@article{Piperni2024-av,

title = {Intestinal Blastocystis is linked to healthier diets and more  favorable cardiometabolic outcomes in 56,989 individuals from 32  countries},

author = {Elisa Piperni and Long H Nguyen and Paolo Manghi and Hanseul Kim and Edoardo Pasolli and Sergio Andreu-Sánchez and Alberto Arr`e and Kate M Bermingham and Aitor Blanco-M'iguez and Serena Manara and Mireia Valles-Colomer and Elco Bakker and Fabio Busonero and Richard Davies and Edoardo Fiorillo and Francesca Giordano and George Hadjigeorgiou and Emily R Leeming and Monia Lobina and Marco Masala and Andrea Maschio and Lauren J McIver and Mauro Pala and Maristella Pitzalis and Jonathan Wolf and Jingyuan Fu and Alexandra Zhernakova and Simone M Cacci`o and Francesco Cucca and Sarah E Berry and Danilo Ercolini and Andrew T Chan and Curtis Huttenhower and Tim D Spector and Nicola Segata and Francesco Asnicar},

doi = {10.1016/j.cell.2024.06.018},

year  = {2024},

date = {2024-08-01},

urldate = {2024-08-01},

journal = {Cell},

volume = {187},

number = {17},

pages = {4554--4570.e18},

publisher = {Elsevier BV},

abstract = {Diet impacts human health, influencing body adiposity and the 

 risk of developing cardiometabolic diseases. The gut microbiome 

 is a key player in the diet-health axis, but while its bacterial 

 fraction is widely studied, the role of micro-eukaryotes, 

 including Blastocystis, is underexplored. We performed a 

 global-scale analysis on 56,989 metagenomes and showed that 

 human Blastocystis exhibits distinct prevalence patterns linked 

 to geography, lifestyle, and dietary habits. Blastocystis 

 presence defined a specific bacterial signature and was 

 positively associated with more favorable cardiometabolic 

 profiles and negatively with obesity (p < 1e-16) and disorders 

 linked to altered gut ecology (p < 1e-8). In a diet intervention 

 study involving 1,124 individuals, improvements in dietary 

 quality were linked to weight loss and increases in Blastocystis prevalence (p = 0.003) and abundance (p < 1e-7). Our findings 

 suggest a potentially beneficial role for Blastocystis, which 

 may help explain personalized host responses to diet and 

 downstream disease etiopathogenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Piperni2024-ph,

title = {Intestinal Blastocystis is linked to healthier diets and more  favorable cardiometabolic outcomes in 56,989 individuals from 32  countries},

author = {Elisa Piperni and Long H Nguyen and Paolo Manghi and Hanseul Kim and Edoardo Pasolli and Sergio Andreu-Sánchez and Alberto Arr`e and Kate M Bermingham and Aitor Blanco-M'iguez and Serena Manara and Mireia Valles-Colomer and Elco Bakker and Fabio Busonero and Richard Davies and Edoardo Fiorillo and Francesca Giordano and George Hadjigeorgiou and Emily R Leeming and Monia Lobina and Marco Masala and Andrea Maschio and Lauren J McIver and Mauro Pala and Maristella Pitzalis and Jonathan Wolf and Jingyuan Fu and Alexandra Zhernakova and Simone M Cacci`o and Francesco Cucca and Sarah E Berry and Danilo Ercolini and Andrew T Chan and Curtis Huttenhower and Tim D Spector and Nicola Segata and Francesco Asnicar},

doi = {10.1016/j.cell.2024.06.018},

year  = {2024},

date = {2024-08-01},

urldate = {2024-08-01},

journal = {Cell},

volume = {187},

number = {17},

pages = {4554--4570.e18},

publisher = {Elsevier BV},

abstract = {Diet impacts human health, influencing body adiposity and the 

 risk of developing cardiometabolic diseases. The gut microbiome 

 is a key player in the diet-health axis, but while its bacterial 

 fraction is widely studied, the role of micro-eukaryotes, 

 including Blastocystis, is underexplored. We performed a 

 global-scale analysis on 56,989 metagenomes and showed that 

 human Blastocystis exhibits distinct prevalence patterns linked 

 to geography, lifestyle, and dietary habits. Blastocystis 

 presence defined a specific bacterial signature and was 

 positively associated with more favorable cardiometabolic 

 profiles and negatively with obesity (p < 1e-16) and disorders 

 linked to altered gut ecology (p < 1e-8). In a diet intervention 

 study involving 1,124 individuals, improvements in dietary 

 quality were linked to weight loss and increases in Blastocystis prevalence (p = 0.003) and abundance (p < 1e-7). Our findings 

 suggest a potentially beneficial role for Blastocystis, which 

 may help explain personalized host responses to diet and 

 downstream disease etiopathogenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2024-hd,

title = {Implications of disease-modifying therapies for multiple  sclerosis on immune cells and response to COVID-19 vaccination},

author = {Valeria Örr`u and Valentina Serra and Michele Marongiu and Sandra Lai and Valeria Lodde and Magdalena Zoledziewska and Maristella Steri and Annalisa Loizedda and Monia Lobina and Maria Grazia Piras and Francesca Virdis and Giuseppe Delogu and Maria Giuseppina Marini and Maura Mingoia and Matteo Floris and Marco Masala and M Paola Castelli and Rafaela Mostallino and Jessica Frau and Lorena Lorefice and Gabriele Farina and Marzia Fronza and Daniele Carmagnini and Elisa Carta and Silvy Pilotto and Paola Chessa and Marcella Devoto and Paolo Castiglia and Paolo Solla and Roberto Ignazio Zarbo and Maria Laura Idda and Maristella Pitzalis and Eleonora Cocco and Edoardo Fiorillo and Francesco" Cucca},

doi = {10.3389/fimmu.2024.1416464},

year  = {2024},

date = {2024-07-01},

urldate = {2024-07-01},

journal = {Front. Immunol.},

volume = {15},

pages = {1416464},

publisher = {Frontiers Media SA},

abstract = {Introduction: Disease-modifying therapies (DMTs) have been shown 

 to improve disease outcomes in multiple sclerosis (MS) patients. 

 They may also impair the immune response to vaccines, including 

 the SARS-CoV-2 vaccine. However, available data on both the 

 intrinsic immune effects of DMTs and their influence on cellular 

 response to the SARS-CoV-2 vaccine are still incomplete. 

 Methods: Here, we evaluated the immune cell effects of 3 DMTs on 

 the response to mRNA SARS-CoV-2 vaccination by comparing MS 

 patients treated with one specific therapy (fingolimod, dimethyl 

 fumarate, or natalizumab) with both healthy controls and 

 untreated patients. We profiled 23 B-cell traits, 57 T-cell 

 traits, and 10 cytokines, both at basal level and after 

 stimulation with a pool of SARS-CoV-2 spike peptides, in 79 MS 

 patients, treated with DMTs or untreated, and 32 healthy 

 controls. Measurements were made before vaccination and at three 

 time points after immunization. Results and Discussion: MS 

 patients treated with fingolimod showed the strongest immune 

 cell dysregulation characterized by a reduction in all measured 

 lymphocyte cell classes; the patients also had increased immune 

 cell activation at baseline, accompanied by reduced specific 

 immune cell response to the SARS-CoV-2 vaccine. Also, anti-spike 

 specific B cells progressively increased over the three time 

 points after vaccination, even when antibodies measured from the 

 same samples instead showed a decline. Our findings demonstrate 

 that repeated booster vaccinations in MS patients are crucial to 

 overcoming the immune cell impairment caused by DMTs and 

 achieving an immune response to the SARS-CoV-2 vaccine 

 comparable to that of healthy controls.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serra2024-gb,

title = {A large-scale screening identified in USH2A gene the P3272L  founder pathogenic variant explaining familial Usher syndrome in  Sardinia, Italy},

author = {Rita Serra and Vincenzo Rallo and Maristella Steri and Stefania Olla and Maria Grazia Piras and Michele Marongiu and Myriam Gorospe and David Schlessinger and Antonio Pinna and Edoardo Fiorillo and Francesco Cucca and Andrea Angius},

year  = {2024},

date = {2024-07-01},

urldate = {2024-07-01},

journal = {BMC Ophthalmol.},

volume = {24},

number = {1},

pages = {306},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: Usher syndrome (USH) encompasses a group of 

 disorders characterized by congenital sensorineural hearing loss 

 (SNHL) and retinitis pigmentosa (RP). We described the clinical 

 findings, natural history, and molecular analyses of USH 

 patients identified during a large-scale screening to identify 

 quantitative traits related to ocular disorders in the SardiNIA 

 project cohort. METHODS: We identified 3 USH-affected families 

 out of a cohort of 6,148 healthy subjects. 9 subjects presented 

 a pathological phenotype, with SNHL and RP. All patients and 

 their family members underwent a complete ophthalmic examination 

 including best-corrected visual acuity, slit-lamp biomicroscopy, 

 fundoscopy, fundus autofluorescence, spectral-domain optical 

 coherence tomography, and electrophysiological testing. 

 Audiological evaluation was performed with a clinical 

 audiometer. Genotyping was performed using several arrays 

 integrated with whole genome sequence data providing 

 approximately 22 million markers equally distributed for each 

 subject analyzed. Molecular diagnostics focused on analysis of 

 the following candidate genes: MYO7A, USH1C, CDH23, PCDH15, 

 USH1G, CIB2, USH2A, GPR98, DFNB31, CLRN1, and PDZD7. RESULTS: A 

 single missense causal variant in USH2A gene was identified in 

 homozygous status in all patients and in heterozygous status in 

 unaffected parents. The presence of multiple homozygous patients 

 with the same phenotypic severity of the syndromic form suggests 

 that the Sardinian USH phenotype is the result of a founder 

 effect on a specific pathogenic variant related haplotype. The 

 frequency of heterozygotes in general Sardinian population is 

 1.89. Additionally, to provide new insights into the structure 

 of usherin and the pathological mechanisms caused by small 

 pathogenic in-frame variants, like p.Pro3272Leu, molecular 

 dynamics simulations of native and mutant protein-protein and 

 protein-ligand complexes were performed that predicted a 

 destabilization of the protein with a decrease in the free 

 energy change. CONCLUSIONS: Our results suggest that our 

 approach is effective for the genetic diagnosis of USH. Based on 

 the heterozygous frequency, targeted screening of this variant 

 in the general population and in families at risk or with 

 familial USH can be suggested. This can lead to more accurate 

 molecular diagnosis, better genetic counseling, and improved 

 molecular epidemiology data that are critical for future 

 intervention plans. TRIAL REGISTRATION: We did not perform any 

 health-related interventions for the participants.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38672460,

title = {The Antioxidant Drug Edaravone Binds to the Aryl Hydrocarbon Receptor (AHR) and Promotes the Downstream Signaling Pathway Activation},

author = {C. Veroni and S. Olla and M. S. Brignone and C. Siguri and A. Formato and M. Marra and R. Manzoli and M. C. Macario and E. Ambrosini and E. Moro and C. Agresti},

year  = {2024},

date = {2024-04-04},

journal = {Biomolecules},

volume = {14},

number = {4},

abstract = {A considerable effort has been spent in the past decades to develop targeted therapies for the treatment of demyelinating diseases, such as multiple sclerosis (MS). Among drugs with free radical scavenging activity and oligodendrocyte protecting effects, Edaravone (Radicava) has recently received increasing attention because of being able to enhance remyelination in experimental in vitro and in vivo disease models. While its beneficial effects are greatly supported by experimental evidence, there is a current paucity of information regarding its mechanism of action and main molecular targets. By using high-throughput RNA-seq and biochemical experiments in murine oligodendrocyte progenitors and SH-SY5Y neuroblastoma cells combined with molecular docking and molecular dynamics simulation, we here provide evidence that Edaravone triggers the activation of aryl hydrocarbon receptor (AHR) signaling by eliciting AHR nuclear translocation and the transcriptional-mediated induction of key cytoprotective gene expression. We also show that an Edaravone-dependent AHR signaling transduction occurs in the zebrafish experimental model, associated with a downstream upregulation of the NRF2 signaling pathway. We finally demonstrate that its rapid cytoprotective and antioxidant actions boost increased expression of the promyelinating Olig2 protein as well as of an Olig2:GFP transgene in vivo. We therefore shed light on a still undescribed potential mechanism of action for this drug, providing further support to its therapeutic potential in the context of debilitating demyelinating conditions.},

note = {[PubMed Central:hrefhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948512PMC2948512] [DOI:hrefhttps://dx.doi.org/10.1371/journal.pone.001312810.1371/journal.pone.0013128] [PubMed:hrefhttps://www.ncbi.nlm.nih.gov/pubmed/2095704620957046]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pintori2024-na,

