492
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Article ; Online: Optimization and Validation of an In Vitro Standardized Glycogen Phosphorylase Activity Assay.

Rocha, Sónia / Lucas, Mariana / Araújo, Alberto N / Corvo, M Luísa / Fernandes, Eduarda / Freitas, Marisa

Molecules (Basel, Switzerland)

2021 Volume 26, Issue 15

Abstract: Glycogen phosphorylase (GP) is a key enzyme in the glycogenolysis pathway and a potential therapeutic target in the management of type 2 diabetes. It catalyzes a reversible reaction: the release of the terminal glucosyl residue from glycogen as glucose 1- ...

Abstract	Glycogen phosphorylase (GP) is a key enzyme in the glycogenolysis pathway and a potential therapeutic target in the management of type 2 diabetes. It catalyzes a reversible reaction: the release of the terminal glucosyl residue from glycogen as glucose 1-phosphate; or the transfer of glucose from glucose 1-phosphate to glycogen. A colorimetric method to follow in vitro the activity of GP with usefulness in structure-activity relationship studies and high-throughput screening capability is herein described. The obtained results allowed the choice of the optimal concentration of enzyme of 0.38 U/mL, 0.25 mM glucose 1-phosphate, 0.25 mg/mL glycogen, and temperature of 37 °C. Three known GP inhibitors, CP-91149, a synthetic inhibitor, caffeine, an alkaloid, and ellagic acid, a polyphenol, were used to validate the method, CP-91149 being the most active inhibitor. The effect of glucose on the IC
MeSH term(s)	Amides/pharmacology ; Animals ; Caffeine/pharmacology ; Ellagic Acid/pharmacology ; Enzyme Assays ; Glucose/chemistry ; Glucosephosphates/chemistry ; Glycogen/chemistry ; Glycogen Phosphorylase/antagonists & inhibitors ; Glycogen Phosphorylase/chemistry ; Glycogen Phosphorylase/isolation & purification ; High-Throughput Screening Assays ; Indoles/pharmacology ; Kinetics ; Rabbits ; Solutions ; Structure-Activity Relationship
Chemical Substances	Amides ; CP 91149 ; Glucosephosphates ; Indoles ; Solutions ; Ellagic Acid (19YRN3ZS9P) ; Caffeine (3G6A5W338E) ; Glycogen (9005-79-2) ; glucose-1-phosphate (CIX3U01VAU) ; Glycogen Phosphorylase (EC 2.4.1.-) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-07-30
Publishing country	Switzerland
Document type	Journal Article ; Validation Study
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules26154635
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Article ; Online: Nano-based drug delivery systems used as vehicles to enhance polyphenols therapeutic effect for diabetes mellitus treatment.

Rocha, Sónia / Lucas, Mariana / Ribeiro, Daniela / Corvo, M Luísa / Fernandes, Eduarda / Freitas, Marisa

Pharmacological research

2021 Volume 169, Page(s) 105604

Abstract: Diabetes mellitus is one of the biggest health emergencies of the ... ...

Abstract	Diabetes mellitus is one of the biggest health emergencies of the 21
MeSH term(s)	Animals ; Diabetes Mellitus, Type 1/drug therapy ; Humans ; Hypoglycemic Agents/administration & dosage ; Hypoglycemic Agents/therapeutic use ; Nanoparticle Drug Delivery System/administration & dosage
Chemical Substances	Hypoglycemic Agents ; Nanoparticle Drug Delivery System
Language	English
Publishing date	2021-05-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2021.105604
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Zs.A 721: Show issues

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Article ; Online: Dry powder inhaler formulation comparison: Study of the role of particle deposition pattern and dissolution.

Noriega-Fernandes, Beatriz / Malmlöf, Maria / Nowenwik, Mattias / Gerde, Per / Corvo, M Luisa / Costa, Eunice

International journal of pharmaceutics

2021 Volume 607, Page(s) 121025

Abstract: The composition, morphology and dissolution profile of particles and micro-sized agglomerates delivered upon inhalation may have a significant impact on the product clinical effect. However, although several efforts are ongoing, a methodology that ... ...

Abstract	The composition, morphology and dissolution profile of particles and micro-sized agglomerates delivered upon inhalation may have a significant impact on the product clinical effect. However, although several efforts are ongoing, a methodology that considers deposition structures and dissolution performance evaluation in a biorelevant set-up is not yet standardized. The goal of this work is to apply a collection and dissolution methodology able to discriminate dry powder inhaler (DPI) formulations in terms of deposition structures and dissolution profile in vitro. Hence, Fluticasone Propionate (FP) engineered particles and formulated products (used as a case study) were collected employing a breath simulator and characterized regarding (i) aerodynamic particle size distribution; (ii) deposited microstructures; and (iii) dissolution/absorption profiles using the DissolvIt® bio-relevant dissolution equipment. The results indicated that the particle engineering technology had an impact on the generated and deposited microstructures, here associated to the differences on surface properties of jet milled and wet polished particles quantified by the specific surface area. Differences on surface properties modulate particle interactions, resulting in agglomerates of drug substance and excipient upon actuation with significant different morphologies, observed by microscope, as well as quantified by Marple cascade impactor. These observations allow for a further understanding of the DPI aerosolization and deposition mechanisms. The dissolution and absorption assessment indicates that the presence of lactose may accelerate the drug substance dissolution kinetics, and the FP dissolution can be significantly enhanced when formulated as a spray-dried dispersion particle. Ultimately, the results suggest dissolution testing can be an essential tool to both optimize an innovator DPI and de-risk generics development.
MeSH term(s)	Administration, Inhalation ; Aerosols ; Dry Powder Inhalers ; Particle Size ; Powders ; Solubility
Chemical Substances	Aerosols ; Powders
Language	English
Publishing date	2021-08-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2021.121025
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Zs.A 1409: Show issues

