Machine-Learning for Prescription Patterns: Random Forest in the Prediction of Dose and Number of Antipsychotics Prescribed to People with Schizophrenia

Objective: We aimed to predict antipsychotic prescription patterns for people with schizophrenia using machine learning (ML) algorithms.Methods: In a cross-sectional design, a sample of community mental health service users (SUs; n = 368) with a primary diagnosis of schizophrenia was randomly selected. Socio-demographic and clinical features, including the number, total dose, and route of administration of the antipsychotic treatment were recorded. Information about the number and the length of psychiatric hospitalization was retrieved. Ordinary Least Square (OLS) regression and ML algorithms (i.e., random forest [RF], supported vector machine, K-nearest neighborhood, and Naive Bayes) were used to estimate the predictors of total antipsychotic dosage and prescription of antipsychotic polytherapy (APP).Results: The strongest predictor of the total dose was APP. The number of Community Mental Health Centers (CMHC) contacts was the most important predictor of APP and, with APP omitted, of dosage. Treatment with anticholinergics predicted APP, emphasizing the strong correlation between APP and higher antipsychotic dose. RF performed better than OLS regression and the other ML algorithms in predicting both antipsychotic dose (root square mean error = 0.70, R-2 = 0.31) and APP (area under the receiving operator curve = 0.66, true positive rate = 0.41, and true negative rate = 0.78).Conclusion: APP is associated with the prescription of higher total doses of antipsychotics. Frequent attenders at CMHCs, and SUs recently hospitalized are often treated with APP and higher doses of antipsychotics. Future prospective studies incorporating standardized clinical assessments for both psychopathological severity and treatment efficacy are needed to confirm these findings

Petrogenesis of Mediterranean lamproites and associated rocks: the role of overprinted metasomatic events in the postcollisional lithospheric upper mantle

High-MgO lamproite and lamproite-like (i.e. lamprophyric) ultrapotassic rocks are recurrent in the Mediterranean and surrounding regions. They are associated in space and time with ultrapotassic shoshonites and high-K calc-alkaline rocks. This magmatism is linked with the geodynamic evolution of the westernmost sector of the Alpine–Himalayan collisional margin, which followed the closure of the Tethys Ocean. Subduc- tion-related lamproites, lamprophyres, shoshonites and high-K calc-alkaline suites were emplaced in the Medi- terranean region in the form of shallow level intrusions (e.g. plugs, dykes and laccoliths) and small volume lava flows, with very subordinate pyroclastic rocks, starting from the Oligocene, in the Western Alps (northern Italy), through the Late Miocene in Corsica (southern France) and in Murcia-Almeria (southeastern Spain), to the Plio- Pleistocene in Southern Tuscany and Northern Latium (central Italy), in the Balkan peninsula (Serbia and Mac- edonia) and in the Western Anatolia (Turkey). The ultrapotassic rocks are mostly lamprophyric, but olivine latitic lavas with a clear lamproitic affinity are also found, as well as dacitic to trachytic differentiated products. Lamp- roite-like rocks range from slightly silica under-saturated to silica over-saturated composition, have relatively low Al2O3, CaO and Na2O contents, resulting in plagioclase-free parageneses, and consist of abundant K-feldspar, phlogopite, diopsidic clinopyroxene and highly forsteritic olivine. Leucite is generally absent, and it is rarely found only in the groundmasses of Spanish lamproites. Mediterranean lamproites and associated rocks share an extreme enrichment in many incompatible trace elements and depletion in High Field Strength Elements and high, and positively correlated Th/La and Sm/La ratios. They have radiogenic Sr and unradiogenic Nd iso- tope compositions, high 207Pb over 206Pb and high time-integrated 232Th/238U. Their composition requires an originally depleted lithospheric mantle source metasomatized by at least two different agents: (1) a high Th/ La and Sm/La (i.e. SALATHO) component deriving from lawsonite-bearing, ancient crustal domains likely hosted in mélanges formed during the diachronous collision of the northward drifting continental slivers from Gondwana; (2) a K-rich component derived from a recent subduction and recycling of siliciclastic sediments. These metasomatic melts produced a lithospheric mantle source characterized by network of felsic and phlogo- pite-rich veins, respectively. Geothermal readjustment during post-collisional events induced progressive melt- ing of the different types of veins and the surrounding peridotite generating the entire compositional spectrum of the observed magmas. In this complex scenario, orogenic Mediterranean lamproites represent rocks that charac- terize areas that were affected by multiple Wilson cycles, as observed in the Alpine–Himalayan Realm

