Distribution pattern of hepatitis C virus genotypes and correlation with viral load and risk factors in chronic positive patients.

Objective: Hepatitis C virus (HCV) has emerged as a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. The purpose of this study was to describe the distribution pattern of HCV genotypes in chronic hepatitis patients in the Campania region of southern Italy and estimate their association with risk factors and viral load. Materials and Methods: 404 consecutive HCV ribonucleic acid-positive patients were included in the study. HCV genotyping was carried out by the HCV line probe assay test and viral load estimation by the TaqMan real-time PCR system. Results: The predominant genotype was 1 (63.6%), followed by genotype 2 (29.4%), 3 (6.2%) and 4 (0.8%). Subtype 1b was more frequent in females than in males. Conversely, genotype 3 was more frequent in males. No significant difference was observed in age distribution of HCV genotypes. Surgery and dental therapy were the most frequent risk factors for genotype 1 and intravenous drug abuse and tattooing for genotype 3. Patients with genotype 1 more frequently showed high HCV viral load when compared to those with genotypes 2 and 3. Conclusion: The present study revealed that HCV genotypes 1 and 2 accounted for over 95% of all HCV infections in the Campania region, and genotype 1 was more frequently associated with a higher viral load when compared to genotypes 2 and 3

Compound heterozygous missense and deep intronic variants in NDUFAF6 unraveled by exome sequencing and mRNA analysis.

Biallelic mutations in NDUFAF6 have been identified as responsible for cases of autosomal recessive Leigh syndrome associated with mitochondrial complex I deficiency. Here we report two siblings and two unrelated subjects with Leigh syndrome, in which we found the same compound heterozygous missense (c.532G>C:p.A178P) and deep intronic (c.420+784C>T) variants in NDUFAF6. We demonstrated that the identified intronic variant creates an alternative splice site, leading to the production of an aberrant transcript. A detailed analysis of whole-exome sequencing data together with the functional validation based on mRNA analysis may reveal pathogenic variants even in non-exonic regions

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases

Background: Leigh syndrome (LS) is a progressive neurodegenerative disorder associated with primary or secondary dysfunction of mitochondrial oxidative phosphorylation and is the most common mitochondrial disease in childhood. Numerous reports on the biochemical and molecular profiles of LS have been published, but there are limited studies on genetically confirmed large series. We reviewed the clinical, imaging, biochemical and molecular data of 122 patients with a diagnosis of LS collected in the Italian Collaborative Network of Mitochondrial Diseases database. Results: Clinical picture was characterized by early onset of several neurological signs dominated by central nervous system involvement associated with both supra- and sub-tentorial grey matter at MRI in the majority of cases. Extraneurological organ involvement is less frequent in LS than expected for a mitochondrial disorder. Complex I and IV deficiencies were the most common biochemical diagnoses, mostly associated with mutations in SURF1 or mitochondrial-DNA genes encoding complex I subunits. Our data showed SURF1 as the genotype with the most unfavorable prognosis, differently from other cohorts reported to date. Conclusion: We report on a large genetically defined LS cohort, adding new data on phenotype-genotype correlation, prognostic factors and possible suggestions to diagnostic workup

Encephalopathies with intracranial calcification in children: Clinical and genetic characterization

none42noBackground: We present a group of patients affected by a paediatric onset genetic encephalopathy with cerebral calcification of unknown aetiology studied with Next Generation Sequencing (NGS) genetic analyses. Methods: We collected all clinical and radiological data. DNA samples were tested by means of a customized gene panel including fifty-nine genes associated with known genetic diseases with cerebral calcification. Results: We collected a series of fifty patients. All patients displayed complex and heterogeneous phenotypes mostly including developmental delay and pyramidal signs and less frequently movement disorder and epilepsy. Signs of cerebellar and peripheral nervous system involvement were occasionally present. The most frequent MRI abnormality, beside calcification, was the presence of white matter alterations; calcification was localized in basal ganglia and cerebral white matter in the majority of cases. Sixteen out of fifty patients tested positive for mutations in one of the fifty-nine genes analyzed. In fourteen cases the analyses led to a definite genetic diagnosis while results were controversial in the remaining two. Conclusions: Genetic encephalopathies with cerebral calcification are usually associated to complex phenotypes. In our series, a molecular diagnosis was achieved in 32% of cases, suggesting that the molecular bases of a large number of disorders are still to be elucidated. Our results confirm that cerebral calcification is a good criterion to collect homogeneous groups of patients to be studied by exome or whole genome sequencing; only a very close collaboration between clinicians, neuroradiologists and geneticists can provide better results from these new generation molecular techniques.noneTonduti D.; Panteghini C.; Pichiecchio A.; Decio A.; Carecchio M.; Reale C.; Moroni I.; Nardocci N.; Campistol J.; Garcia-Cazorla A.; Perez Duenas B.; Zorzi G.; Ardissone A.; Granata T.; Freri E.; Zibordi F.; Ragona F.; D'Arrigo S.; Saletti V.; Esposito S.; Pantaleoni C.; Riva D.; De Giorgis V.; Cereda C.; Valente M.L.; Sproviero D.; Poo Arguelles M.P.; Estupina C.F.; Sans Fito A.M.; Martorell Sampol L.; Del Mar O'Callaghan Gordo M.; Ortez Gonzalez C.I.; Gonzalez Alvarez V.; Garcia-Segarra N.; Fusco C.; Bertini E.; Diodato D.; Fazzi E.; Galli J.; Chiapparini L.; Garavaglia B.; Orcesi S.Tonduti, D.; Panteghini, C.; Pichiecchio, A.; Decio, A.; Carecchio, M.; Reale, C.; Moroni, I.; Nardocci, N.; Campistol, J.; Garcia-Cazorla, A.; Perez Duenas, B.; Zorzi, G.; Ardissone, A.; Granata, T.; Freri, E.; Zibordi, F.; Ragona, F.; D'Arrigo, S.; Saletti, V.; Esposito, S.; Pantaleoni, C.; Riva, D.; De Giorgis, V.; Cereda, C.; Valente, M. L.; Sproviero, D.; Poo Arguelles, M. P.; Estupina, C. F.; Sans Fito, A. M.; Martorell Sampol, L.; Del Mar O'Callaghan Gordo, M.; Ortez Gonzalez, C. I.; Gonzalez Alvarez, V.; Garcia-Segarra, N.; Fusco, C.; Bertini, E.; Diodato, D.; Fazzi, E.; Galli, J.; Chiapparini, L.; Garavaglia, B.; Orcesi, S

Movement disorders in children with a mitochondrial disease: A cross-sectional survey from the nationwide italian collaborative network of mitochondrial diseases

none41noMovement disorders are increasingly being recognized as a manifestation of childhood-onset mitochondrial diseases (MDs). However, the spectrum and characteristics of these conditions have not been studied in detail in the context of a well-defined cohort of patients. We retrospectively explored a cohort of individuals with childhood-onset MDs querying the Nationwide Italian Collaborative Network of Mitochondrial Diseases database. Using a customized online questionnaire, we attempted to collect data from the subgroup of patients with movement disorders. Complete information was available for 102 patients. Movement disorder was the presenting feature of MD in 45 individuals, with a mean age at onset of 11 years. Ataxia was the most common movement disorder at onset, followed by dystonia, tremor, hypokinetic disorders, chorea, and myoclonus. During the disease course, most patients (67.7%) encountered a worsening of their movement disorder. Basal ganglia involvement, cerebral white matter changes, and cerebellar atrophy were the most commonly associated neuroradiological patterns. Forty-one patients harbored point mutations in the mitochondrial DNA, 10 carried mitochondrial DNA rearrangements, and 41 cases presented mutations in nuclear-DNA-encoded genes, the latter being associated with an earlier onset and a higher impairment in activities of daily living. Among our patients, 32 individuals received pharmacological treatment; clonazepam and oral baclofen were the most commonly used drugs, whereas levodopa and intrathecal baclofen administration were the most effective. A better delineation of the movement disorders phenotypes starting in childhood may improve our diagnostic workup in MDs, fine tuning management, and treatment of affected patients.mixedTicci C.; Orsucci D.; Ardissone A.; Bello L.; Bertini E.; Bonato I.; Bruno C.; Carelli V.; Diodato D.; Doccini S.; Donati M.A.; Dosi C.; Filosto M.; Fiorillo C.; La Morgia C.; Lamperti C.; Marchet S.; Martinelli D.; Minetti C.; Moggio M.; Mongini T.E.; Montano V.; Moroni I.; Musumeci O.; Pancheri E.; Pegoraro E.; Primiano G.; Procopio E.; Rubegni A.; Scalise R.; Sciacco M.; Servidei S.; Siciliano G.; Simoncini C.; Tolomeo D.; Tonin P.; Toscano A.; Tubili F.; Mancuso M.; Battini R.; Santorelli F.M.Ticci, C.; Orsucci, D.; Ardissone, A.; Bello, L.; Bertini, E.; Bonato, I.; Bruno, C.; Carelli, V.; Diodato, D.; Doccini, S.; Donati, M. A.; Dosi, C.; Filosto, M.; Fiorillo, C.; La Morgia, C.; Lamperti, C.; Marchet, S.; Martinelli, D.; Minetti, C.; Moggio, M.; Mongini, T. E.; Montano, V.; Moroni, I.; Musumeci, O.; Pancheri, E.; Pegoraro, E.; Primiano, G.; Procopio, E.; Rubegni, A.; Scalise, R.; Sciacco, M.; Servidei, S.; Siciliano, G.; Simoncini, C.; Tolomeo, D.; Tonin, P.; Toscano, A.; Tubili, F.; Mancuso, M.; Battini, R.; Santorelli, F. M

Soil erosion modelling: a global review and statistical analysis

To gain a better understanding of the global application of soil erosion prediction models, we comprehensively reviewed relevant peer-reviewed research literature on soil-erosion modelling published between 1994 and 2017. We aimed to identify (i) the processes and models most frequently addressed in the literature, (ii) the regions within which models are primarily applied, (iii) the regions which remain unaddressed and why, and (iv) how frequently studies are conducted to validate/evaluate model outcomes relative to measured data. To perform this task, we combined the collective knowledge of 67 soil-erosion scientists from 25 countries. The resulting database, named ‘Global Applications of Soil Erosion Modelling Tracker (GASEMT)’, includes 3030 individual modelling records from 126 countries, encompassing all continents (except Antarctica). Out of the 8471 articles identified as potentially relevant, we reviewed 1697 appropriate articles and systematically evaluated and transferred 42 relevant attributes into the database. This GASEMT database provides comprehensive insights into the state-of-the-art of soil- erosion models and model applications worldwide. This database intends to support the upcoming country-based United Nations global soil-erosion assessment in addition to helping to inform soil erosion research priorities by building a foundation for future targeted, in-depth analyses. GASEMT is an open-source database available to the entire user-community to develop research, rectify errors, and make future expansions.</p

Soil erosion modelling: a bibliometric analysis

Soil erosion can present a major threat to agriculture due to loss of soil, nutrients, and organic carbon. Therefore, soil erosion modelling is one of the steps used to plan suitable soil protection measures and detect erosion hotspots. A bibliometric analysis of this topic can reveal research patterns and soil erosion modelling characteristics that can help identify steps needed to enhance the research conducted in this field. Therefore, a detailed bibliometric analysis, including investigation of collaboration networks and citation patterns, should be conducted. The updated version of the Global Applications of Soil Erosion Modelling Tracker (GASEMT) database contains information about citation characteristics and publication type. Here, we investigated the impact of the number of authors, the publication type and the selected journal on the number of citations. Generalized boosted regression tree (BRT) modelling was used to evaluate the most relevant variables related to soil erosion modelling. Additionally, bibliometric networks were analysed and visualized. This study revealed that the selection of the soil erosion model has the largest impact on the number of publication citations, followed by the modelling scale and the publication's CiteScore. Some of the other GASEMT database attributes such as model calibration and validation have negligible influence on the number of citations according to the BRT model. Although it is true that studies that conduct calibration, on average, received around 30% more citations, than studies where calibration was not performed. Moreover, the bibliographic coupling and citation networks show a clear continental pattern, although the co-authorship network does not show the same characteristics. Therefore, soil erosion modellers should conduct even more comprehensive review of past studies and focus not just on the research conducted in the same country or continent. Moreover, when evaluating soil erosion models, an additional focus should be given to field measurements, model calibration, performance assessment and uncertainty of modelling results. The results of this study indicate that these GASEMT database attributes had smaller impact on the number of citations, according to the BRT model, than anticipated, which could suggest that these attributes should be given additional attention by the soil erosion modelling community. This study provides a kind of bibliographic benchmark for soil erosion modelling research papers as modellers can estimate the influence of their paper