title = {Immune and glial cell alterations in the rat brain after  repeated exposure to the synthetic cannabinoid JWH-018},

author = {Nicholas Pintori and Rafaela Mostallino and Enrica Spano and Valeria Orr`u and Maria Grazia Piras and Maria Paola Castelli and Maria Antonietta De Luca},

doi = {10.1016/j.jneuroim.2024.578325},

year  = {2024},

date = {2024-04-01},

urldate = {2024-04-01},

journal = {J. Neuroimmunol.},

volume = {389},

number = {578325},

pages = {578325},

publisher = {Elsevier BV},

abstract = {The use of synthetic cannabinoid receptor agonists (SCRAs) poses 

 major psychiatric risks. We previously showed that repeated 

 exposure to the prototypical SCRA JWH-018 induces alterations in 

 dopamine (DA) transmission, abnormalities in the emotional 

 state, and glial cell activation in the mesocorticolimbic DA 

 circuits of rats. Despite growing evidence suggesting the 

 relationship between substance use disorders (SUD) and 

 neuroinflammation, little is known about the impact of SCRAs on 

 the neuroimmune system. Here, we investigated whether repeated 

 JWH-018 exposure altered neuroimmune signaling, which could be 

 linked with previously reported central effects. Adult male 

 Sprague-Dawley (SD) rats were exposed to JWH-018 (0.25 mg/kg, 

 i.p.) for fourteen consecutive days, and the expression of 

 cytokines, chemokines, and growth factors was measured seven 

 days after treatment discontinuation in the striatum, cortex, 

 and hippocampus. Moreover, microglial (ionized calcium-binding 

 adaptor molecule 1, IBA-1) and astrocyte (glial fibrillary 

 acidic protein, GFAP) activation markers were evaluated in the 

 caudate-putamen (CPu). Repeated JWH-018 exposure induces a 

 perturbation of neuroimmune signaling specifically in the 

 striatum, as shown by increased levels of cytokines 

 [interleukins (IL) -2, -4, -12p70, -13, interferon (IFN) 

 $gamma$], chemokines [macrophage inflammatory protein (MIP) 

 -1$alpha$, -3$alpha$], and growth factors [macrophage 

 colony-stimulating factor (M-CSF), vascular endothelial growth 

 factor (VEGF)], together with increased IBA-1 and GFAP 

 expression in the CPu. JWH-018 exposure induces persistant brain 

 region-specific immune alterations up to seven days after drug 

 discontinuation, which may contribute to the behavioral and 

 neurochemical dysregulations in striatal areas that play a role 

 in the reward-related processes that are frequently impaired in 

 SUD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Forabosco2024-jt,

title = {Transcriptome organization of white blood cells through gene  co-expression network analysis in a large RNA-seq dataset},

author = {Paola Forabosco and Mauro Pala and Francesca Crobu and Maria Antonietta Diana and Mara Marongiu and Roberto Cusano and Andrea Angius and Maristella Steri and Valeria Orr`u and David Schlessinger and Edoardo Fiorillo and Marcella Devoto and Francesco Cucca},

doi = {10.3389/fimmu.2024.1350111},

year  = {2024},

date = {2024-04-01},

urldate = {2024-04-01},

journal = {Front. Immunol.},

volume = {15},

pages = {1350111},

abstract = {Gene co-expression network analysis enables identification of 

 biologically meaningful clusters of co-regulated genes (modules) 

 in an unsupervised manner. We present here the largest study 

 conducted thus far of co-expression networks in white blood cells 

 (WBC) based on RNA-seq data from 624 individuals. We identify 41 

 modules, 13 of them related to specific immune-related functions 

 and cell types (e.g. neutrophils, B and T cells, NK cells, and 

 plasmacytoid dendritic cells); we highlight biologically relevant 

 lncRNAs for each annotated module of co-expressed genes. We 

 further characterize with unprecedented resolution the modules in 

 T cell sub-types, through the availability of 95 immune 

 phenotypes obtained by flow cytometry in the same individuals. 

 This study provides novel insights into the transcriptional 

 architecture of human leukocytes, showing how network analysis 

 can advance our understanding of coding and non-coding gene 

 interactions in immune system cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sterzi2024-xo,

title = {Genetic barriers more than environmental associations explain 

 Serratia marcescens population structure},

author = {Lodovico Sterzi and Riccardo Nodari and Federico Di Marco and Maria Laura Ferrando and Francesca Saluzzo and Andrea Spitaleri and Hamed Allahverdi and Stella Papaleo and Simona Panelli and Sara Giordana Rimoldi and Gherard Batisti Biffignandi and Marta Corbella and Annalisa Cavallero and Paola Prati and Claudio Farina and Daniela Maria Cirillo and Gianvincenzo Zuccotti and Claudio Bandi and Francesco Comandatore},

year  = {2024},

date = {2024-04-01},

journal = {Commun. Biol.},

volume = {7},

number = {1},

pages = {468},

abstract = {Bacterial species often comprise well-separated lineages, likely 

 emerged and maintained by genetic isolation and/or ecological 

 divergence. How these two evolutionary actors interact in the 

 shaping of bacterial population structure is currently not fully 

 understood. In this study, we investigate the genetic and 

 ecological drivers underlying the evolution of Serratia 

 marcescens, an opportunistic pathogen with high genomic 

 flexibility and able to colonise diverse environments. 

 Comparative genomic analyses reveal a population structure 

 composed of five deeply-demarcated genetic clusters with open 

 pan-genome but limited inter-cluster gene flow, partially 

 explained by Restriction-Modification (R-M) systems 

 incompatibility. Furthermore, a large-scale research on 

 hundred-thousands metagenomic datasets reveals only a partial 

 habitat separation of the clusters. Globally, two clusters only 

 show a separate gene composition coherent with ecological 

 adaptations. These results suggest that genetic isolation has 

 preceded ecological adaptations in the shaping of the species 

 diversity, an evolutionary scenario coherent with the 

 Evolutionary Extended Synthesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{,

title = {Iodinated 4,4’-Bipyridines with Antiproliferative Activity Against Melanoma Cell Lines},

author = {Peluso Paola and Mamane Victor and Spissu Ylenia and Casu Giuseppina and Dessì Alessandro and Dallocchio Roberto and Sechi Barbara and Palmieri Giuseppe and Rozzo Carla. },

url = {https://irgb.cnr.it/chemmedchem-2024-peluso-et-al-2024-2/},

doi = {doi.org/10.1002/cmdc.202300662},

issn = {1860-7187},

year  = {2024},

date = {2024-03-15},

urldate = {2024-03-15},

journal = {Chemical Medicinal Chemistry},

number = {e202300662},

pages = {1-12},

abstract = {In the last decade, biological processes involving halogen bond (HaB) as a leading interaction attracted great interest. Iodinated 4,4’-bipyridines showed interesting properties as HaB donors in solution and in the solid state. This study represents a proof-of-principle exploration aiming to investigate the effectiveness of new iodinated compounds against melanoma cells. The authors investigated on the inhibition activity exerted by seven halogenated 4,4’-bipyridines on malignant melanoma cell proliferation. The 3,3’,5,5’-tetrachloro-2-iodo-4,4’-bipyridine showed significant antiproliferation activity against the A375 cell line, and lower toxicity on BJ fibroblasts. The results suggested that the antiproliferative activity, at molecular level, may be correlated with the electrophilic properties of iodine. Through in silico studies, the stereoelectronic features of possible sites determining the bioactivity were explored. The obtained results confirmed the high potential of iodinated compounds in designing novel anti-melanoma therapeutics strategies considering the utilization of iodinated 4,4’-bipyridines as templates to design new promising HaB-enabled inhibitors of MM cell proliferation, paving the way for a new perspective in this field.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38280995,

title = {Combination of mutations in genes controlling DNA repair and high mutational load plays a prognostic role in pancreatic ductal adenocarcinoma (PDAC): a retrospective real-life study in Sardinian population},

author = {Maria Cristina Sini and Maria Grazia Doro and Laura Frogheri and Angelo Zinellu and Panagiotis Paliogiannis and Alberto Porcu and Fabrizio Scognamillo and Daniele Delogu and Davide Adriano Santeufemia and Ivana Persico and Grazia Palomba and Giovanni Battista Maestrale and Antonio Cossu and Giuseppe Palmieri},

doi = {10.1186/s12967-024-04923-3},

issn = {1479-5876},

year  = {2024},

date = {2024-01-27},

urldate = {2024-01-27},

journal = {J Transl Med},

volume = {22},

number = {1},

pages = {108},

abstract = {BACKGROUND: Patients with pancreatic ductal adenocarcinoma (PDCA) carrying impaired mismatch repair mechanisms seem to have an outcome advantage under treatment with conventional chemotherapy, whereas the role for the tumor mutation burden on prognosis is controversial. In this study, we evaluated the prognostic role of the mutated genes involved in genome damage repair in a real-life series of PDAC patients in a hospital-based manner from the main Institution deputed to surgically treat such a disease in North Sardinia.



METHODS: A cohort of fifty-five consecutive PDAC patients with potentially resectable/border line resectable PDAC (stage IIB-III) or oligometastatic disease (stage IV) and tumor tissue availability underwent next-generation sequencing (NGS)-based analysis using a panel containing driver oncogenes and tumor suppressor genes as well as genes controlling DNA repair mechanisms.



RESULTS: Genes involved in the both genome damage repair (DR) and DNA mismatch repair (MMR) were found mutated in 17 (31%) and 15 (27%) cases, respectively. One fourth of PDAC cases (14/55; 25.5%) carried tumors presenting a combination of mutations in repair genes (DR and MMR) and the highest mutation load rates (MLR-H). After correction for confounders (surgery, adjuvant therapy, stage T, and metastasis), multivariate Cox regression analysis indicated that mutations in DR genes (HR = 3.0126, 95% CI 1.0707 to 8.4764, p = 0.0367) and the MLR (HR = 1.0018, 95%CI 1.0005 to 1.0032, p = 0.009) were significantly related to worse survival.



CONCLUSIONS: The combination of mutated repair genes and MLR-H, which is associated with a worse survival in our series of PDAC patients treated with conventional chemotherapy protocols, might become a predictive biomarker of response to immunotherapy in addition to its prognostic role in predicting survival.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial},

author = {Paolo A. Ascierto and Milena Casula and Jenny Bulgarelli and Marina Pisano and Claudia Piccinini and Luisa Piccin and Antonio Cossu and Mario Mandalà and Pier Francesco Ferrucci and Massimo Guidoboni and Piotr Rutkowski and Virginia Ferraresi and Ana Arance and Michele Guida and Evaristo Maiello and Helen Gogas and Erika Richtig and Maria Teresa Fierro and Celeste Lebbe and Hildur Helgadottir and Paola Queirolo and Francesco Spagnolo and Marco Tucci and Michele Del Vecchio and Maria Gonzales Cao and Alessandro Marco Minisini and Sabino De Placido and Miguel F. Sanmamed and Domenico Mallardo and Miriam Paone and Maria Grazia Vitale and Ignacio Melero and Antonio M. Grimaldi and Diana Giannarelli and Reinhard Dummer and Vanna Chiarion Sileni and Giuseppe Palmieri.},

url = {https://irgb.cnr.it/wp-content/uploads/2024/05/Ascierto-et-al-2024-Nat-Comm.pdf},

doi = {https://doi.org/10.1038/s41467-023-44475-6},

year  = {2024},

date = {2024-01-15},

urldate = {2024-01-15},

journal = {Nature Communications},

volume = {15},

number = {146},

abstract = {No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, non comparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients

with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37895071,

title = {Inhibitory Effect of Quercetin on Oxidative Endogen Enzymes: A Focus on Putative Binding Modes},

author = {S. Olla and C. Siguri and A. Fais and B. Era and M. C. Fantini and A. "Di Petrillo},

