1,720,971 research outputs found
RICERCA DI BIOMARCATORI NELLE MALATTIE NEUROLOGICHE RARE
No full textSpinal Muscular Atrophy (SMA) is an autosomal recessive disorder due to progressive degeneration of lower motor neurons (LMN) resulting in muscle atrophy and possible respiratory and bulbar involvement. Pathogenic hallmark is the loss of function of Survival Motor Neuron Protein (SMN), encoded by mutated or deleted SMN1 gene. SMN2, the centromeric paralogous gene of SMN1, produces only a small amount of functional SMN (Levin, 2019). Nusinersen is the only disease modifying therapy approved for SMA patients. Neurofilaments light chain (NfL) are intermediate filaments exclusively expressed in neurons. As NfL levels raise following axonal damage, they might be promising diagnostic and prognostic biomarkers in motor neuron diseases (Gaetani, et al., 2019). A different intermediate filament, peripherin (PRPH) assembles with neurofilaments mostly in peripheral neurons and LMN (Zhao, 2016). Human Profilin-1 (PFN-1) is a small actin-binding protein that promotes actin polymerization and has a role in regulating cytoskeletal architecture and dynamics of neurons (Witke, 2004). This study aims to investigate the role of NfL as disease and treatment-response biomarker in a cohort of adult SMA type 2 and 3 patients.
33 SMA type 2 and 3 patients were recruited at the Neuromuscular Center of Padua Hospital, where nusinersen treatment was administered from February 2018 to September 2019 in a loading phase (L1 baseline, L2 day 14, L3 day 28, and L4 day 63) and a maintenance phase (M1-M6, every four months). Cerebrospinal fluid (CSF) samples were collected at each administration; NfL was tested at each time point, additional neurodegeneration biomarkers total tau (t-Tau) and phosphorylated tau (p-Tau) proteins were tested at time points L1 and L3. PFN-1 was tested at each time point as an exploratory muscular biomarker. Further testing of PRPH was conducted at baseline on 20 type 3 patients. NfL concentration was determined with a commercial enzyme-linked immunosorbent assay (ELISA) kit (UmanDiagnostics, Umea, Sweden). T-Tau and pTau were measured with an automated Chemiluminescent Enzyme Immunoassay (CLEIA) analyzer (LUMIPULSE G600 II by Fujirebio, Japan); PFN-1 was measured in serum with a commercial ELISA kit (Cusabio, China); PRPH was tested in serum with a commercial ELISA kit (Abbexa, UK). Both PFN-1 and PRPH results were compared each to a control group of healthy subjects (HC). Neuromuscular outcomes were tested at L1, L4, M1, M2 and M3 with appropriated validated motor scales.
Baseline CSF NfL, t-Tau and p-Tau levels were overall included in the reference ranges for healthy donors. Mean NfL was 211.97 ± 180.9 ng/l in SMA patients, compared to 809.53 ± 1,065.26 ng/l in controls. Correlation was found between baseline log[NfL] and age both in SMA patients and control group. Also log[t-Tau] and log[p-Tau] correlated with log[NfL] at L1, but not at L3, although a slight significant increase was found in t-Tau and p-Tau at L3. NfL significantly increased in loading phase until L3 (mean increase 285.45 ng/l). From L4 NfL started to decrease and no significant difference was found with baseline at M1, M2 and M3. PFN-1 at baseline was higher in SMA than in healthy controls (mean 989 vs 608 ng/l, p=0.0018). PFN-1 showed a complex dynamic during loading phase, with a significant reduction at L4. PRPH was significantly higher compared to HC (median 5.653 μg/l vs 3.168 μg/l, p=0.02). No correlation was found between NfL and motor scores at each time point.
Our study partially reinforces recently published results in similar patients (Wurster, et al., 2019) (Wurster, et al., 2020) (Faravelli, et al., 2020), adding insights on NfL dynamic during the first month of treatment. Neurodegenerative biomarkers might inadequately relate to long disease duration. Serum PFN-1 and PRPH might be more sensitive to reveal LMN damage, therefore subsequent studies are needed to clarify their potential prognostic value.Spinal Muscular Atrophy (SMA) is an autosomal recessive disorder due to progressive degeneration of lower motor neurons (LMN) resulting in muscle atrophy and possible respiratory and bulbar involvement. Pathogenic hallmark is the loss of function of Survival Motor Neuron Protein (SMN), encoded by mutated or deleted SMN1 gene. SMN2, the centromeric paralogous gene of SMN1, produces only a small amount of functional SMN (Levin, 2019). Nusinersen is the only disease modifying therapy approved for SMA patients. Neurofilaments light chain (NfL) are intermediate filaments exclusively expressed in neurons. As NfL levels raise following axonal damage, they might be promising diagnostic and prognostic biomarkers in motor neuron diseases (Gaetani, et al., 2019). A different intermediate filament, peripherin (PRPH) assembles with neurofilaments mostly in peripheral neurons and LMN (Zhao, 2016). Human Profilin-1 (PFN-1) is a small actin-binding protein that promotes actin polymerization and has a role in regulating cytoskeletal architecture and dynamics of neurons (Witke, 2004). This study aims to investigate the role of NfL as disease and treatment-response biomarker in a cohort of adult SMA type 2 and 3 patients.
