Validation of Geant4 nuclear reaction models for hadrontherapy and preliminary results with SMF and BLOB

Reliable nuclear fragmentation models are of utmost importance in hadrontherapy, where Monte Carlo (MC) simulations are used to compute the input parameters of the treatment planning software, to validate the deposited dose calculation, to evaluate the biological effectiveness of the radiation, to correlate the bþ emitters production in the patient body with the delivered dose, and to allow a non- invasive treatment verification. Despite of its large use, the models implemented in Geant4 have shown severe limitations in reproducing the measured secondaries yields in ions interaction below 100 MeV/A, in term of production rates, angular and energy distributions [1–3]. We will present a benchmark of the Geant4 models with double-differential cross sec- tion and angular distributions of the secondary fragments produced in the 12C fragmentation at 62 MeV/A on thin carbon target, such a benchmark includes the recently implemented model INCL++ [4,5]. Moreover, we will present the preliminary results, obtained in simulating the same interaction, with SMF [6] and BLOB [7]. Both, SMF and BLOB are semiclassical one-body approaches to solve the Boltzmann-Langevin equation. They include an identical treatment of the mean-field propagation, on the basis of the same effective interaction, but they differ in the way fluctuations are included. In particular, while SMF employs a Uehling-Uhlenbeck collision term and introduces fluctuations as projected on the density space, BLOB introduces fluctuations in full phase space through a modified collision term where nucleon-nucleon correlations are explicitly involved. Both of them, SMF and BLOB, have been developed to sim- ulate the heavy ion interactions in the Fermi-energy regime. We will show their capabilities in describing 12C fragmentation foreseen their implementation in Geant4

Analysis of gut microbiota in rheumatoid arthritis patients. Disease-related dysbiosis and modifications induced by etanercept

A certain number of studies were carried out to address the question of how dysbiosis could affect the onset and development of rheumatoid arthritis (RA), but little is known about the reciprocal influence between microbiota composition and immunosuppressive drugs, and how this interaction may have an impact on the clinical outcome. The aim of this study was to characterize the intestinal microbiota in a groups of RA patients treatment-naïve, under methotrexate, and/or etanercept (ETN). Correlations between the gut microbiota composition and validated immunological and clinical parameters of disease activity were also evaluated. In the current study, a 16S analysis was employed to explore the gut microbiota of 42 patients affected by RA and 10 healthy controls. Disease activity score on 28 joints (DAS-28), erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptides, and dietary and smoking habits were assessed. The composition of the gut microbiota in RA patients free of therapy is characterized by several abnormalities compared to healthy controls. Gut dysbiosis in RA patients is associated with different serological and clinical parameters; in particular, the phylum of Euryarchaeota was directly correlated to DAS and emerged as an independent risk factor. Patients under treatment with ETN present a partial restoration of a beneficial microbiota. The results of our study confirm that gut dysbiosis is a hallmark of the disease, and shows, for the first time, that the anti-tumor necrosis factor alpha (TNF-α) ETN is able to modify microbial communities, at least partially restoring a beneficial microbiota

Time-resolved connectome of the five-factor model of personality

Abstract: The human brain is characterized by highly dynamic patterns of functional connectivity. However, it is unknown whether this time-variant ‘connectome’ is related to the individual differences in the behavioural and cognitive traits described in the five-factor model of personality. To answer this question, inter-network time-variant connectivity was computed in n = 818 healthy people via a dynamical conditional correlation model. Next, network dynamicity was quantified throughout an ad-hoc measure (T-index) and the generalizability of the multi-variate associations between personality traits and network dynamicity was assessed using a train/test split approach. Conscientiousness, reflecting enhanced cognitive and emotional control, was the sole trait linked to stationary connectivity across several circuits such as the default mode and prefronto-parietal network. The stationarity in the ‘communication’ across large-scale networks offers a mechanistic description of the capacity of conscientious people to ‘protect’ non-immediate goals against interference over-time. This study informs future research aiming at developing more realistic models of the brain dynamics mediating personality differences