year  = {2023},

date = {2023-10-20},

urldate = {2023-10-20},

journal = {Int J Mol Sci},

volume = {24},

number = {20},

abstract = {Oxidative stress is defined as an imbalance between the production of free radicals and reactive oxygen species (ROS) and the ability of the body to neutralize them by anti-oxidant defense systems. Cells can produce ROS during physiological processes, but excessive ROS can lead to non-specific and irreversible damage to biological molecules, such as DNA, lipids, and proteins. Mitochondria mainly produce endogenous ROS during both physiological and pathological conditions. Enzymes like nicotinamide adenine dinucleotide phosphate oxidase (NOX), xanthine oxidase (XO), lipoxygenase (LOX), myeloperoxidase (MPO), and monoamine oxidase (MAO) contribute to this process. The body has enzymatic and non-enzymatic defense systems to neutralize ROS. The intake of bioactive phenols, like quercetin (Que), can protect against pro-oxidative damage by quenching ROS through a non-enzymatic system. In this study, we evaluate the ability of Que to target endogenous oxidant enzymes involved in ROS production and explore the mechanisms of action underlying its anti-oxidant properties. Que can act as a free radical scavenger by donating electrons through the negative charges in its phenolic and ketone groups. Additionally, it can effectively inhibit the activity of several endogenous oxidative enzymes by binding them with high affinity and specificity. Que had the best molecular docking results with XO, followed by MAO-A, 5-LOX, NOX, and MPO. Que's binding to these enzymes was confirmed by subsequent molecular dynamics, revealing different stability phases depending on the enzyme bound. The 500 ns simulation showed a net evolution of binding for NOX and MPO. These findings suggest that Que has potential as a natural therapy for diseases related to oxidative stress.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37836771,

title = {Synthesis and Characterization of Edaravone Analogues as Remyelinating Agents and Putative Mechanistic Probes},

author = {E. Colombo and S. Olla and C. Minnelli and A. Formato and C. Veroni and S. Corbisiero and M. Pericolo and C. Siguri and G. Mobbili and C. Agresti and P. Seneci},

year  = {2023},

date = {2023-10-04},

volume = {28},

number = {19},

abstract = {as a putative EDA 1 prodrug suitable for in vivo testing.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gussak2023-rj,

title = {Precision genome engineering in streptococcus suis based on a 

 broad-host-range vector and CRISPR-Cas9 technology},

author = {Alex Gussak and Maria Laura Ferrando and Mels Schrama and Peter Baarlen and Jerry Mark Wells},

year  = {2023},

date = {2023-09-01},

journal = {ÄCS Synth. Biol."},

volume = {12},

number = {9},

pages = {2546--2560},

abstract = {Streptococcussuis is an important zoonotic pathogen that causes 

 severe invasive disease in pigs and humans. Current methods for 

 genome engineering of S. suis rely on the insertion of antibiotic 

 resistance markers, which is time-consuming and labor-intensive 

 and does not allow the precise introduction of small genomic 

 mutations. Here we developed a system for CRISPR-based genome 

 editing in S. suis, utilizing linear DNA fragments for homologous 

 recombination (HR) and a plasmid-based negative selection system 

 for bacteria not edited by HR. To enable the use of this system 

 in other bacteria, we engineered a broad-host-range replicon in 

 the CRISPR plasmid. We demonstrated the utility of this system to 

 rapidly introduce multiple gene deletions in successive rounds of 

 genome editing and to make precise nucleotide changes in 

 essential genes. Furthermore, we characterized a mechanism by 

 which S. suis can escape killing by a targeted Cas9-sgRNA complex 

 in the absence of HR. A characteristic of this new mechanism is 

 the presence of very slow-growing colonies in a persister-like 

 state that may allow for DNA repair or the introduction of 

 mutations, alleviating Cas9 pressure. This does not impact the 

 utility of CRISPR-based genome editing because the escape 

 colonies are easily distinguished from genetically edited clones 

 due to their small colony size. Our CRISPR-based editing system 

 is a valuable addition to the genetic toolbox for engineering of 

 S. suis, as it accelerates the process of mutant construction and 

 simplifies the removal of antibiotic markers between successive 

 rounds of genome editing.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Orru2023-vp,

title = {Biomarker dynamics affecting neoadjuvant therapy response and 

 outcome of HER2-positive breast cancer subtype},

author = {Sandra Örr`u and Emanuele Pascariello and Barbara Pes and Vincenzo Rallo and Raffaele Barbara and Marta Muntoni and Francesca Notari and Gianfranco Fancello and Cristina Mocci and Maria Rosaria Muroni and Paolo Cossu-Rocca and Andrea Angius and Maria Rosaria" De Miglio},

year  = {2023},

date = {2023-08-01},

journal = {Sci. Rep.},

volume = {13},

number = {1},

pages = {12869},

publisher = {Springer Science and Business Media LLC},

abstract = {HER2+ breast cancer (BC) is an aggressive subtype genetically 

 and biologically heterogeneous. We evaluate the predictive and 

 prognostic role of HER2 protein/gene expression levels combined 

 with clinico-pathologic features in 154 HER2+ BCs patients who 

 received trastuzumab-based neoadjuvant chemotherapy (NACT). The 

 tumoral pathological complete response (pCR) rate was 40.9%. 

 High tumoral pCR show a scarce mortality rate vs subjects with a 

 lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were 

 HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the 

 remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with 

 a high percentage of infiltrating immune cells and right-sided 

 tumors, that reduce distant metastasis and improve survival, but 

 no incidence difference. HER2 IHC score and laterality emerge as 

 strong predictors of tumoral pCR after NACT from machine 

 learning analysis. HER2 IHC3+ and G3 are poor prognostic factors 

 for HER2+ BC patients, and could be considered in the 

 application of neoadjuvant therapy. Increasing TILs 

 concentrations, lower lymph node ratio and lower residual tumor 

 cellularity are associated with a better outcome. The immune 

 microenvironment and scarce lymph node involvement have crucial 

 role in clinical outcomes. The combination of all predictors 

 might offer new options for NACT effectiveness prediction and 

 stratification of HER2+ BC during clinical decision-making.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {BRAFV600 variant allele frequency predicts outcome in metastatic melanoma patients treated with BRAF and MEK inhibitors.},

author = {Mandalà Mario and Palmieri Giuseppe and Ludovini Vienna and Baglivo Sara and Marasciulo Francesca and Castiglione Francesca and Gili Alessio and Osella Abate Simona and Rubatto Marco and Senetta Rebecca and Avallone Gianluca and Ribero Simone and Romano Luca and Pimpinelli Nicola and de Giorgi Vincenzo and Roila Fausto and Pisano Marina and Casula Milena and Manca Antonella and Sini Maria Cristina},

doi = {10.1111/jdv.19281},

year  = {2023},

date = {2023-06-27},

urldate = {2023-06-27},

journal = {Journal of the European Academy of Dermatology & Venereology},

abstract = {Background: The prognostic impact of variant allele frequency (VAF) on clinical outcome in BRAFV600 mutated metastatic melanoma patients (MMPs) receiving BRAF (BRAFi) and MEK inhibitors (MEKi) is unclear. Materials and methods: A cohort of MMPs receiving first line BRAFi and MEKi was identified by inspecting dedicated databases of three Italian Melanoma Intergroup centres. VAF was determined by next generation sequencing in pre-treatment baseline tissue samples. Correlation between VAF and BRAF copy number variation was analysed in an ancillary study by using a training and a validation cohort of melanoma tissue samples and cell lines.Results: Overall, 107 MMPs were included in the study. The VAF cut-off determined by ROC curve was 41.3%. At multivariate analysis, progression-free survival (PFS) was significantly shorter in patients with M1c/M1d [HR 2.25 (95% CI 1.41-3.6, p < 0.01)], in those with VAF >41.3% [HR 1.62 (95% CI 1.04-2.54, p < 0.05)] and in those with ECOG PS ≥1 [HR 1.82 (95% CI 1.15-2.88, p < 0.05)]. Overall survival (OS) was significantly shorter in patients with M1c/M1d [HR 2.01 (95% CI 1.25-3.25, p < 0.01)]. Furthermore, OS was shorter in patients with VAF >41.3% [HR 1.46 (95% CI 0.93-2.29, p = 0.06)] and in patients with ECOG PS ≥1 [HR 1.52 (95% CI 0.94-2.87, p = 0.14)]. BRAF gene amplification was found in 11% and 7% of samples in the training and validation cohort, respectively. Conclusions: High VAF is an independent poor prognostic factor in MMP receiving BRAFi and MEKi. High VAF and BRAF amplification coexist in 7%-11% of patients. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ahuja2023-spd,

title = {Immune resilience despite inflammatory stress promotes longevity 

 and favorable health outcomes including resistance to infection},

author = {Sunil K Ähuja and Muthu Saravanan Manoharan and Grace C Lee and Lyle R McKinnon and Justin A Meunier and Maristella Steri and Nathan Harper and Edoardo Fiorillo and Alisha M Smith and Marcos I Restrepo and Anne P Branum and Matthew J Bottomley and Valeria Orr`u and Fabio Jimenez and Andrew Carrillo and Lavanya Pandranki and Caitlyn A Winter and Lauryn A Winter and Alvaro A Gaitan and Alvaro G Moreira and Elizabeth A Walter and Guido Silvestri and Christopher L King and Yong-Tang Zheng and Hong-Yi Zheng and Joshua Kimani and T Blake Ball and Francis A Plummer and Keith R Fowke and Paul N Harden and Kathryn J Wood and Martin T Ferris and Jennifer M Lund and Mark T Heise and Nigel Garrett and Kristen R Canady and Salim S Abdool Karim and Susan J Little and Sara Gianella and Davey M Smith and Scott Letendre and Douglas D Richman and Francesco Cucca and Hanh Trinh and Sandra Sanchez-Reilly and Joan M Hecht and Jose A Cadena Zuluaga and Antonio Anzueto and Jacqueline A Pugh and South Texas Veterans Health Care System COVID-19 team and Brian K Agan and Robert Root-Bernstein and Robert A Clark and Jason F Okulicz and Weijing" He},

year  = {2023},

date = {2023-06-01},

journal = {Nat. Commun.},

volume = {14},

number = {1},

pages = {3286},

abstract = {Some people remain healthier throughout life than others but the 

 underlying reasons are poorly understood. Here we hypothesize 

 this advantage is attributable in part to optimal immune 

 resilience (IR), defined as the capacity to preserve and/or 

 rapidly restore immune functions that promote disease resistance 

 (immunocompetence) and control inflammation in infectious 

 diseases as well as other causes of inflammatory stress. We gauge 

 IR levels with two distinct peripheral blood metrics that 

 quantify the balance between (i) CD8+ and CD4+ T-cell levels and 

 (ii) gene expression signatures tracking longevity-associated 

 immunocompetence and mortality-associated inflammation. Profiles 

 of IR metrics in ~48,500 individuals collectively indicate that 

 some persons resist degradation of IR both during aging and when 

 challenged with varied inflammatory stressors. With this 

 resistance, preservation of optimal IR tracked (i) a lower risk 

 of HIV acquisition, AIDS development, symptomatic influenza 

 infection, and recurrent skin cancer; (ii) survival during 

 COVID-19 and sepsis; and (iii) longevity. IR degradation is 

 potentially reversible by decreasing inflammatory stress. 

 Overall, we show that optimal IR is a trait observed across the 

 age spectrum, more common in females, and aligned with a specific 

 immunocompetence-inflammation balance linked to favorable 

 immunity-dependent health outcomes. IR metrics and mechanisms 

 have utility both as biomarkers for measuring immune health and 

 for improving health outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ahuja2023-spc,

title = {Immune resilience despite inflammatory stress promotes longevity 

 and favorable health outcomes including resistance to infection},

author = {Sunil K Ähuja and Muthu Saravanan Manoharan and Grace C Lee and Lyle R McKinnon and Justin A Meunier and Maristella Steri and Nathan Harper and Edoardo Fiorillo and Alisha M Smith and Marcos I Restrepo and Anne P Branum and Matthew J Bottomley and Valeria Orr`u and Fabio Jimenez and Andrew Carrillo and Lavanya Pandranki and Caitlyn A Winter and Lauryn A Winter and Alvaro A Gaitan and Alvaro G Moreira and Elizabeth A Walter and Guido Silvestri and Christopher L King and Yong-Tang Zheng and Hong-Yi Zheng and Joshua Kimani and T Blake Ball and Francis A Plummer and Keith R Fowke and Paul N Harden and Kathryn J Wood and Martin T Ferris and Jennifer M Lund and Mark T Heise and Nigel Garrett and Kristen R Canady and Salim S Abdool Karim and Susan J Little and Sara Gianella and Davey M Smith and Scott Letendre and Douglas D Richman and Francesco Cucca and Hanh Trinh and Sandra Sanchez-Reilly and Joan M Hecht and Jose A Cadena Zuluaga and Antonio Anzueto and Jacqueline A Pugh and South Texas Veterans Health Care System COVID-19 team and Brian K Agan and Robert Root-Bernstein and Robert A Clark and Jason F Okulicz and Weijing" He},

year  = {2023},

date = {2023-06-01},

journal = {Nat. Commun.},

volume = {14},

number = {1},

pages = {3286},

abstract = {Some people remain healthier throughout life than others but the 

 underlying reasons are poorly understood. Here we hypothesize 

 this advantage is attributable in part to optimal immune 

 resilience (IR), defined as the capacity to preserve and/or 

 rapidly restore immune functions that promote disease resistance 

 (immunocompetence) and control inflammation in infectious 

 diseases as well as other causes of inflammatory stress. We gauge 

 IR levels with two distinct peripheral blood metrics that 

 quantify the balance between (i) CD8+ and CD4+ T-cell levels and 

 (ii) gene expression signatures tracking longevity-associated 

 immunocompetence and mortality-associated inflammation. Profiles 

 of IR metrics in ~48,500 individuals collectively indicate that 

 some persons resist degradation of IR both during aging and when 

 challenged with varied inflammatory stressors. With this 

 resistance, preservation of optimal IR tracked (i) a lower risk 

 of HIV acquisition, AIDS development, symptomatic influenza 

 infection, and recurrent skin cancer; (ii) survival during 

 COVID-19 and sepsis; and (iii) longevity. IR degradation is 

 potentially reversible by decreasing inflammatory stress. 