Seroprevalence of Ebola virus infection in Bombali District, Sierra Leone

A serosurvey of anti-Ebola Zaire virus nucleoprotein IgG prevalence was carried out among Ebola virus disease survivors and their Community Contacts in Bombali District, Sierra Leone. Our data suggest that the specie of Ebola virus (Zaire) responsible of the 2013-2016 epidemic in West Africa may cause mild or asymptomatic infection in a proportion of cases, possibly due to an efficient immune response

Beyond BRCA1 and BRCA2: deleterious variants in DNA repair pathway genes in italian families with breast/ovarian and pancreatic cancers

The 5-10% of breast/ovarian cancers (BC and OC) are inherited, and germline pathogenic (P) variants in DNA damage repair (DDR) genes BRCA1 and BRCA2 explain only 10-20% of these cases. Currently, new DDR genes have been related to BC/OC and to pancreatic (PC) cancers, but the prevalence of P variants remains to be explored. The purpose of this study was to investigate the spectrum and the prevalence of pathogenic variants in DDR pathway genes other than BRCA1/2 and to correlate the genotype with the clinical phenotype. A cohort of 113 non-BRCA patients was analyzed by next-generation sequencing using a multigene panel of the 25 DDR pathways genes related to BC, OC, and PC. We found 43 unique variants in 18 of 25 analyzed genes, 14 classified as P/likely pathogenic (LP) and 28 as variants of uncertain significance (VUS). Deleterious variants were identified in 14% of index cases, whereas a VUS was identified in 20% of the probands. We observed a high incidence of deleterious variants in the CHEK2 gene, and a new pathogenic variant was detected in the RECQL gene. These results supported the clinical utility of multigene panel to increase the detection of P/LP carriers and to identify new actionable pathogenic gene variants useful for preventive and therapeutic approaches

Monitoring the last Apennine glacier: recent in situ campaigns and modelling of Calderone glacial apparatus

The Calderone glacier is at present the most southern glacier in Europe (42° 28' 15’’ N). The little apparatus (about 20.000 m2 in surface area) has been giving an interesting response both to short- and long-term climatic variations which resulted in a considerable reduction in surface area and volume. The glacial apparatus is split into two ice bodies (glacierets) since 2000. The two glacierets are located in a deep northward valley below the top of the Corno Grande (2912 m asl) in the centre of the Gran Sasso d’Italia mountain range (Central Italy). Such glacial apparatus has been subjected to a strong reduction, with a loss of total surface area of about 50% and thickness of about 65%with respect to the hypothetical size (about 105.00 m2 and 55 m at the Little Ice Age). Since early 90s the Calderone glacier has been subjected to several multidisciplinary field campaigns to monitor and evaluate its role as an environmental indicator in the framework of global warming. Starting from historical series related to more than a century of records, the variability of the different glacier properties has been estimated by using classical geomorphologic methods as well as in situ and remote sensing techniques. In particular, the last field campaigns, in 2015, 2016 and 2019, have been carried out using Ground Penetrating Radar equipped with different antenna frequencies, drone-based survey, snow pit measurements and chemical-physical sampling. The measurement campaigns have been complemented by a regional climate analysis, spanning the last fifty years, and snowpack modelling initialized with microphysical snow data (e.g., snow density, crystal shape and size, hardness). The snowpack chemical analyses include the main and trace elements, soluble inorganic and organic ions, EC/OC and PAH, with different spatial resolution depending on the analytes. We present here the methodological approach used and some preliminary results

Efficacy and safety of reparixin in patients with severe covid-19 Pneumonia. A phase 3, randomized, double-blind placebo-controlled study

Introduction: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. Methods: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. Results: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. Conclusions: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. Trial registration: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin