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  • 1
    Online Resource
    Online Resource
    Gene Fusion Detection in NSCLC Routine Clinical Practice: Targeted-NGS or FISH?
    MDPI AG ; 2023
    In:  Cells Vol. 12, No. 8 ( 2023-04-11), p. 1135-
    Details
    In: Cells, MDPI AG, Vol. 12, No. 8 ( 2023-04-11), p. 1135-
    Abstract: The ability to identify the broadest range of targetable gene fusions is crucial to facilitate personalized therapy selection for advanced lung adenocarcinoma (LuADs) patients harboring targetable receptor tyrosine kinase (RTK) genomic alterations. In order to evaluate the most effective testing approach for LuAD targetable gene fusion detection, we analyzed 210 NSCLC selected clinical samples, comparing in situ (Fluorescence In Situ Hybridization, FISH, and ImmunoHistoChemistry, IHC) and molecular (targeted RNA Next-Generation Sequencing, NGS, and RealTime-PCR, RT-PCR) approaches. The overall concordance among these methods was high ( 〉 90%), and targeted RNA NGS was confirmed to be the most efficient technique for gene fusion identification in clinical practice, allowing the simultaneous analysis of a large set of genomic rearrangements at the RNA level. However, we observed that FISH was useful to detect targetable fusions in those samples with inadequate tissue material for molecular testing as well as in those few cases whose fusions were not identified by the RNA NGS panel. We conclude that the targeted RNA NGS analysis of LuADs allows accurate RTK fusion detection; nevertheless, standard methods such as FISH should not be dismissed, as they can crucially contribute to the completion of the molecular characterization of LuADs and, most importantly, the identification of patients as candidates for targeted therapies.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells12081135
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
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  • 2
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    An Insight into Gandharan Art: Materials and Techniques of Polychrome Decoration
    MDPI AG ; 2022
    In:  Heritage Vol. 5, No. 1 ( 2022-03-02), p. 488-508
    Details
    In: Heritage, MDPI AG, Vol. 5, No. 1 ( 2022-03-02), p. 488-508
    Abstract: Gandharan art developed in the Himalayan area in the early centuries CE. It has been investigated mostly from an iconographic point of view, missing, until very recently, a systematic technical investigation of materials and techniques. Recently our team began performing chemical analyses of the traces of the polychromy originally covering statues, reliefs and architectural decorations, to discover the ancient painting techniques and artistic technologies. This paper presents the results of the analytical investigation (optical microscopy, Raman spectroscopy and gas chromatography coupled with mass spectrometry) of pigments, ground layers and binders of a new group of samples taken from stucco architectural decorations (2nd–3rd/4th centuries CE). The samples were collected directly at an archaeological site in the Swat Valley, ensuring the exact knowledge of their stratigraphic provenance, as well as the absence of any restoration treatment applied prior sampling. The results are discussed in the wider context of Gandharan polychromy investigated so far by our team, as found in sculptures and architectural decorations preserved in museums (in Italy and France) and in archaeological excavations in Pakistan. The aim of this research is to shed light on the materials and techniques of this Buddhist ancient art from this region and on the influences exerted on it from Eastern and Western artistic traditions.
    Type of Medium: Online Resource
    ISSN: 2571-9408
    URL: Article
    DOI: 10.3390/heritage5010028
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2934573-X
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  • 3
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    Mass Spectrometry-Based Peptide Profiling of Haemolymph from Pterostichus melas Exposed to Pendimethalin Herbicide
    MDPI AG ; 2022
    In:  Molecules Vol. 27, No. 14 ( 2022-07-21), p. 4645-
    Details
    In: Molecules, MDPI AG, Vol. 27, No. 14 ( 2022-07-21), p. 4645-
    Abstract: Pendimethalin-based herbicides are used worldwide for pre-emergence selective control of annual grasses and weeds in croplands. The endurance of herbicides residues in the environment has an impact on the soil biodiversity and fertility, also affecting non-target species, including terrestrial invertebrates. Carabid beetles are known as natural pest control agents in the soil food web of agroecosystems, and feed on invertebrates and weed seeds. Here, a mass spectrometry untargeted profiling of haemolymph is used to investigate Pterostichus melas metabolic response after to pendimethalin-based herbicide exposure. Mass spectrometric data are examined with statistical approaches, such as principal component analysis, for possible correlation with biological effects. Those signals with high correlation are submitted to tandem mass spectrometry to identify the associated biomarker. The time course exposure showed many interesting findings, including a significant downregulation of related to immune and defense peptides (M-lycotoxin-Ls4a, Peptide hormone 1, Paralytic peptide 2, and Serine protease inhibitor 2). Overall, the observed peptide deregulations concur with the general mechanism of uptake and elimination of toxicants reported for Arthropods.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules27144645
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2008644-1
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  • 4
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    Validation of PARADISE 24 and Development of PARADISE-EDEN 36 in Patients with Dementia
    MDPI AG ; 2022
    In:  International Journal of Environmental Research and Public Health Vol. 19, No. 11 ( 2022-06-06), p. 6949-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 11 ( 2022-06-06), p. 6949-
    Abstract: Dementia was one of the conditions focused on in an EU (European Union) project called “PARADISE” (Psychosocial fActors Relevant to brAin DISorders in Europe) that later produced a measure called PARADISE 24, developed within the biopsychosocial model proposed in the International Classification of Functioning Disability and Health (ICF). The aims of this study are to validate PARADISE 24 on a wider sample of patients with mild to moderate dementia to expand PARADISE 24 by defining a more specific scale for dementia, by adding 18 questions specifically selected for dementia, which eventually should be reduced to 12. We enrolled 123 persons with dementia, recruited between July 2017 and July 2019 in home care and long-term care facilities, in Italy, and 80 participants were recruited in Warsaw between January and July 2012 as part of a previous cross-sectional study. The interviews with the patient and/or family were conducted by health professionals alone or as a team by using the Paradise data collection protocol. The psychometric analysis with the Rasch analysis has shown that PARADISE 24 and the selection of 18 additional condition-specific items can be expected to have good measurement properties to assess the functional state in persons with dementia.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph19116949
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175195-X
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  • 5
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    A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 21 ( 2022-10-31), p. 13232-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 21 ( 2022-10-31), p. 13232-
    Abstract: The most frequently used biomarkers to support the diagnosis of Alzheimer’s Disease (AD) are Aβ42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyloid deposition. These tests are rather complex and invasive and not easily applicable to clinical practice. Circulating non-coding RNAs, which are inherently stable and easy to manage, have been reported as promising biomarkers for central nervous system conditions. Recently, circular RNAs (circRNAs) as a novel class of ncRNAs have gained attention. We carried out a pilot study on five participants with AD and five healthy controls (HC) investigating circRNAs by Arraystar Human Circular RNA Microarray V2.0. Among them, 26 circRNAs were differentially expressed (FC ≥ 1.5, p 〈 0.05) in participants with AD compared to HC. From a top 10 of differentially expressed circRNAs, a validation study was carried out on four up-regulated (hsa_circRNA_050263, hsa_circRNA_403959, hsa_circRNA_003022, hsa_circRNA_100837) and two down-regulated (hsa_circRNA_102049, hsa_circRNA_102619) circRNAs in a larger population. Moreover, five subjects with mild cognitive impairment (MCI) were investigated. The analysis confirmed the upregulation of hsa_circRNA_050263, hsa_circRNA_403959, and hsa_circRNA_003022 both in subjects with AD and in MCI compared to HCs. We also investigated all microRNAs potentially interacting with the studied circRNAs. The GO enrichment analysis shows they are involved in the development of the nervous system, and in the cellular response to nerve growth factor stimuli, protein phosphorylation, apoptotic processes, and inflammation pathways, all of which are processes related to the pathology of AD.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232113232
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