33 SMA type 2 and 3 patients were recruited at the Neuromuscular Center of Padua Hospital, where nusinersen treatment was administered from February 2018 to September 2019 in a loading phase (L1 baseline, L2 day 14, L3 day 28, and L4 day 63) and a maintenance phase (M1-M6, every four months). Cerebrospinal fluid (CSF) samples were collected at each administration; NfL was tested at each time point, additional neurodegeneration biomarkers total tau (t-Tau) and phosphorylated tau (p-Tau) proteins were tested at time points L1 and L3. PFN-1 was tested at each time point as an exploratory muscular biomarker. Further testing of PRPH was conducted at baseline on 20 type 3 patients. NfL concentration was determined with a commercial enzyme-linked immunosorbent assay (ELISA) kit (UmanDiagnostics, Umea, Sweden). T-Tau and pTau were measured with an automated Chemiluminescent Enzyme Immunoassay (CLEIA) analyzer (LUMIPULSE G600 II by Fujirebio, Japan); PFN-1 was measured in serum with a commercial ELISA kit (Cusabio, China); PRPH was tested in serum with a commercial ELISA kit (Abbexa, UK). Both PFN-1 and PRPH results were compared each to a control group of healthy subjects (HC). Neuromuscular outcomes were tested at L1, L4, M1, M2 and M3 with appropriated validated motor scales.
Baseline CSF NfL, t-Tau and p-Tau levels were overall included in the reference ranges for healthy donors. Mean NfL was 211.97 ± 180.9 ng/l in SMA patients, compared to 809.53 ± 1,065.26 ng/l in controls. Correlation was found between baseline log[NfL] and age both in SMA patients and control group. Also log[t-Tau] and log[p-Tau] correlated with log[NfL] at L1, but not at L3, although a slight significant increase was found in t-Tau and p-Tau at L3. NfL significantly increased in loading phase until L3 (mean increase 285.45 ng/l). From L4 NfL started to decrease and no significant difference was found with baseline at M1, M2 and M3. PFN-1 at baseline was higher in SMA than in healthy controls (mean 989 vs 608 ng/l, p=0.0018). PFN-1 showed a complex dynamic during loading phase, with a significant reduction at L4. PRPH was significantly higher compared to HC (median 5.653 μg/l vs 3.168 μg/l, p=0.02). No correlation was found between NfL and motor scores at each time point.
Our study partially reinforces recently published results in similar patients (Wurster, et al., 2019) (Wurster, et al., 2020) (Faravelli, et al., 2020), adding insights on NfL dynamic during the first month of treatment. Neurodegenerative biomarkers might inadequately relate to long disease duration. Serum PFN-1 and PRPH might be more sensitive to reveal LMN damage, therefore subsequent studies are needed to clarify their potential prognostic value
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
An Abnormal Scattergram of Peripheral Blood Leukocytes Indicative of the Presence of Monoclonal IgM Immunoglobulins
No full textOne disease, different features: COVID-19 laboratory and radiological findings in three Italian patients
Full text linkPossible clinical role of MOG antibody testing in children presenting with acute neurological symptoms
No full textThe differential diagnosis between acquired inflammatory demyelinating syndromes of the central nervous system (CNS), such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and acute disseminated encephalomyelitis (ADEM) can be very challenging at onset. Apart from cerebrospinal fluid oligoclonal bands and anti-aquaporin-4 antibodies (AQP4-Ab), definite diagnostic biomarkers are lacking. Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) have been increasingly described in children with AQP4-seronegative NMOSD, ADEM and other inflammatory demyelinating CND syndromes; despite partial overlaps with AQP4-Ab disease, a novel "MOG-Ab-disorder" phenotype has been suggested. In this study, we tested the presence of MOG-Ab and AQP4-Ab in 57 children at first onset of acute neurological symptoms; three clinical subgroups were identified: 12 patients had acquired inflammatory demyelinating CNS syndromes, 11 had other autoimmune/immune-mediated disorders of the central and peripheral nervous system and 34 had non-immune-mediated CNS disorders. MOG-Abs were found positive only in a subset of cases in the subgroup with acquired inflammatory demyelinating CNS syndromes (in 2/12 patients, both with non-MS phenotype) and in none of the patients with other autoimmune and immune-mediated disorders of the central and peripheral nervous system or with non-immune-mediated disorders of the CNS.Data from the literature review support clinical and analytical observations
Ves-Matic CUBE 200: Is modified Westergren method for erythrocyte sedimentation rate a valid alternative to the gold standard?
No full textDispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