 Overall, we show that optimal IR is a trait observed across the 

 age spectrum, more common in females, and aligned with a specific 

 immunocompetence-inflammation balance linked to favorable 

 immunity-dependent health outcomes. IR metrics and mechanisms 

 have utility both as biomarkers for measuring immune health and 

 for improving health outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ahuja2023-spb,

title = {Immune resilience despite inflammatory stress promotes longevity 

 and favorable health outcomes including resistance to infection},

author = {Sunil K Ähuja and Muthu Saravanan Manoharan and Grace C Lee and Lyle R McKinnon and Justin A Meunier and Maristella Steri and Nathan Harper and Edoardo Fiorillo and Alisha M Smith and Marcos I Restrepo and Anne P Branum and Matthew J Bottomley and Valeria Orr`u and Fabio Jimenez and Andrew Carrillo and Lavanya Pandranki and Caitlyn A Winter and Lauryn A Winter and Alvaro A Gaitan and Alvaro G Moreira and Elizabeth A Walter and Guido Silvestri and Christopher L King and Yong-Tang Zheng and Hong-Yi Zheng and Joshua Kimani and T Blake Ball and Francis A Plummer and Keith R Fowke and Paul N Harden and Kathryn J Wood and Martin T Ferris and Jennifer M Lund and Mark T Heise and Nigel Garrett and Kristen R Canady and Salim S Abdool Karim and Susan J Little and Sara Gianella and Davey M Smith and Scott Letendre and Douglas D Richman and Francesco Cucca and Hanh Trinh and Sandra Sanchez-Reilly and Joan M Hecht and Jose A Cadena Zuluaga and Antonio Anzueto and Jacqueline A Pugh and South Texas Veterans Health Care System COVID-19 team and Brian K Agan and Robert Root-Bernstein and Robert A Clark and Jason F Okulicz and Weijing" He},

year  = {2023},

date = {2023-06-01},

journal = {Nat. Commun.},

volume = {14},

number = {1},

pages = {3286},

abstract = {Some people remain healthier throughout life than others but the 

 underlying reasons are poorly understood. Here we hypothesize 

 this advantage is attributable in part to optimal immune 

 resilience (IR), defined as the capacity to preserve and/or 

 rapidly restore immune functions that promote disease resistance 

 (immunocompetence) and control inflammation in infectious 

 diseases as well as other causes of inflammatory stress. We gauge 

 IR levels with two distinct peripheral blood metrics that 

 quantify the balance between (i) CD8+ and CD4+ T-cell levels and 

 (ii) gene expression signatures tracking longevity-associated 

 immunocompetence and mortality-associated inflammation. Profiles 

 of IR metrics in ~48,500 individuals collectively indicate that 

 some persons resist degradation of IR both during aging and when 

 challenged with varied inflammatory stressors. With this 

 resistance, preservation of optimal IR tracked (i) a lower risk 

 of HIV acquisition, AIDS development, symptomatic influenza 

 infection, and recurrent skin cancer; (ii) survival during 

 COVID-19 and sepsis; and (iii) longevity. IR degradation is 

 potentially reversible by decreasing inflammatory stress. 

 Overall, we show that optimal IR is a trait observed across the 

 age spectrum, more common in females, and aligned with a specific 

 immunocompetence-inflammation balance linked to favorable 

 immunity-dependent health outcomes. IR metrics and mechanisms 

 have utility both as biomarkers for measuring immune health and 

 for improving health outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ahuja2023-sp,

title = {Immune resilience despite inflammatory stress promotes longevity  and favorable health outcomes including resistance to infection},

author = {Sunil K Ähuja and Muthu Saravanan Manoharan and Grace C Lee and Lyle R McKinnon and Justin A Meunier and Maristella Steri and Nathan Harper and Edoardo Fiorillo and Alisha M Smith and Marcos I Restrepo and Anne P Branum and Matthew J Bottomley and Valeria Orr`u and Fabio Jimenez and Andrew Carrillo and Lavanya Pandranki and Caitlyn A Winter and Lauryn A Winter and Alvaro A Gaitan and Alvaro G Moreira and Elizabeth A Walter and Guido Silvestri and Christopher L King and Yong-Tang Zheng and Hong-Yi Zheng and Joshua Kimani and T Blake Ball and Francis A Plummer and Keith R Fowke and Paul N Harden and Kathryn J Wood and Martin T Ferris and Jennifer M Lund and Mark T Heise and Nigel Garrett and Kristen R Canady and Salim S Abdool Karim and Susan J Little and Sara Gianella and Davey M Smith and Scott Letendre and Douglas D Richman and Francesco Cucca and Hanh Trinh and Sandra Sanchez-Reilly and Joan M Hecht and Jose A Cadena Zuluaga and Antonio Anzueto and Jacqueline A Pugh and South Texas Veterans Health Care System COVID-19 team and Brian K Agan and Robert Root-Bernstein and Robert A Clark and Jason F Okulicz and Weijing" He},

doi = {10.1038/s41467-023-38238-6},

year  = {2023},

date = {2023-06-01},

urldate = {2023-06-01},

journal = {Nat. Commun.},

volume = {14},

number = {1},

pages = {3286},

abstract = {Some people remain healthier throughout life than others but the 

 underlying reasons are poorly understood. Here we hypothesize 

 this advantage is attributable in part to optimal immune 

 resilience (IR), defined as the capacity to preserve and/or 

 rapidly restore immune functions that promote disease resistance 

 (immunocompetence) and control inflammation in infectious 

 diseases as well as other causes of inflammatory stress. We gauge 

 IR levels with two distinct peripheral blood metrics that 

 quantify the balance between (i) CD8+ and CD4+ T-cell levels and 

 (ii) gene expression signatures tracking longevity-associated 

 immunocompetence and mortality-associated inflammation. Profiles 

 of IR metrics in ~48,500 individuals collectively indicate that 

 some persons resist degradation of IR both during aging and when 

 challenged with varied inflammatory stressors. With this 

 resistance, preservation of optimal IR tracked (i) a lower risk 

 of HIV acquisition, AIDS development, symptomatic influenza 

 infection, and recurrent skin cancer; (ii) survival during 

 COVID-19 and sepsis; and (iii) longevity. IR degradation is 

 potentially reversible by decreasing inflammatory stress. 

 Overall, we show that optimal IR is a trait observed across the 

 age spectrum, more common in females, and aligned with a specific 

 immunocompetence-inflammation balance linked to favorable 

 immunity-dependent health outcomes. IR metrics and mechanisms 

 have utility both as biomarkers for measuring immune health and 

 for improving health outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ahuja2023-yn,

title = {Immune resilience despite inflammatory stress promotes longevity 

 and favorable health outcomes including resistance to infection},

author = {Sunil K Ähuja and Muthu Saravanan Manoharan and Grace C Lee and Lyle R McKinnon and Justin A Meunier and Maristella Steri and Nathan Harper and Edoardo Fiorillo and Alisha M Smith and Marcos I Restrepo and Anne P Branum and Matthew J Bottomley and Valeria Orr`u and Fabio Jimenez and Andrew Carrillo and Lavanya Pandranki and Caitlyn A Winter and Lauryn A Winter and Alvaro A Gaitan and Alvaro G Moreira and Elizabeth A Walter and Guido Silvestri and Christopher L King and Yong-Tang Zheng and Hong-Yi Zheng and Joshua Kimani and T Blake Ball and Francis A Plummer and Keith R Fowke and Paul N Harden and Kathryn J Wood and Martin T Ferris and Jennifer M Lund and Mark T Heise and Nigel Garrett and Kristen R Canady and Salim S Abdool Karim and Susan J Little and Sara Gianella and Davey M Smith and Scott Letendre and Douglas D Richman and Francesco Cucca and Hanh Trinh and Sandra Sanchez-Reilly and Joan M Hecht and Jose A Cadena Zuluaga and Antonio Anzueto and Jacqueline A Pugh and South Texas Veterans Health Care System COVID-19 team and Brian K Agan and Robert Root-Bernstein and Robert A Clark and Jason F Okulicz and Weijing" He},

year  = {2023},

date = {2023-06-01},

journal = {Nat. Commun.},

volume = {14},

number = {1},

pages = {3286},

abstract = {Some people remain healthier throughout life than others but the 

 underlying reasons are poorly understood. Here we hypothesize 

 this advantage is attributable in part to optimal immune 

 resilience (IR), defined as the capacity to preserve and/or 

 rapidly restore immune functions that promote disease resistance 

 (immunocompetence) and control inflammation in infectious 

 diseases as well as other causes of inflammatory stress. We gauge 

 IR levels with two distinct peripheral blood metrics that 

 quantify the balance between (i) CD8+ and CD4+ T-cell levels and 

 (ii) gene expression signatures tracking longevity-associated 

 immunocompetence and mortality-associated inflammation. Profiles 

 of IR metrics in ~48,500 individuals collectively indicate that 

 some persons resist degradation of IR both during aging and when 

 challenged with varied inflammatory stressors. With this 

 resistance, preservation of optimal IR tracked (i) a lower risk 

 of HIV acquisition, AIDS development, symptomatic influenza 

 infection, and recurrent skin cancer; (ii) survival during 

 COVID-19 and sepsis; and (iii) longevity. IR degradation is 

 potentially reversible by decreasing inflammatory stress. 

 Overall, we show that optimal IR is a trait observed across the 

 age spectrum, more common in females, and aligned with a specific 

 immunocompetence-inflammation balance linked to favorable 

 immunity-dependent health outcomes. IR metrics and mechanisms 

 have utility both as biomarkers for measuring immune health and 

 for improving health outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37232846,

title = {PD-L1 Expression in Cutaneous Angiosarcomas: A Systematic Review with Meta-Analysis},

author = {Renato Lobrano and Panagiotis Paliogiannis and Angelo Zinellu and Giuseppe Palmieri and Ivana Persico and Arduino A Mangoni and Antonio Cossu},

doi = {10.3390/curroncol30050388},

issn = {1718-7729},

year  = {2023},

date = {2023-05-17},

urldate = {2023-05-17},

journal = {Curr Oncol},

volume = {30},

number = {5},

pages = {5135--5144},

abstract = {Cutaneous angiosarcoma (CAS) is the most common type of angiosarcoma that predominantly affects older Caucasians. The outcomes of immunotherapy in CAS are currently under investigation in relation to the expression of programmed death ligand 1 (PD-L1) and other biomarkers. We performed a systematic review and metanalysis of data from the current literature reporting on PD-L1 immunohistochemistry expression. A systematic search of publications in the electronic databases PubMed, Web of Science, and Scopus was conducted using the following terms: "PD-L1" and "angiosarcomas". A total of ten studies reporting on 279 cases were identified and included in the meta-analysis. The pooled prevalence of PD-L1 expression in CAS was 54% (95% CI 36-71%), with high heterogeneity (I = 84.81%,  < 0.001). In sub-group analysis, the proportion of PD-L1 expression in CAS was significantly ( = 0.049) lower in Asian studies (ES = 35%, 95% CI 28-42%, I = 0.0%,  = 0.46) than in European studies (ES = 71%, 95% CI 51-89%, I = 48.91%,  = 0.12).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Comparison between Three Different Techniques for the Detection of EGFR Mutations in Liquid Biopsies of Patients with Advanced Stage Lung Adenocarcinoma},

author = {Casula Milena and Pisano Marina and Paliogiannis Panagiotis and Colombino Maria and Sini Maria Cristina and Zinellu Angelo},