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    A Novel Bispecific T-Cell Engager (CD1a x CD3ε) BTCE Is Effective against Cortical-Derived T Cell Acute Lymphoblastic Leukemia (T-ALL) Cells
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 12 ( 2022-06-11), p. 2886-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 12 ( 2022-06-11), p. 2886-
    Abstract: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy burdened by poor prognosis. While huge progress of immunotherapy has recently improved the outcome of B-cell malignancies, the lack of tumor-restricted T-cell antigens still hampers its progress in T-ALL. Therefore, innovative immunotherapeutic agents are eagerly awaited. To this end, we generated a novel asymmetric (2 + 1) bispecific T-cell engager (BTCE) targeting CD1a and CD3ε (CD1a x CD3ε) starting from the development of a novel mAb named UMG2. UMG2 mAb reacts against CD1a, a glycoprotein highly expressed by cortical T-ALL cells. Importantly, no UMG2 binding was found on normal T-cells. CD1a x CD3ε induced high T-cell mediated cytotoxicity against CD1a+ T-ALL cells in vitro, as demonstrated by the concentration-dependent increase of T-cell proliferation, degranulation, induction of cell surface activation markers, and secretion of pro-inflammatory cytokines. Most importantly, in a PBMC-reconstituted NGS mouse model bearing human T-ALL, CD1a x CD3ε significantly inhibited the growth of human T-ALL xenografts, translating into a significant survival advantage of treated animals. In conclusion, CD1a x CD3ε is a novel BTCE highly active against CD1a-expressing cortical-derived T-ALL cells suitable for clinical development as an effective therapeutic option for this rare and aggressive disease.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14122886
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 7
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    Conservation Genetics of Mediterranean Brown Trout in Central Italy (Latium): A Multi-Marker Approach
    MDPI AG ; 2022
    In:  Water Vol. 14, No. 6 ( 2022-03-17), p. 937-
    Details
    In: Water, MDPI AG, Vol. 14, No. 6 ( 2022-03-17), p. 937-
    Abstract: Brown trout is considered a complex of incipient species, including several phylogenetic lineages, whose natural distribution in the Mediterranean area has been altered, since the beginning of the 1900s, by massive introductions of domestic strains of Atlantic origin to support fisheries. Introduced trout naturalize in new suitable environments and extensively hybridize with native populations. Here, we characterized putatively neutral and adaptive genetic variability and population structure of Mediterranean brown trout from six river catchments in central peninsular Italy, as revealed by both mitochondrial (Control Region) and nuclear (microsatellites, LDH-C1, major histocompatibility complex) markers. We quantified the admixture of wild populations with hatchery strains and evaluated the effects of domestic trout introductions on shaping population genetics. Our analyses indicated: (1) a composite picture of genetic variability in the area, with the presence of all native Mediterranean trout mitochondrial lineages (“Adriatic”, “Mediterranean”, “marmoratus”), various frequencies of allochthonous genotypes and different rates of introgression among sampling sites; (2) asymmetric mito-nuclear introgression; (3) increasing nuclear marker diversity with increasing levels of admixture across populations; (4) strong population structure coupled with relatively low effective population size. Data allowed the identification of five management units and we propose specific actions to support ongoing and future conservation strategies within the examined area.
    Type of Medium: Online Resource
    ISSN: 2073-4441
    URL: Article
    DOI: 10.3390/w14060937
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2521238-2
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  • 8
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    Structure and Morphology of Crystalline Syndiotactic Polypropylene-Polyethylene Block Copolymers
    MDPI AG ; 2022
    In:  Polymers Vol. 14, No. 8 ( 2022-04-10), p. 1534-
    Details
    In: Polymers, MDPI AG, Vol. 14, No. 8 ( 2022-04-10), p. 1534-
    Abstract: A study of the structure and morphology of diblock copolymers composed of crystallizable blocks of polyethylene (PE) and syndiotactic polypropylene (sPP) having different lengths is reported. In both analyzed samples, the PE block crystallizes first by cooling from the melt (at 130 °C) and the sPP block crystallizes after at a lower temperature. Small angle X-ray scattering (SAXS) recorded during cooling showed three correlation peaks at values of the scattering vector, q1 = 0.12 nm−1, q2 = 0.24 nm−1 and q3 = 0.4 nm−1, indicating development of a lamellar morphology, where lamellar domains of PE and sPP alternate, each domain containing stacks of crystalline lamellae of PE or sPP sandwiched by their own amorphous phase of PE or sPP. At temperatures higher than 120 °C, when only PE crystals are formed, the morphology is defined by the formation of stacks of PE lamellae (17 nm thick) alternating with amorphous layers and with a long period of nearly 52 nm. At lower temperatures, when crystals of sPP are also well-formed, the morphology is more complex. A model of the morphology at room temperature is proposed based on the correlation distances determined from the self-correlation functions extracted from the SAXS data. Lamellar domains of PE (41.5 nm thick) and sPP (8.2 nm thick) alternate, each domain containing stacks of crystalline lamellae sandwiched by their own amorphous phase, forming a global morphology having a total lamellar periodicity of 49.7 nm, characterized by alternating amorphous and crystalline layers, where the crystalline layers are alternatively made of stacks of PE lamellae (22 nm thick) and thinner sPP lamellae (only 3.5 nm thick).
    Type of Medium: Online Resource
    ISSN: 2073-4360
    URL: Article
    DOI: 10.3390/polym14081534
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527146-5
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  • 9
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    Red Cell Distribution Width and Patient Outcome in Cardiovascular Disease: A ‘’Real-World’’ Analysis
    MDPI AG ; 2021
    In:  Journal of Cardiovascular Development and Disease Vol. 8, No. 10 ( 2021-09-26), p. 120-
    Details
    In: Journal of Cardiovascular Development and Disease, MDPI AG, Vol. 8, No. 10 ( 2021-09-26), p. 120-
    Abstract: Red cell distribution width (RDW) has been shown to predict adverse outcomes in specific scenarios. We aimed to assess the association between RDW and all-cause death and a clinically relevant composite endpoint in a population with various clinical manifestations of cardiovascular diseases. We retrospectively analyzed 700 patients (median age 72.7 years [interquartile range, IQR, 62.6–80]) admitted to the Cardiology ward between January and November 2016. Patients were divided into tertiles according to baseline RDW values. After a median follow-up of 3.78 years (IQR 3.38–4.03), 153 (21.9%) patients died and 247 (35.3%) developed a composite endpoint (all-cause death, acute coronary syndromes, transient ischemic attack/stroke, and/or thromboembolic events). With multivariate Cox regression analysis, the highest RDW tertile was independently associated with an increased risk of all-cause death (adjusted hazard ratio [HR] 2.73, 95% confidence interval [CI] 1.63–4.56) and of the composite endpoint (adjusted HR 2.23, 95% CI 1.53–3.24). RDW showed a good predictive ability for all-cause death (C-statistics: 0.741, 95% CI 0.694–0.788). In a real-world cohort of patients, we found that higher RDW values were independently associated with an increased risk of all-cause death and clinical adverse cardiovascular events thus proposing RDW as a prognostic marker in cardiovascular patients.
    Type of Medium: Online Resource
    ISSN: 2308-3425
    URL: Article
    DOI: 10.3390/jcdd8100120
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2777082-5
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  • 10
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    The Spike Mutants Website: A Worldwide Used Resource against SARS-CoV-2
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 21 ( 2022-10-28), p. 13082-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 21 ( 2022-10-28), p. 13082-
    Abstract: A large number of SARS-CoV-2 mutations in a short period of time has driven scientific research related to vaccines, new drugs, and antibodies to combat the new variants of the virus. Herein, we present a web portal containing the structural information, the tridimensional coordinates, and the molecular dynamics trajectories of the SARS-CoV-2 spike protein and its main variants. The Spike Mutants website can serve as a rapid online tool for investigating the impact of novel mutations on virus fitness. Taking into account the high variability of SARS-CoV-2, this application can help the scientific community when prioritizing molecules for experimental assays, thus, accelerating the identification of promising drug candidates for COVID-19 treatment. Below we describe the main features of the platform and illustrate the possible applications for speeding up the drug discovery process and hypothesize new effective strategies to overcome the recurrent mutations in SARS-CoV-2 genome.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232113082
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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