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Article ; Online: Maternal undernutrition during periconceptional period affects whole-genome ovine muscle methylation in adult offspring.

Capra, Emanuele / Toschi, Paola / Del Corvo, Marcello / Lazzari, Barbara / Stella, Alessandra / Williams, John Lewis / Loi, Pasqualino / Ajmone Marsan, Paolo

Journal of animal science

2022 Volume 100, Issue 8

Abstract: Experimental and epidemiological studies suggest that maternal nutritional status during early pregnancy, including the period around the time of conception, may induce long-lasting epigenetic changes in the offspring. However, this remains largely ... ...

Abstract	Experimental and epidemiological studies suggest that maternal nutritional status during early pregnancy, including the period around the time of conception, may induce long-lasting epigenetic changes in the offspring. However, this remains largely unexplored in livestock. Therefore, the objective of this study was to evaluate if modification of the maternal diet of sheep (CTR: control; UND: 50% undernutrition) during the periconceptional period (42 d in total: -14/+28 from mating), would impact CpG methylation in muscle tissue (Longissimus dorsi) of adult offspring (11.5 mo old). Reduced representation bisulfite sequencing identified 262 (Edge-R, FDR < 0.05) and 686 (logistic regression, FDR < 0.001) differentially methylated regions (DMRs) between the UND and CTR groups. Gene ontology analysis identified genes related to development, functions of the muscular system, and steroid hormone receptor activity within the DMRs. The data reported here show that nutritional stress during early pregnancy leads to epigenetic modifications in the muscle of the resulting offspring, with possible implications for cardiac dysfunction, muscle physiology, and meat production.
MeSH term(s)	Animals ; DNA Methylation ; Epigenesis, Genetic ; Female ; Malnutrition/veterinary ; Maternal Nutritional Physiological Phenomena ; Maternal-Fetal Exchange ; Muscles ; Pregnancy ; Sheep ; Sheep Diseases
Language	English
Publishing date	2022-05-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	390959-1
ISSN	1525-3163 ; 0021-8812
ISSN (online)	1525-3163
ISSN	0021-8812
DOI	10.1093/jas/skac180
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Zs.A 1312: Show issues

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Article: Approccio in Pronto Soccorso al bambino con emorragia gastroenterica.

Corvo, M / Valladè, A

La Pediatria medica e chirurgica : Medical and surgical pediatrics

2008 Volume 30, Issue 6, Page(s) 290–295

Abstract: Gastrointestinal bleeding may present with haematemesis, fresh rectal bleeding, melaena, abdominal pain, syncope and shock. Most patients require observation and no treatment. The majority of those requiring treatment stop bleeding spontaneously and the ... ...

Title translation	Approach in First Aid to children with gastrointestinal hemorrhage.
Abstract	Gastrointestinal bleeding may present with haematemesis, fresh rectal bleeding, melaena, abdominal pain, syncope and shock. Most patients require observation and no treatment. The majority of those requiring treatment stop bleeding spontaneously and the management is supportive. More aggressive investigation and treatment are required for persistent massive bleeding. Large bleeds require rapid volume replacement using saline or plasma, with blood transfusion as urgently as possible.
MeSH term(s)	Adolescent ; Age Factors ; Blood Transfusion ; Child ; Child, Preschool ; Diagnosis, Differential ; First Aid ; Gastrointestinal Hemorrhage/diagnosis ; Gastrointestinal Hemorrhage/diagnostic imaging ; Gastrointestinal Hemorrhage/etiology ; Gastrointestinal Hemorrhage/mortality ; Gastrointestinal Hemorrhage/surgery ; Gastrointestinal Hemorrhage/therapy ; Hematemesis/diagnosis ; Hematemesis/etiology ; Hematemesis/therapy ; Humans ; Infant ; Infant, Newborn ; Melena/diagnosis ; Melena/etiology ; Melena/therapy ; Physical Examination ; Plasma Substitutes/administration & dosage ; Radiography, Abdominal
Chemical Substances	Plasma Substitutes
Language	Italian
Publishing date	2008-11
Publishing country	Italy
Document type	Comparative Study ; Journal Article ; Review
ZDB-ID	605942-9
ISSN	2420-7748 ; 0391-5387
ISSN (online)	2420-7748
ISSN	0391-5387
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Zs.A 2022: Show issues

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Article ; Online: A Microenvironment-Related Nine-Gene Signature May Predict Survival in Mycosis Fungoides Patients at Diagnosis.