Comparison between a new thyroglobulin assay with the well-established Beckman Access immunoassay: A preliminary report

Objectives: Measurement of serum thyroglobulin (Tg) plays a key role in the post-thyroidectomy management of differentiated thyroid carcinoma (DTC). In this context, the performance of new-generation thyroglobulin assay has clinical implications in the follow-up of DTC patients. Aim of this study was to compare the new highly sensitive Liaison Tg II (Tg-L) with the well-established Tg Access assay (Tg-A). Materials and methods: A total of 91 residual serum samples (23 positive and 68 negatives for Tg auto-antibodies) were tested by the Beckman Access and Diasorin Liaison assays. Study samples were from 21 patients with pathologically proven DTC and control samples from 70 (16 patients with benign thyroid disease and 54 apparently healthy subjects). Results: Our results showed that Tg-L was highly correlated with Tg-A for both values ranging between 0.2 and 50 ng/mL (Pearson's r = 0.933 [95%CI 0.894-0.958], P <.001) and higher than 50 ng/mL (Pearson's r = 0.849 [95%CI 0.609-0.946], P <.001). For Tg values lower than 0.2 ng/mL, the overall concordance rate was 92%. Moreover, we tested 7 fine-needle aspiration washout fluids (FNA), showing an overall concordance rate in discriminating negative and positive of 100%. Finally, we found no interference by Tg auto-antibodies (TgAbs) for both Tg-L and Tg-A. Conversely, rheumatoid factor (RF) interferes with Tg-A, but not with Tg-L in one patient with no relapsing thyroid carcinoma. Conclusions: Liaison Tg II demonstrated a good correlation with Access Tg assay both for sera and FNAs. Further studies on larger population are needed to evaluate Tg-L clinical impact on DTC patient's follow-up

In-room test results at CNAO of an innovative PT treatments online monitor (Dose Profiler)

The use of C, He and O ions as projectiles in Particle Therapy (PT) treatments is getting more and more widespread as a consequence of their enhanced relative biological effectiveness and oxygen enhancement ratio, when compared to the protons one. The advantages related to the incoming radiation improved efficacy are requiring an accurate online monitor of the dose release spatial distribution. Such monitor is necessary to prevent unwanted damage to the tissues surrounding the tumour that can arise, for example, due to morphological changes occurred in the patient during the treatment with respect to the initial CT scan. PT treatments with ions can be monitored by detecting the secondary radiation produced by the primary beam interactions with the patient body along the path towards the target volume. Charged fragments produced in the nuclear process of projectile fragmentation can be emitted at large angles with respect to the incoming beam direction and can be detected with high efficiency in a nearly background-free environment. The Dose Profiler (DP) detector, developed within the INSIDE project, is a scintillating fibre tracker that allows an online reconstruction and backtracking of such secondary charged fragments. The construction and preliminary in-room tests performed on the DP, carried out using the 12C ions beam of the CNAO treatment centre using an anthropomorphic phantom as a target, will be reviewed in this contribution. The impact of the secondary fragments interactions with the patient body will be discussed in view of a clinical application. Furthermore, the results implications for a pre-clinical trial on CNAO patients, foreseen in 2019, will be discussed

The role of a new class of long noncoding RNAs transcribed from ultraconserved regions in cancer