year  = {2023},

date = {2023-03-29},

urldate = {2023-03-29},

journal = {International Journal of Molecular Sciences},

volume = {24},

number = {6410},

abstract = {Oncogenic mutations in the EGFR gene are targets of tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma (LC) patients and their search is mandatory to make decisions on treatment strategies. Liquid biopsy of circulating tumour DNA (ctDNA) is increasingly used to detect EGFR mutations including main activating alterations (exon 19 deletions and exon 21 L858R mutation) and T790M mutation which is the most common mechanism of acquired resistance to first- and second-generation TKIs. In this study we prospectively compared three different techniques for EGFR mutation detection in liquid biopsies of such patients. Fifty-four ctDNA samples from 48 consecutive advanced LC patients treated with TKIs were tested for relevant EGFR mutations with Therascreen® EGFR Plasma RGQ-PCR Kit (Qiagen). Samples were subsequently tested with two different technologies with the aim to compare the EGFR detection rates: real-time PCR based Idylla™ ctEGFR mutation assay (Biocartis) and next-generation sequencing (NGS) system with Ion AmpliSeq Cancer Hotspot panel (ThermoFisher). A high concordance rate for main druggable EGFR alterations was observed with the two real-time PCR-based assays ranging from 100% for T790M mutation to 94% for L858R variant and 85% for exon 19 deletions. Conversely lower concordance rates were found between real-time PCR approaches and the NGS method (L858R: 88%; exon19-dels: 74%; T790M: 37.5%). Our results evidenced an equivalent detection ability between PCR-based techniques for circulating EGFR mutations. The NGS assay allowed detection of a wider range of EGFR mutations but showed a poor ability to detect T790M.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serra2023-ve,

title = {Polygenic risk score and biochemical/environmental variables 

 predict a low-risk profile of age-related macular degeneration 

 in Sardinia},

author = {Rita Serra and Vincenzo Rallo and Antonio Pinna and Maristella Steri and Maria Grazia Piras and Michele Marongiu and Florence Coscas and Myriam Gorospe and David Schlessinger and Edoardo Fiorillo and Francesco Cucca and Andrea Angius},

year  = {2023},

date = {2023-03-01},

journal = {Ärbeitsphysiologie"},

volume = {261},

number = {3},

pages = {691--698},

publisher = {Springer Science and Business Media LLC},

abstract = {PURPOSE: To ascertain the prevalence and clinical and genetic 

 features of age-related macular degeneration (AMD) in subjects 

 living in the Lanusei valley, Central Sardinia, Italy, involved 

 in a study on ageing (SardiNIA project). METHODS: A total of 814 

 volunteers aged $geq$ 50 years, randomly selected from the 

 SardiNIA project dataset, were included. A color fundus (CF) 

 photograph of the 30° central retina of each eye was obtained 

 and graded according to the Age-Related Eye Disease Study 

 system. Life-style choices were investigated using standardized 

 questionnaires. The concentrations of several inflammatory 

 biomarkers (i.e., complement component, fibrinogen, and 

 C-reactive protein) were measured. Polygenic risk score (PRS) 

 was calculated and compared with results obtained from a 

 European cohort. RESULTS: A total of 756 subjects had gradable 

 CF photographs for AMD detection. In 91.3%, no signs of AMD 

 were observed. The prevalence rates of early and late AMDs were 

 6.9% and 0.6%, respectively. A total of 85% of subjects were 

 physically active; only 13.5% were current smokers. Low 

 concentrations of complement component, fibrinogen, and 

 C-reactive protein were found. We calculated the polygenic risk 

 scores (PRS) using 40 AMD markers distributed on several 

 candidate genes in Europeans and Sardinians. The mean PRS value 

 was significantly lower in Sardinians than in the Europeans (0.21 vs. 0.248, respectivel},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36425957,

title = {CFDP1 is a neuroblastoma susceptibility gene that regulates transcription factors of the noradrenergic cell identity},

author = {D. Formicola and V. A. Lasorsa and S. Cantalupo and A. Testori and A. Cardinale and M. Avitabile and S. Diskin and A. Iolascon and M. Capasso},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {HGG Adv},

volume = {4},

number = {1},

pages = {100158},

abstract = {acts as oncogene in NB. In addition, we provide evidence that genetic predisposition to NB can be mediated by the alteration of noradrenergic lineage-specific gene expression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serra2022-xa,

title = {Quantifying the detrimental effects of multiple freeze/thaw  cycles on primary human lymphocyte survival and function},

author = {Valentina Serra and Edoardo Fiorillo and Francesco Cucca and Valeria Orr`u},

doi = {10.3390/ijms24010634.},

year  = {2022},

date = {2022-12-01},

urldate = {2022-12-01},

journal = {Int. J. Mol. Sci.},

volume = {24},

number = {1},

pages = {634},

publisher = {MDPI AG},

abstract = {The use of cryopreserved peripheral blood mononuclear cells is 

 common in biological research. It is widely accepted that 

 primary cells are rendered unusable by several freezing cycles, 

 although this practice might be very helpful when the biological 

 material is valuable and its re-collection is impractical. To 

 determine the extent to which primary cells undergoing repeated 

 freezing cycles are comparable to one another and to fresh 

 samples, we evaluated overall lymphocyte viability, their 

 proliferation and cytokine production capabilities, as well as 

 the levels of 27 cell subtypes in ten human peripheral blood 

 mononuclear cells frozen for five years and repeatedly thawed. 

 As expected, we observed a progressive increase in cell death 

 percentages on three rounds of thawing, but the frequency of the 

 main lymphocyte subsets was stable across the three thawings. 

 Nevertheless, we observed a significant reduction of B cell 

 frequency in frozen samples compared to fresh ones. On repeated 

 thawings and subsequent conventional stimulation, lymphocyte 

 proliferation significantly decreased, and IL-10, IL-6, GM-CSF, 

 IFN-gamma, and IL-8 showed a trend to lower values.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis},

author = {Gaia Rocchitta and Carla Rozzo and Marina Pisano and Davide Fabbri and Maria Antonietta Dettori and

Paolo Ruzza and Claudia Honisch and Roberto Dallocchio and Alessandro Dessì and Rossana Migheli and

PierAndrea Serra and Giovanna Delogu},

url = {https://doi.org/10.3390/molecules27227942

https://irgb.cnr.it/wp-content/uploads/2024/05/Rocchitta-et-al-2022-2.pdf},

doi = {https://doi.org/10.3390/molecules27227942},

year  = {2022},

date = {2022-11-16},

urldate = {2022-11-16},

journal = {Molecules},

volume = {27},

number = {7942},

pages = {1-24},

abstract = {Tyrosinase is a well-known copper-containing metalloenzyme typically involved in the synthesis of melanin. Recently, curcumin and several synthetic derivatives have been recognized as tyrosinase inhibitors with interesting anti-melanogenic therapeutic activity. In this study, three curcumin-inspired compounds 1, 6 and 7 were prepared in yields ranging from 60 to 88 % and spectrophotometric, electrochemical, in vitro and in silico analyses were carried out. The viability of PC12 cells, a rat pheochromocytoma derived-cell line, with compounds 1, 6 and 7, showed values around 80% at 5 uM concentration. In cell proliferation assays, compounds 1, 6 and 7 did not show significant toxicity on fibroblasts nor melanoma cells up to 10 uM with viability values over 90%. The inhibition of tyrosinase activity was evaluated both by a UV-Vis spectroscopic method at two different concentrations, 0.2 and 2.0 uM, and by amperometric assay with IC50 for compounds 1, 6 and 7 ranging from 11 to 24 nM. Melanin content assays on human melanoma cells were performed to test the capability of compounds to inhibit melanin biosynthesis. All compounds exerted a decrease in melanin content, with compound 7 being the most effective by showing a melanogenesis inhibition up to four times greater than arbutin at 100 uM. Moreover, the antioxidant activity of the selected inhibitors was evaluated against H2O2 in amperometric experiments, whereby compound 7 was about three times more effective compared to compounds 1 and 6. The tyrosinase X-ray structure of Bacterium megaterium crystal was used to carry out molecular docking studies in the presence of compounds 1, 6 and 7 in comparison with that of kojic acid and arbutin, two conventional tyrosinase inhibitors. Molecular docking of compounds 6 and 7 confirmed the high affinity of these compounds to tyrosinase protein.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36543896,

title = {Analysis of the oral microbiome during hormonal cycle and its alterations in menopausal women: the },

author = {A Tramice and D Paris and A Manca and F A Guevara Agudelo and S Petrosino and L Siracusa and M Carbone and D Melck and F Raymond and F Piscitelli},

doi = {10.1038/s41598-022-26528-w},

issn = {2045-2322},

year  = {2022},

date = {2022-09-21},

journal = {Sci Rep},

volume = {12},

number = {1},

pages = {22086},

abstract = {The maintenance of human health is dependent on a symbiotic relationship between humans and associated bacteria. The diversity and abundance of each habitat's signature microbes vary widely among body areas and among them the oral microbiome plays a key role. Significant changes in the oral cavity, predominantly at salivary and periodontal level, have been associated with changes in estrogen levels. However, whether the oral microbiome is affected by hormonal level alterations is understudied. Hence the main objective pursued by AMICA project was to characterize the oral microbiome (saliva) in healthy women through: profiling studies using "omics" technologies (NMR-based metabolomics, targeted lipidomics by LC-MS, metagenomics by NGS); SinglePlex ELISA assays; glycosidase activity analyses and bioinformatic analysis. For this purpose, thirty-nine medically healthy women aged 26-77 years (19 with menstrual cycle and 20 in menopause) were recruited. Participants completed questionnaires assessing detailed medical and medication history and demographic characteristics. Plasmatic and salivary levels of sexual hormones were assessed (FSH, estradiol, LH and progesteron) at day 3 and 14 for women with menstrual cycle and only once for women in menopause. Salivary microbiome composition was assessed through meta-taxonomic 16S sequencing and overall, the salivary microbiome of most women remained relatively stable throughout the menstrual cycle and in menopause. Targeted lipidomics and untargeted metabolomics profiling were assessed through the use of LC-MS and NMR spectroscopy technologies, respectively and significant changes in terms of metabolites were identified in saliva of post-menopausal women in comparison to cycle. Moreover, glycosyl hydrolase activities were screened and showed that the β-D-hexosaminidase activity was the most present among those analyzed. Although this study has not identified significant alterations in the composition of the oral microbiome, multiomics analysis have revealed a strong correlation between 2-AG and α-mannosidase. In conclusion, the use of a multidisciplinary approach to investigate the oral microbiome of healthy women provided some indication about microbiome-derived predictive biomarkers that could be used in the future for developing new strategies to help to re-establish the correct hormonal balance in post-menopausal women.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35601448,

title = {Aquivion perfluorosulfonic superacid as an effective catalyst for selective epoxidation of vegetable oils},

author = {Riccardo Polese and Elisa Pintus and Luca Nuvoli and Monica Tiana and Salvatore Pintus and Giuseppe Satta and Andrea Beccu and Silvia Gaspa and Massimo Carraro and Lidia De Luca and Ugo Azzena and Luisa Pisano},

doi = {10.1098/rsos.211554},

issn = {2054-5703},

year  = {2022},

date = {2022-09-06},

journal = {R Soc Open Sci},

volume = {9},

number = {4},

pages = {211554},

abstract = {The acid-promoted epoxidation of vegetable oils was studied using a variety of acidic ion exchange resins as heterogeneous acid catalysts. Quantitative and selective epoxidation of a series of vegetable oils with different composition of saturated, mono-, di- and tri-unsaturated fatty acids was obtained upon identification of the more efficient catalyst and experimental conditions. Furthermore, optimized reaction conditions were successfully applied to the epoxidation of a waste cooking oil, thus extending our procedure to the valorization of a biowaste, an area of increasing importance within a more sustainable society. The use of quantitative HNMR besides making accurate evaluation of the amounts of reagents to be employed and of the selectivity, allowed facile and rapid quantification of mono-, di- and tri-epoxides, thus providing an indirect indication on the fatty acid composition of the vegetable oils, even in the presence of very low quantities of linolenic acid.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36030436b,

title = {Deciphering clinical significance of BCL11A isoforms and protein expression roles in triple-negative breast cancer subtype},

author = {A. Angius and G. Pira and P. Cossu-Rocca and G. Sotgiu and L. Saderi and M. R. Muroni and P. Virdis and D. Piras and R. Vincenzo and C. Carru and D. Coradduzza and M. G. Uras and P. Cottu and A. Fancellu and S. Orrù and P. Uva and M. R. " De Miglio},

url = {https://link.springer.com/article/10.1007/s00432-022-04301-w},

doi = {10.1007/s00432-022-04301-w},

year  = {2022},

date = {2022-08-28},

journal = {J Cancer Res Clin Oncol},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35896539,