Alberti-Violetti, Silvia / Sapienza, Maria Rosaria / Del Corvo, Marcello / Melle, Federica / Motta, Giovanna / Venegoni, Luigia / Cerroni, Lorenzo / Cota, Carlo / Pileri, Alessandro / Berti, Emilio / Pileri, Stefano A

Cells

2023 Volume 12, Issue 15

Abstract: Mycosis fungoides (MF) is the most common cutaneous lymphoma characterized by an indolent course. Prognosis is stage-based but this approach does not reflect the different outcomes within stages. Considering that tumor microenvironment is known to be ... ...

Abstract	Mycosis fungoides (MF) is the most common cutaneous lymphoma characterized by an indolent course. Prognosis is stage-based but this approach does not reflect the different outcomes within stages. Considering that tumor microenvironment is known to be involved in MF pathogenesis and progression, we decided to investigate 99 MF cases by using the PanCancer Immune Profiling Panel. We identified and validated a signature of 9 genes able to predict MF survival and distinguish a high-risk group with a worse outcome from a low-risk group of cases with a better outcome. At the molecular level, low-risk vs. high-risk cases reported a global upregulation of immune genes, enriched in cytokines, and a higher density of dendritic cells and mast cells, possibly associated with a more favorable clinical course.
MeSH term(s)	Humans ; Mycosis Fungoides/diagnosis ; Mycosis Fungoides/genetics ; Lymphoma, T-Cell, Cutaneous/genetics ; Skin Neoplasms/diagnosis ; Skin Neoplasms/genetics ; Skin Neoplasms/pathology ; Risk Factors ; Lymphoma, Non-Hodgkin ; Tumor Microenvironment/genetics
Language	English
Publishing date	2023-07-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12151944
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Article: Assessing the role of membrane lipids in the action of ruthenium(III) anticancer compounds.

Starosta, Radoslaw / Santos, Telma C / Dinis de Sousa, Andreia F / Santos, Maria Soledade / Corvo, M Luisa / Tomaz, Ana Isabel / de Almeida, Rodrigo F M

Frontiers in molecular biosciences

2023 Volume 9, Page(s) 1059116

Abstract: This work addresses the possible role of the cell membrane in the molecular mechanism of action of ... ...

Abstract	This work addresses the possible role of the cell membrane in the molecular mechanism of action of two
Language	English
Publishing date	2023-01-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2022.1059116
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Article ; Online: Selection with inbreeding control in simulated young bull schemes for local dairy cattle breeds.

Gandini, G / Stella, A / Del Corvo, M / Jansen, G B

Journal of dairy science

2014 Volume 97, Issue 3, Page(s) 1790–1798

Abstract: Local breeds are rarely subject to modern selection techniques; however, selection programs will be required if local breeds are to remain a viable livelihood option for farmers. Selection in small populations needs to take into account accurate ... ...

Abstract	Local breeds are rarely subject to modern selection techniques; however, selection programs will be required if local breeds are to remain a viable livelihood option for farmers. Selection in small populations needs to take into account accurate inbreeding control. Optimum contribution selection (OCS) is efficient in controlling inbreeding and maximizes genetic gain. The current paper investigates genetic progress in simulated dairy cattle populations from 500 to 6,000 cows undergoing young bull selection schemes with OCS compared with truncation selection (TS) at an annual inbreeding rate of 0.003. Selection is carried out for a dairy trait with a base heritability of 0.3. A young bull selection scheme was used because of its simplicity in implementation. With TS, annual genetic gain from 0.111 standard deviation units with 500 cows increases rapidly to 0.145 standard deviation units with 4,000 cows. Then, genetic gain increases more slowly up to 6,000 cows. At the same inbreeding rate, OCS produces higher genetic progress than TS. Differences in genetic gain between OCS and TS vary from to 2 to 6.3%. Genetic gain is also improved by increasing the number of years that males can be used as sires of sires. When comparing OCS versus TS at different heritabilities, we observe an advantage of OCS only at high heritability, up to 8% with heritability of 0.9. By increasing the constraint on inbreeding, the difference of genetic gain between the 2 selection methods increases in favor of OCS, and the advantage at the inbreeding rate of 0.001 per generation is 6 times more than at the inbreeding rate of 0.003. Opportunities exist for selection even in dairy cattle populations of a few hundred females. In any case, selection in local breeds will most often require specific investments in infrastructure and manpower, including systems for accurate data recording and selection skills and the presence of artificial insemination and breeders organizations. A cost-benefit analysis is therefore advisable before considering the implementation of selection schemes in local dairy cattle breeds.
MeSH term(s)	Animals ; Cattle/genetics ; Dairying/methods ; Inbreeding ; Male ; Models, Genetic ; Selection, Genetic
Language	English
Publishing date	2014-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	242499-x
ISSN	1525-3198 ; 0022-0302
ISSN (online)	1525-3198
ISSN	0022-0302
DOI	10.3168/jds.2013-7184
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