Ultraconserved regions (UCRs) represent a relatively new class of non-coding genomic sequences highly conserved between human, rat and mouse genomes. These regions can reside within exons of protein-coding genes, despite the vast majority of them localizes within introns or intergenic regions. Several studies have undoubtedly demonstrated that most of these regions are actively transcribed in normal cells/tissues, where they contribute to regulate many cellular processes. Interestingly, these non-coding RNAs exhibit aberrant expression levels in human cancer cells and their expression profiles have been used as prognostic factors in human malignancies, as well as to unambiguously distinguish among distinct cancer types. In this review, we first describe their identification, then we provide some updated information about their genomic localization and classification. More importantly, we discuss about the available literature describing an overview of the mechanisms through which some transcribed UCRs (T-UCR) contribute to cancer progression or to the metastatic spread. To date, the interplay between T-UCRs and microRNAs is the most convincing evidence linking T-UCRs and tumorigenesis. The limitations of these studies and the future challenges to be addressed in order to understand the biological role of T-UCRs are also discussed herein. We envision that future efforts are needed to convincingly include this class of ncRNAs in the growing area of cancer therapeutics

EGFR-Mutationsanalyse beim nichtkleinzelligen Lungenkarzinom: Erfahrungen aus der Routinediagnostik

Zusammenfassung: Hintergrund: Einige Patienten mit einem nichtkleinzelligem Lungenkarzinom (NSCLC) sprechen hervorragend auf Tyrosinkinase-Hemmer (TKI) an. Eine somatische Mutation im epidermalen Wachstumsfaktor-Rezeptor (EGFR) gilt dabei als wichtiger prädikativer Faktor. Patienten und Methode: Wir untersuchten 307 NCSLC auf EGFR-Mutationen (Exone 18-21) und überprüften deren Assoziation mit klinisch-pathologischen Parametern. Ergebnisse: Unter 178 histologischen und 129 zytologischen Tumorproben fanden sich 25 (8,1%) relevante EGFR-Mutationen. Am häufigsten waren Deletionen in Exon19 (50%), gefolgt von der Punktmutation L858R in Exon21 (12,5%). EGFR-Mutationen waren bei Frauen im Vergleich zu Männern (16,8% vs. 2,7%; p<0,001) und in Adenokarzinomen im Vergleich zu den übrigen Karzinomen (11,4% vs. 3,8%; p=0,017) gehäuft. Mutierte NSCLC waren zu 96% TTF-1-positiv. Schlussfolgerung: Therapierelevante EGFR-Mutationen kommen in <10% der mitteleuropäischen NSCLC-Patienten vor und sind gehäuft bei Frauen und TTF-1-positiven Adenokarzinomen. Histologische und zytologische Proben aus der Routinediagnostik sind in gleichem Maße für eine Mutationsanalyse geeigne

Perspective: Cancer Patient Management Challenges During the COVID-19 Pandemic

On March 11, 2020, the WHO has declared the coronavirus disease 2019 (COVID-19) a global pandemic. As the last few months have profoundly changed the delivery of health care in the world, we should recognize the effort of numerous comprehensive cancer centers to share experiences and knowledge to develop best practices to care for oncological patients during the COVID-19 pandemic. Patients as well as physicians must be aware of all these constraints and profound social, personal, and medical challenges posed by the tackling of this deadly disease in everyday life in order to adjust to such a completely novel scenario. This review will discuss facing the challenges and the current approaches that cancer centers in Italy and United States are adopting in order to cope with clinical and research activities

Novel Biological Therapies for Severe Asthma Endotypes

Severe asthma comprises several heterogeneous phenotypes, underpinned by complex pathomechanisms known as endotypes. The latter are driven by intercellular networks mediated by molecular components which can be targeted by specific monoclonal antibodies. With regard to the biological treatments of either allergic or non-allergic eosinophilic type 2 asthma, currently available antibodies are directed against immunoglobulins E (IgE), interleukin-5 (IL-5) and its receptor, the receptors of interleukins-4 (IL-4) and 13 (IL-13), as well as thymic stromal lymphopoietin (TSLP) and other alarmins. Among these therapeutic strategies, the best choice should be made according to the phenotypic/endotypic features of each patient with severe asthma, who can thus respond with significant clinical and functional improvements. Conversely, very poor options so far characterize the experimental pipelines referring to the perspective biological management of non-type 2 severe asthma, which thereby needs to be the focus of future thorough research