title = {Maternal and perinatal obesity induce bronchial obstruction and pulmonary hypertension via IL-6-FoxO1-axis in later life},

author = {J. Selle and K. Dinger and V. Jentgen and D. Zanetti and J. Will and T. Georgomanolis and C. Vohlen and R. Wilke and B. Kojonazarov and O. Klymenko and J. Mohr and S. V Koningsbruggen-Rietschel and C. J. Rhodes and A. Ulrich and D. Hirani and T. Nestler and M. Odenthal and E. Mahabir and S. Nayakanti and S. Dabral and T. Wunderlich and J. Priest and W. Seeger and J. tsch and S. S. Pullamsetti and M. A. Alejandre Alcazar},

year  = {2022},

date = {2022-07-01},

journal = {Nat Commun},

volume = {13},

number = {1},

pages = {4352},

abstract = {s/forced vital capacity ratio Z-score (used as proxy for lung function) and asthma. We conclude that the interleukin-6-FoxO1 pathway in SMC is a molecular mechanism by which perinatal obesity programs the bronchial and vascular structure and function, thereby driving CLD development. Thus, FoxO1 reconstitution provides a potential therapeutic option for preventing this metabolic programming of CLD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fabre2022-znd,

title = {The longitudinal dynamics and natural history of clonal 

 haematopoiesis},

author = {Margarete A Fabre and José Guilherme Almeida and Edoardo Fiorillo and Emily Mitchell and Aristi Damaskou and Justyna Rak and Valeria Orr`u and Michele Marongiu and Michael Spencer Chapman and M S Vijayabaskar and Joanna Baxter and Claire Hardy and Federico Abascal and Nicholas Williams and Jyoti Nangalia and I nigo Martincorena and Peter J Campbell and Eoin F McKinney and Francesco Cucca and Moritz Gerstung and George S Vassiliou},

year  = {2022},

date = {2022-06-01},

journal = {Nature},

volume = {606},

number = {7913},

pages = {335--342},

publisher = {Springer Science and Business Media LLC},

abstract = {Clonal expansions driven by somatic mutations become pervasive 

 across human tissues with age, including in the haematopoietic 

 system, where the phenomenon is termed clonal haematopoiesis1-4. 

 The understanding of how and when clonal haematopoiesis 

 develops, the factors that govern its behaviour, how it 

 interacts with ageing and how these variables relate to 

 malignant progression remains limited5,6. Here we track 697 

 clonal haematopoiesis clones from 385 individuals 55 years of 

 age or older over a median of 13 years. We find that 92.4% of 

 clones expanded at a stable exponential rate over the study 

 period, with different mutations driving substantially different 

 growth rates, ranging from 5% (DNMT3A and TP53) to more than 

 50% per year (SRSF2P95H). Growth rates of clones with the same 

 mutation differed by approximately $pm$5% per year, 

 proportionately affecting slow drivers more substantially. By 

 combining our time-series data with phylogenetic analysis of 

 1,731 whole-genome sequences of haematopoietic colonies from 7 

 individuals from an older age group, we reveal distinct patterns 

 of lifelong clonal behaviour. DNMT3A-mutant clones 

 preferentially expanded early in life and displayed slower 

 growth in old age, in the context of an increasingly competitive 

 oligoclonal landscape. By contrast, splicing gene mutations 

 drove expansion only later in life, whereas TET2-mutant clones 

 emerged across all ages. Finally, we show that mutations driving 

 faster clonal growth carry a higher risk of malignant 

 progression. Our findings characterize the lifelong natural 

 history of clonal haematopoiesis and give fundamental insights 

 into the interactions between somatic mutation, ageing and 

 clonal selection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fabre2022-znc,

title = {The longitudinal dynamics and natural history of clonal 

 haematopoiesis},

author = {Margarete A Fabre and José Guilherme Almeida and Edoardo Fiorillo and Emily Mitchell and Aristi Damaskou and Justyna Rak and Valeria Orr`u and Michele Marongiu and Michael Spencer Chapman and M S Vijayabaskar and Joanna Baxter and Claire Hardy and Federico Abascal and Nicholas Williams and Jyoti Nangalia and I nigo Martincorena and Peter J Campbell and Eoin F McKinney and Francesco Cucca and Moritz Gerstung and George S Vassiliou},

year  = {2022},

date = {2022-06-01},

journal = {Nature},

volume = {606},

number = {7913},

pages = {335--342},

publisher = {Springer Science and Business Media LLC},

abstract = {Clonal expansions driven by somatic mutations become pervasive 

 across human tissues with age, including in the haematopoietic 

 system, where the phenomenon is termed clonal haematopoiesis1-4. 

 The understanding of how and when clonal haematopoiesis 

 develops, the factors that govern its behaviour, how it 

 interacts with ageing and how these variables relate to 

 malignant progression remains limited5,6. Here we track 697 

 clonal haematopoiesis clones from 385 individuals 55 years of 

 age or older over a median of 13 years. We find that 92.4% of 

 clones expanded at a stable exponential rate over the study 

 period, with different mutations driving substantially different 

 growth rates, ranging from 5% (DNMT3A and TP53) to more than 

 50% per year (SRSF2P95H). Growth rates of clones with the same 

 mutation differed by approximately $pm$5% per year, 

 proportionately affecting slow drivers more substantially. By 

 combining our time-series data with phylogenetic analysis of 

 1,731 whole-genome sequences of haematopoietic colonies from 7 

 individuals from an older age group, we reveal distinct patterns 

 of lifelong clonal behaviour. DNMT3A-mutant clones 

 preferentially expanded early in life and displayed slower 

 growth in old age, in the context of an increasingly competitive 

 oligoclonal landscape. By contrast, splicing gene mutations 

 drove expansion only later in life, whereas TET2-mutant clones 

 emerged across all ages. Finally, we show that mutations driving 

 faster clonal growth carry a higher risk of malignant 

 progression. Our findings characterize the lifelong natural 

 history of clonal haematopoiesis and give fundamental insights 

 into the interactions between somatic mutation, ageing and 

 clonal selection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fabre2022-znb,

title = {The longitudinal dynamics and natural history of clonal  haematopoiesis},

author = {Margarete A Fabre and José Guilherme Almeida and Edoardo Fiorillo and Emily Mitchell and Aristi Damaskou and Justyna Rak and Valeria Orr`u and Michele Marongiu and Michael Spencer Chapman and M S Vijayabaskar and Joanna Baxter and Claire Hardy and Federico Abascal and Nicholas Williams and Jyoti Nangalia and I nigo Martincorena and Peter J Campbell and Eoin F McKinney and Francesco Cucca and Moritz Gerstung and George S Vassiliou},

doi = {10.1038/s41586-022-04785-z},

year  = {2022},

date = {2022-06-01},

urldate = {2022-06-01},

journal = {Nature},

volume = {606},

number = {7913},

pages = {335--342},

publisher = {Springer Science and Business Media LLC},

abstract = {Clonal expansions driven by somatic mutations become pervasive 

 across human tissues with age, including in the haematopoietic 

 system, where the phenomenon is termed clonal haematopoiesis1-4. 

 The understanding of how and when clonal haematopoiesis 

 develops, the factors that govern its behaviour, how it 

 interacts with ageing and how these variables relate to 

 malignant progression remains limited5,6. Here we track 697 

 clonal haematopoiesis clones from 385 individuals 55 years of 

 age or older over a median of 13 years. We find that 92.4% of 

 clones expanded at a stable exponential rate over the study 

 period, with different mutations driving substantially different 

 growth rates, ranging from 5% (DNMT3A and TP53) to more than 

 50% per year (SRSF2P95H). Growth rates of clones with the same 

 mutation differed by approximately $pm$5% per year, 

 proportionately affecting slow drivers more substantially. By 

 combining our time-series data with phylogenetic analysis of 

 1,731 whole-genome sequences of haematopoietic colonies from 7 

 individuals from an older age group, we reveal distinct patterns 

 of lifelong clonal behaviour. DNMT3A-mutant clones 

 preferentially expanded early in life and displayed slower 

 growth in old age, in the context of an increasingly competitive 

 oligoclonal landscape. By contrast, splicing gene mutations 

 drove expansion only later in life, whereas TET2-mutant clones 

 emerged across all ages. Finally, we show that mutations driving 

 faster clonal growth carry a higher risk of malignant 

 progression. Our findings characterize the lifelong natural 

 history of clonal haematopoiesis and give fundamental insights 

 into the interactions between somatic mutation, ageing and 

 clonal selection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fabre2022-zn,

title = {The longitudinal dynamics and natural history of clonal 

 haematopoiesis},

author = {Margarete A Fabre and José Guilherme Almeida and Edoardo Fiorillo and Emily Mitchell and Aristi Damaskou and Justyna Rak and Valeria Orr`u and Michele Marongiu and Michael Spencer Chapman and M S Vijayabaskar and Joanna Baxter and Claire Hardy and Federico Abascal and Nicholas Williams and Jyoti Nangalia and I nigo Martincorena and Peter J Campbell and Eoin F McKinney and Francesco Cucca and Moritz Gerstung and George S Vassiliou},

year  = {2022},

date = {2022-06-01},

journal = {Nature},

volume = {606},

number = {7913},

pages = {335--342},

publisher = {Springer Science and Business Media LLC},

abstract = {Clonal expansions driven by somatic mutations become pervasive 

 across human tissues with age, including in the haematopoietic 

 system, where the phenomenon is termed clonal haematopoiesis1-4. 

 The understanding of how and when clonal haematopoiesis 

 develops, the factors that govern its behaviour, how it 

 interacts with ageing and how these variables relate to 

 malignant progression remains limited5,6. Here we track 697 

 clonal haematopoiesis clones from 385 individuals 55 years of 

 age or older over a median of 13 years. We find that 92.4% of 

 clones expanded at a stable exponential rate over the study 

 period, with different mutations driving substantially different 

 growth rates, ranging from 5% (DNMT3A and TP53) to more than 

 50% per year (SRSF2P95H). Growth rates of clones with the same 

 mutation differed by approximately $pm$5% per year, 

 proportionately affecting slow drivers more substantially. By 

 combining our time-series data with phylogenetic analysis of 

 1,731 whole-genome sequences of haematopoietic colonies from 7 

 individuals from an older age group, we reveal distinct patterns 

 of lifelong clonal behaviour. DNMT3A-mutant clones 

 preferentially expanded early in life and displayed slower 

 growth in old age, in the context of an increasingly competitive 

 oligoclonal landscape. By contrast, splicing gene mutations 

 drove expansion only later in life, whereas TET2-mutant clones 

 emerged across all ages. Finally, we show that mutations driving 

 faster clonal growth carry a higher risk of malignant 

 progression. Our findings characterize the lifelong natural 

 history of clonal haematopoiesis and give fundamental insights 

 into the interactions between somatic mutation, ageing and 

 clonal selection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fabre2022-bk,

title = {The longitudinal dynamics and natural history of clonal 

 haematopoiesis},

author = {Margarete A Fabre and José Guilherme Almeida and Edoardo Fiorillo and Emily Mitchell and Aristi Damaskou and Justyna Rak and Valeria Orr`u and Michele Marongiu and Michael Spencer Chapman and M S Vijayabaskar and Joanna Baxter and Claire Hardy and Federico Abascal and Nicholas Williams and Jyoti Nangalia and I nigo Martincorena and Peter J Campbell and Eoin F McKinney and Francesco Cucca and Moritz Gerstung and George S Vassiliou},

year  = {2022},

date = {2022-06-01},

journal = {Nature},

volume = {606},

number = {7913},

pages = {335--342},

publisher = {Springer Science and Business Media LLC},

abstract = {Clonal expansions driven by somatic mutations become pervasive 

 across human tissues with age, including in the haematopoietic 

 system, where the phenomenon is termed clonal haematopoiesis1-4. 

 The understanding of how and when clonal haematopoiesis 

 develops, the factors that govern its behaviour, how it 

 interacts with ageing and how these variables relate to 

 malignant progression remains limited5,6. Here we track 697 

 clonal haematopoiesis clones from 385 individuals 55 years of 

 age or older over a median of 13 years. We find that 92.4% of 

 clones expanded at a stable exponential rate over the study 

 period, with different mutations driving substantially different 

 growth rates, ranging from 5% (DNMT3A and TP53) to more than 

 50% per year (SRSF2P95H). Growth rates of clones with the same 

 mutation differed by approximately $pm$5% per year, 

 proportionately affecting slow drivers more substantially. By 

 combining our time-series data with phylogenetic analysis of 

 1,731 whole-genome sequences of haematopoietic colonies from 7 

 individuals from an older age group, we reveal distinct patterns 

 of lifelong clonal behaviour. DNMT3A-mutant clones 

 preferentially expanded early in life and displayed slower 

 growth in old age, in the context of an increasingly competitive 

 oligoclonal landscape. By contrast, splicing gene mutations 

 drove expansion only later in life, whereas TET2-mutant clones 

 emerged across all ages. Finally, we show that mutations driving 

 faster clonal growth carry a higher risk of malignant 

 progression. Our findings characterize the lifelong natural 

 history of clonal haematopoiesis and give fundamental insights 

 into the interactions between somatic mutation, ageing and 

 clonal selection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Liquid Biopsy in the Oncological Management of a Histologically Undiagnosed Lung Carcinoma: A Case Report},

author = {Giovanni M. Fadda and Renato Lobrano and Milena Casula and Marina Pisano and Antonio Pazzola and Antonio Cossu and Giuseppe Palmieri and Panagiotis Paliogiannis},

year  = {2022},

date = {2022-05-10},

urldate = {2022-05-10},

journal = {Journal of Personalized Medicine },

volume = {12},

number = {1874 },

abstract = {Lung cancer is one of the most common and lethal cancers worldwide. Numerous medications targeting specific molecular alterations in non-small cell lung cancer have been introduced in the last decade and have revolutionized the clinical management of the disease. Their use has brought to a parallel evolution of molecular testing techniques to identify alterations in druggable molecular targets within the genetic material of the tumors. To perform molecular testing biopsy or surgery tissue specimens are needed which in addition allow the histological characterization of the tumors. Unfortunately in real-life practice not all the patients are suitable for biopsy or surgery procedures. The use of liquid biopsy for blood extracted tumoral DNA analysis is a promising approach in unbiopsied cases but it is also weighted by several methodological and technical limitations. We report here a case of histologically undiagnosed lung cancer managed with a liquid biopsy and subsequently with anti-EGFR treatment. Our report highlights that the use of liquid biopsy molecular testing in specific clinical situations can offer treatment opportunities for fragile patients affected by lung cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Landscape of immune-related signatures induced by targeting of different epigenetic regulators in melanoma: implications for immunotherapy},

author = {Anichini Andrea and Molla Alessandra and Nicolini Gabriella and Perotti Valentina Eleonora and Sgambelluri Francesco and Covre Alessia and Fazio Carolina and Lofiego Maria Fortunata and Di Giacomo Anna Maria and Coral Sandra and Manca Antonella and Sini Maria Cristina and Pisano Marina and Noviello Teresa and Caruso Francesca and Brich Silvia and Pruneri Giancarlo and Maurichi Andrea and Santinami Mario and Ceccarelli Michele and Palmieri Giuseppe and Maio Michele and Mortarini Roberta},

url = {https://jeccr.biomedcentral.com/articles/10.1186/s13046-022-02529-5},

year  = {2022},

date = {2022-05-10},

urldate = {2022-05-10},

journal = {JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH},

volume = {41},

number = {325},

abstract = {Background: Improvement of efficacy of immune checkpoint blockade (ICB) remains a major clinical goal. Association of ICB with immunomodulatory epigenetic drugs is an option. However epigenetic inhibitors show a heterogeneous landscape of activities. Analysis of transcriptional programs induced in neoplastic cells by distinct classes of epigenetic drugs may foster identification of the most promising agents.Methods: Melanoma cell lines characterized for mutational and differentiation profile were treated with inhibitors of DNA methyltransferases (guadecitabine) histone deacetylases (givinostat) BET proteins (JQ1 and OTX-015) and enhancer of zeste homolog 2 (GSK126). Modulatory effects of epigenetic drugs were evaluated at the gene and protein levels. Master molecules explaining changes in gene expression were identified by Upstream Regulator (UR) analysis. Gene set enrichment and IPA were used respectively to test modulation of guadecitabine-specific gene and UR signatures in baseline and on-treatment tumor biopsies from melanoma patients in the Phase Ib NIBIT-M4 Guadecitabine + Ipilimumab Trial. Prognostic significance of drug-specific immune-related genes was tested with Timer 2.0 in TCGA tumor datasets.Results: Epigenetic drugs induced different profiles of gene expression in melanoma cell lines. Immune-related genes were frequently upregulated by guadecitabine irrespective of the mutational and differentiation profiles of the melanoma cell lines to a lesser extent by givinostat but mostly downregulated by JQ1 and OTX-015. GSK126 was the least active drug. Quantitative western blot analysis confirmed drug-specific modulatory profiles. Most of the guadecitabine-specific signature genes were upregulated in on-treatment NIBIT-M4 tumor biopsies but not in on-treatment lesions of patients treated only with ipilimumab. A guadecitabine-specific UR signature containing activated molecules of the TLR NF-kB and IFN innate immunity pathways was induced in drug-treated melanoma mesothelioma and hepatocarcinoma cell lines and in a human melanoma xenograft model. Activation of guadecitabine-specific UR signature molecules in on-treatment tumor biopsies discriminated responding from non-responding NIBIT-M4 patients. Sixty-five % of the immune-related genes upregulated by guadecitabine were prognostically significant and conferred a reduced risk in the TCGA cutaneous melanoma dataset.Conclusions: The DNMT inhibitor guadecitabine emerged as the most promising immunomodulatory agent among those tested supporting the rationale for usage of this class of epigenetic drugs in combinatorial immunotherapy approaches.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serra2022-nw,

title = {Comparison of whole blood cryopreservation methods for extensive  flow cytometry immunophenotyping},

author = {Valentina Serra and Valeria Orr`u and Sandra Lai and Monia Lobina and Maristella Steri and Francesco Cucca and Edoardo Fiorillo},

doi = {10.3390/cells11091527},

year  = {2022},

date = {2022-05-01},

urldate = {2022-05-01},

journal = {Cells},

volume = {11},

number = {9},

pages = {1527},

publisher = {MDPI AG},

abstract = {Fresh blood immunophenotyping by flow cytometry, based on the 

 reliable simultaneous detection of several markers in a cell, is 

 the method of choice to study the circulating human immune 

 system. Especially in large and multicenter studies, high sample 

 quality is difficult to achieve, and adequate collection and 

 storage of samples with fine-tuned whole blood cryopreservation 

 is mandatory. Here, we compared the quality of immunophenotypic 

 data obtained from fresh blood with those obtained after five 

 cryopreservation methods by quantifying the levels of 41 immune 

 cell populations. They comprised B and T lymphocyte subsets and 

 their maturation stages, as well as monocytes and granulocytes. 

 Three methods used fixative solutions and two other methods used 

 dimethyl sulfoxide solutions to preserve cell viability. The 

 fixative methods prevented detection of markers critical for 

 identification of B and T cell subsets, including CD27, CXCR3, 

 and CCR6. The other two methods permitted reliable 

 discrimination of most immune-cell populations in thawed 

 samples, though some cell frequencies varied compared to the 

 corresponding fresh sample. Of those two methods, the one 

 preserving blood in media containing dimethyl sulfoxide produced 

 results that were most similar to those with fresh samples.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Liquid Biopsy-Driven Cetuximab Rechallenge Strategy in Molecularly Selected Metastatic Colorectal Cancer Patients},

author = {Stefano Mariani and Marco Puzzoni and Riccardo Giampieri and Pina Ziranu and Valeria Pusceddu and Clelia Donisi and Mara Persano and Giovanna Pinna and Erika Cimbro and Alissa Parrino and Dario Spanu and Andrea Pretta and Eleonora Lai and Nicole Liscia and Alessio Lupi and Enrica Giglio and Grazia Palomba and Milena Casula and Marina Pisano and Giuseppe Palmieri and Mario Scartozzi},

year  = {2022},

date = {2022-04-21},

urldate = {2022-04-21},

journal = {Frontiers in Oncology},

volume = {12},

number = {852583},

abstract = {Background: Rechallenge with EGFR inhibitors represents a promising strategy for patients with RAS wild type (WT) colorectal cancer (CRC) but definitive selection criteria are lacking. Recently the RAS WT status on circulating tumor DNA (ct-DNA) emerged as a potential watershed for this strategy. Our study explored the liquid biopsy-driven cetuximab rechallenge in a RAS and BRAF WT selected population. Methods: CRC patients with RAS and BRAF WT both on tumor tissue and on ct-DNA at baseline receiving rechallenge with cetuximab were eligible for our analysis. Ct-DNA was analyzed for RAS-BRAF mutations with pyro-sequencing and nucleotide sequencing assays. Real-time PCR and droplet digital PCR were performed to confirm the RAS-BRAF mutational status. Results: A total of 26 patients were included in our analysis. In the global population RR was 25.0% median overall survival (mOS) was 5.0 months and median progression-free survival (mPFS) was 3.5 months. Previous response to anti-EGFR was associated with improved mPFS (5.0 vs. 2.0 months HR: 0.26 p = 0.048) and anti-EGFR free interval > 14 months and anti-EGFR free interval > 16 months were associated with improved mPFS (respectively 7.0 vs. 3.0 months HR: 0.27 p = 0.013 and not reached vs. 3.0 months HR: 0.20 p = 0.002) and with improved mOS (respectively 13.0 vs. 5.0 months HR: 0.27 p = 0.013 and 13.0 vs. 5.0 months HR: 0.20 p = 0.002). Previous lines >2 were correlated with improved mPFS (4.0 vs. 1.0 month HR: 0.05 p = 0.041) and with improved mOS (7.0 vs. 1.0 month HR: 0.045 p = 0.034). In a multiple logistic regression model only the anti-EGFR free interval was confirmed to be a significant predictor for mOS and mPFS. Conclusions: Liquid biopsy-driven cetuximab rechallenge was confirmed to be effective. The clinical outcome was consistent with available results from phase II studies. In addition to the molecular selection through the analysis of ct-DNA for RAS the long anti-EGFR free interval is confirmed as a prospective selection criterion for this therapeutic option.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35131881,

title = {Genetic Analysis in African American Children Supports Ancestry-Specific Neuroblastoma Susceptibility},

author = {A. Testori and Z. Vaksman and S. J. Diskin and H. Hakonarson and M. Capasso and A. Iolascon and J. M. Maris and M. Devoto},

year  = {2022},

date = {2022-04-01},

journal = {Cancer Epidemiol Biomarkers Prev},

volume = {31},

number = {4},

pages = {870--875},

abstract = {Neuroblastoma is rarer in African American (AA) children compared with American children of European descent. AA children affected with neuroblastoma, however, more frequently develop the high-risk form of the disease. We have genotyped an AA cohort of 629 neuroblastoma cases (254 high-risk) and 2,990 controls to investigate genetic susceptibility to neuroblastoma in AAs. 10-6 in the EA GWAS, and explained 2% of neuroblastoma risk variance. The significance of the polygenic score dropped rapidly with inclusion of additional SNPs. These findings suggest that several common variants contribute to risk of neuroblastoma in an ancestry-specific fashion. This work supports the need for GWAS to be performed in populations of all races and ethnicities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34605909,

title = {Functional annotation and investigation of the 10q24.33 melanoma risk locus identifies a common variant that influences transcriptional regulation of OBFC1},

author = {A. Cardinale and S. Cantalupo and V. A. Lasorsa and A. Montella and F. Cimmino and M. Succoio and M. Vermeulen and M. P. Baltissen and M. Esposito and M. Avitabile and D. Formicola and A. Testori and F. Bonfiglio and P. Ghiorzo and M. Scalvenzi and F. Ayala and N. Zambrano and M. M. Iles and M. Xu and M. H. Law and K. M. Brown and A. Iolascon and M. Capasso},

year  = {2022},

date = {2022-03-01},

journal = {Hum Mol Genet},

volume = {31},

number = {6},

pages = {863--874},

abstract = {The 10q24.33 locus is known to be associated with susceptibility to cutaneous malignant melanoma (CMM), but the mechanisms underlying this association have been not extensively investigated. We carried out an integrative genomic analysis of 10q24.33 using epigenomic annotations and in vitro reporter gene assays to identify regulatory variants. We found two putative functional single nucleotide polymorphisms (SNPs) in an enhancer and in the promoter of OBFC1, respectively, in neural crest and CMM cells, one, rs2995264, altering enhancer activity. The minor allele G of rs2995264 correlated with lower OBFC1 expression in 470 CMM tumors and was confirmed to increase the CMM risk in a cohort of 484 CMM cases and 1801 controls of Italian origin. Hi-C and chromosome conformation capture (3C) experiments showed the interaction between the enhancer-SNP region and the promoter of OBFC1 and an isogenic model characterized by CRISPR-Cas9 deletion of the enhancer-SNP region confirmed the potential regulatory effect of rs2995264 on OBFC1 transcription. Moreover, the presence of G-rs2995264 risk allele reduced the binding affinity of the transcription factor MEOX2. Biologic investigations showed significant cell viability upon depletion of OBFC1, specifically in CMM cells that were homozygous for the protective allele. Clinically, high levels of OBFC1 expression associated with histologically favorable CMM tumors. Finally, preliminary results suggested the potential effect of decreased OBFC1 expression on telomerase activity in tumorigenic conditions. Our results support the hypothesis that reduced expression of OBFC1 gene through functional heritable DNA variation can contribute to malignant transformation of normal melanocytes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serra2022-br,

title = {Genetic variant within CDK6 regulates immune response to  palbociclib treatment},

author = {Valentina Serra and Valeria Orr`u and Maristella Steri and Edoardo Fiorillo and Francesco Cucca and Magdalena Zoledziewska},

doi = {10.1016/j.clim.2021.108777},

year  = {2022},

date = {2022-02-01},

urldate = {2022-02-01},

journal = {Clin. Immunol.},

volume = {235},

number = {108777},

pages = {108777},

publisher = {Elsevier BV},

abstract = {Everyone carries a set of genetic variants that contribute to 

 regulation of the levels of blood cells, with unknown clinical 

 impact. One of them, rs445 within the cell-cycle checkpoint gene 

 CDK6, reduces the levels of myeloid cell types including 

 granulocytes. We treated CD3+ T cells and whole blood with 

 palbociclib in 41 individuals, who were stratified by genotype 

 for analyses. In T cells we assessed cell cycle and apoptosis, 

 whereas in whole blood, apoptosis in activated (CD11b+), 

 unactivated (CD11b-) granulocytes, cytotoxic (CD8 + CD4-), and 

 helper (CD8-CD4+) T cells. We find that rs445 modulates the 

 immune response of CD8+ T cells. It also increases the level of 

 apoptotic CD11b + activated granulocytes after palbociclib 

 treatment, which, in synergy with neutropenia, may affect drug 

 related adverse events. These results suggest that the effect of 

 palbociclib treatment may depend on underlying genetically 

 encoded individual immune response as well as the direct 

 response to the drug.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35012520,

title = {Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study},

author = {Panagiotis Paliogiannis and Maria Colombino and Maria Cristina Sini and Antonella Manca and Milena Casula and Grazia Palomba and Marina Pisano and Valentina Doneddu and Angelo Zinellu and Davide Santeufemia and and Giovanni Sotgiu and Antonio Cossu and Giuseppe Palmieri},

doi = {10.1186/s12890-021-01803-0},

issn = {1471-2466},

year  = {2022},

date = {2022-01-10},

journal = {BMC Pulm Med},

volume = {22},

number = {1},

pages = {32},

abstract = {BACKGROUND: Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. The aim of this study was to evaluate the global survival in a real-life cohort of patients with LAC harboring driver genetic alterations.



METHODS: A series of 1282 consecutive Sardinian LAC patients who underwent genetic testing from January 2011 through July 2016 was collected. Molecular tests were based on the clinical needs of each single case (EGFR-exon18/19/21, ALK, and, more recently, BRAF-exon15), and the availability of tissue (KRAS, MET, and presence of low-frequency EGFR-T790M mutated alleles at baseline).



RESULTS: The mean follow-up time of the patients was 46 months. EGFR, KRAS, and BRAF mutations were detected in 13.7%, 21.3%, and 3% of tested cases, respectively; ALK rearrangements and MET amplifications were found respectively in 4.7% and 2% of tested cases. As expected, cases with mutations in exons 18-21 of EGFR, sensitizing to anti-EGFR tyrosine kinase inhibitors (TKIs) agents, had a significantly longer survival in comparison to those without (p < 0.0001); conversely, KRAS mutations were associated with a significantly lower survival (p = 0.0058). Among LAC patients with additional tissue section available for next-generation sequencing (NGS)-based analysis, 26/193 (13.5%) patients found positive for even low-rate EGFR-T790M mutated alleles at baseline were associated with a highly significant lower survival in comparison to those without (8.7 vs. 47.4 months, p < 0.0001).



CONCLUSIONS: In addition to its predictive value for addressing targeted therapy approaches, the assessment of as more inclusive mutation analysis at baseline may provide clues about factors significantly impacting on global survival in advanced LAC patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Exploring interaction modes between polysaccharide-based selectors and biologically active 4,4 ′ -bipyridines by experimental and computational analysis. },

author = {Roberto Dallocchio and Alessandro Dessì and Barbara Sechi and Bezhan Chankvetadze and Sergio Cossu and Victor Mamane and Emmanuel Aubert and Carla Rozzo and Giuseppe Palmieri and Ylenia Spissu and Paola Peluso. },

url = {https://irgb.cnr.it/wp-content/uploads/2024/05/Dallocchio-et-al-2022.pdf},

doi = {10.1016/j.jcoa.2022.100030},

issn = {2772-3917},

year  = {2022},

date = {2022-01-06},

urldate = {2022-01-06},

journal = {Journal of Chromatography Open},

volume = {2},

number = {100030},

pages = {1-10},

abstract = {In the last few years, chiral 4,4 ′ -bipyridine derivatives have been developed for different applications in catalysis, enantioseparation science, supramolecular and theoretical chemistry by modulating the activity of the molecu- lar system through the introduction of specific substituents in the heteroaromatic scaffold. More recently, the biological activity of 2 ′ -substituted-3,3 ′ ,5,5 ′ -tetrachloro-2-iodo-4,4 ′ -bipyridines has been explored in the field of transthyretin (TTR) fibrillogenesis inhibition, and the anticancer cytotoxicity of some derivatives is currently under systematic investigation. In this frame, the high-performance liquid chromatography (HPLC) enantiosepa- ration of four atropisomeric 2,2 ′ -disubstituted-4,4 ′ -bipyridines (R, R’ = Ar, I), which contain multiple interaction sites, such as hydrogen bonding (HB) donors and acceptors, halogen bond (XB) donors, and 𝜋-extended electronic clouds, was explored by using n -hexane (Hex)/2-propanol (2-PrOH) 90:10 v/v as a mobile phase (MP), and eight chiral columns with coated and immobilized amylose- and cellulose-based selectors. The impact of subtle struc- tural variations of analytes and selectors on their mutual intermolecular interactivity was evaluated in terms of retention ( k ) and selectivity ( 𝛼) factors. On this basis, chromatographic analysis based on systematic screening of analytes and selectors was integrated with electrostatic potential ( V ) analysis and molecular dynamics (MD) sim- ulations as computational techniques. The effect of temperature on retention, selectivity, and enantiomer elution order (EEO) of the analytes with coated and immobilized amylose tris (3,5-dimethylphenylcarbamate) was also considered by comparing the variation of the thermodynamic profile associated with each enantioseparation. Chromatographic responses proved to be strictly dependent on specific regions within the analyte, and functions of different interactions sites of the analytes as the structure of the chiral selector changes were significantly disclosed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35115688b,

title = {Challenges and future directions for studying effects of host genetics on the gut microbiome},

author = {S. Sanna and A. Kurilshikov and A. Graaf and J. Fu and A. Zhernakova},

url = {https://www.nature.com/articles/s41588-021-00983-z},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nat Genet},

volume = {54},

number = {2},

pages = {100--106},

abstract = {1,000 participants have been published, yet only a few genetic loci have been consistently confirmed across multiple studies. Here we discuss the state of the art for mbGWAS, focusing on current challenges such as the heterogeneity of microbiome measurements and power issues, and we elaborate on potential future directions for genetic analysis of the microbiome.},

note = {[DOI:hrefhttps://dx.doi.org/10.1038/s41588-021-00983-z10.1038/s41588-021-00983-z] [PubMed:hrefhttps://www.ncbi.nlm.nih.gov/pubmed/3278393532783935]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35115690,

title = {Effect of host genetics on the gut microbiome in 7,738 participants of the Đutch Microbiome Project},

author = {E. A. Lopera-Maya and A. Kurilshikov and A. Graaf and S. Hu and S. Andreu-Sánchez and L. Chen and A. V. Vila and R. Gacesa and T. Sinha and V. Collij and M. A. Y. Klaassen and L. A. Bolte and M. F. B. Gois and P. B. T. Neerincx and M. A. Swertz and H. J. M. Harmsen and C. Wijmenga and J. Fu and R. K. Weersma and A. Zhernakova and S. Sanna and R. Aguirre-Gamboa and P. Deelen and L. Franke and J. A. Kuivenhoven and E. A. Lopera-Maya and I. M. Nolte and S. Sanna and H. Snieder and M. A. Swertz and J. M. Vonk and C. Wijmenga},

url = {https://www.nature.com/articles/s41588-021-00992-y},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nat Genet},

volume = {54},

number = {2},

pages = {143--151},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34959343,

title = {Combining Human Genetics of Multiple Sclerosis with Oxidative Stress Phenotype for Đrug Repositioning},

author = {S. Olla and M. Steri and A. Formato and M. B. Whalen and S. Corbisiero and C. Agresti},

year  = {2021},

date = {2021-12-01},

urldate = {2021-12-01},

journal = {Pharmaceutics},

volume = {13},

number = {12},

abstract = {In multiple sclerosis (MS), oxidative stress (OS) is implicated in the neurodegenerative processes that occur from the beginning of the disease. Unchecked OS initiates a vicious circle caused by its crosstalk with inflammation, leading to demyelination, axonal damage and neuronal loss. The failure of MS antioxidant therapies relying on the use of endogenous and natural compounds drives the application of novel approaches to assess target relevance to the disease prior to preclinical testing of new drug candidates. To identify drugs that can act as regulators of intracellular oxidative homeostasis, we applied an in silico approach that links genome-wide MS associations and molecular quantitative trait loci (QTLs) to proteins of the OS pathway. We found 10 drugs with both central nervous system and oral bioavailability, targeting five out of the 21 top-scoring hits, including arginine methyltransferase (CARM1), which was first linked to MS. In particular, the direction of brain expression QTLs for CARM1 and protein kinase MAPK1 enabled us to select BIIB021 and PEITC drugs with the required target modulation. Our study highlights OS-related molecules regulated by functional MS variants that could be targeted by existing drugs as a supplement to the approved disease-modifying treatments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34845919,

title = {Large-Scale Plasma Protein Profiling of Incident Myocardial Infarction, Ischemic Stroke, and Ħeart Failure},

author = {L. Lind and D. Zanetti and M. Ingelsson and S. Gustafsson and J. v and T. L. Assimes},

year  = {2021},

date = {2021-12-01},

journal = {J Am Heart Assoc},

volume = {10},

number = {23},

pages = {e023330},

abstract = {=0.0038). Conclusions Large-scale proteomics seem useful for the discovery of new risk markers for CVD and to improve risk prediction in an elderly population of men. Further studies are needed to replicate the findings in independent samples of both men and women of different ages.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Are Molecular Alterations Linked to Genetic Instability Worth to Be Included as Biomarkers for Directing or Excluding Melanoma Patients to Immunotherapy? },

author = {Giuseppe Palmieri and Carla Maria Rozzo and Maria Colombino and Milena Casula and Maria Cristina Sini and Antonella Manca and Marina Pisano and Valentina Doneddu and Panagiotis Paliogiannis and Antonio Cossu. },

url = {https://irgb.cnr.it/wp-content/uploads/2024/05/Palmieri-et-al-2021-1.pdf},

doi = {doi: 10.3389/fonc.2021.666624},

issn = {2234-943X},

year  = {2021},

date = {2021-05-05},

urldate = {2021-05-05},

journal = {Frontiers in Oncology},

volume = {11},

number = {666624},

pages = {1-11},

abstract = {The improvement of the immunotherapeutic potential in most human cancers, including melanoma, requires the identification of increasingly detailed molecular features underlying the tumor immune responsiveness and acting as disease-associated biomarkers. In recent past years, the complexity of the immune landscape in cancer tissues is being steadily unveiled with a progressive better understanding of the plethora of actors playing in such a scenario, resulting in histopathology diversification, distinct molecular subtypes, and biological heterogeneity. Actually, it is widely recognized that the intracellular patterns of alterations in driver genes and loci may also concur to interfere with the homeostasis of the tumor microenvironment components, deeply affecting the immune response against the tumor. Among others, the different events linked to genetic instability—aneuploidy/somatic copy number alteration (SCNA) or microsatellite instability (MSI)—may exhibit opposite behaviors in terms of immune exclusion or responsiveness.

In this review, we focused on both prevalence and impact of such different types of genetic instability in melanoma in order to evaluate whether their use as biomarkers in an integrated analysis of the molecular profile of such a malignancy may allow defining any potential predictive value for response/resistance to immunotherapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}