Metabolomic profiling predicts outcome of rituximab therapy in rheumatoid arthritis.

ObjectiveTo determine whether characterisation of patients' metabolic profiles, utilising nuclear magnetic resonance (NMR) and mass spectrometry (MS), could predict response to rituximab therapy. 23 patients with active, seropositive rheumatoid arthritis (RA) on concomitant methotrexate were treated with rituximab. Patients were grouped into responders and non-responders according to the American College of Rheumatology improvement criteria, at a 20% level at 6 months. A Bruker Avance 700 MHz spectrometer and a Thermo Scientific Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometer were used to acquire (1)H-NMR and ultra high pressure liquid chromatography (UPLC)-MS/MS spectra, respectively, of serum samples before and after rituximab therapy. Data processing and statistical analysis were performed in MATLAB. 14 patients were characterised as responders, and 9 patients were considered non-responders. 7 polar metabolites (phenylalanine, 2-hydroxyvalerate, succinate, choline, glycine, acetoacetate and tyrosine) and 15 lipid species were different between responders and non-responders at baseline. Phosphatidylethanolamines, phosphatidyserines and phosphatidylglycerols were downregulated in responders. An opposite trend was observed in phosphatidylinositols. At 6 months, 5 polar metabolites (succinate, taurine, lactate, pyruvate and aspartate) and 37 lipids were different between groups. The relationship between serum metabolic profiles and clinical response to rituximab suggests that (1)H-NMR and UPLC-MS/MS may be promising tools for predicting response to rituximab

Toward Future Automatic Warehouses: An Autonomous Depalletizing System Based on Mobile Manipulation and 3D Perception

This paper presents a mobile manipulation platform designed for autonomous depalletizing tasks. The proposed solution integrates machine vision, control and mechanical components to increase flexibility and ease of deployment in industrial environments such as warehouses. A collaborative robot mounted on a mobile base is proposed, equipped with a simple manipulation tool and a 3D in-hand vision system that detects parcel boxes on a pallet, and that pulls them one by one on the mobile base for transportation. The robot setup allows to avoid the cumbersome implementation of pick-and-place operations, since it does not require lifting the boxes. The 3D vision system is used to provide an initial estimation of the pose of the boxes on the top layer of the pallet, and to accurately detect the separation between the boxes for manipulation. Force measurement provided by the robot together with admittance control are exploited to verify the correct execution of the manipulation task. The proposed system was implemented and tested in a simplified laboratory scenario and the results of experimental trials are reported

Clinical characteristics of a large cohort of patients with narcolepsy candidate for pitolisant: a cross-sectional study from the Italian PASS Wakix® Cohort

Introduction Narcolepsy is a chronic and rare hypersomnia of central origin characterized by excessive daytime sleepiness and a complex array of symptoms as well as by several medical comorbidities. With growing pharmacological options, polytherapy may increase the possibility of a patient-centered management of narcolepsy symptoms. The aims of our study are to describe a large cohort of Italian patients with narcolepsy who were candidates for pitolisant treatment and to compare patients' subgroups based on current drug prescription (drug-naive patients in whom pitolisant was the first-choice treatment, switching to pitolisant from other monotherapy treatments, and adding on in polytherapy). Methods We conducted a cross-sectional survey based on Italian data from the inclusion visits of the Post Authorization Safety Study of pitolisant, a 5-year observational, multicenter, international study. Results One hundred ninety-one patients were enrolled (76.4% with narcolepsy type 1 and 23.6% with narcolepsy type 2). Most patients (63.4%) presented at least one comorbidity, mainly cardiovascular and psychiatric. Pitolisant was prescribed as an add-on treatment in 120/191 patients (62.8%), as switch from other therapies in 42/191 (22.0%), and as a first-line treatment in 29/191 (15.2%). Drug-naive patients presented more severe sleepiness, lower functional status, and a higher incidence of depressive symptoms. Conclusion Our study presents the picture of a large cohort of Italian patients with narcolepsy who were prescribed with pitolisant, suggesting that polytherapy is highly frequent to tailor a patient-centered approach

Clinical and molecular features of an infant patient affected by Leigh Disease associated to m.14459G > A mitochondrial DNA mutation: a case report

<p>Abstract</p> <p>Background</p> <p>Leigh Syndrome (LS) is a severe neurodegenerative disorder characterized by bilateral symmetrical necrotic lesions in the basal ganglia and brainstem. Onset is in early infancy and prognosis is poor. Causative mutations have been disclosed in mitochondrial DNA and nuclear genes affecting respiratory chain subunits and assembly factors.</p> <p>Case presentation</p> <p>Here we report the clinical and molecular features of a 15-month-old female LS patient. Direct sequencing of her muscle-derived mtDNA revealed the presence of two apparently homoplasmic variants: the novel m.14792C > G and the already known m.14459G > A resulting in p.His16Asp change in cytochrome b (MT-CYB) and p.Ala72Val substitution in ND6 subunit, respectively. The m.14459G > A was heteroplasmic in the mother's blood-derived DNA.</p> <p>Conclusions</p> <p>The m.14459G > A might lead to LS, complicated LS or Leber Optic Hereditary Neuropathy. A comprehensive re-evaluation of previously described 14459G > A-mutated patients does not explain this large clinical heterogeneity.</p

Five carbon- and nitrogen-bearing species in a hot giant planet's atmosphere

The atmospheres of gaseous giant exoplanets orbiting close to their parent stars (hot Jupiters) have been probed for nearly two decades. They allow us to investigate the chemical and physical properties of planetary atmospheres under extreme irradiation conditions. Previous observations of hot Jupiters as they transit in front of their host stars have revealed the frequent presence of water vapour and carbon monoxide in their atmospheres; this has been studied in terms of scaled solar composition under the usual assumption of chemical equilibrium. Both molecules as well as hydrogen cyanide were found in the atmosphere of HD 209458b, a well studied hot Jupiter (with equilibrium temperature around 1,500 kelvin), whereas ammonia was tentatively detected there and subsequently refuted. Here we report observations of HD 209458b that indicate the presence of water (H2O), carbon monoxide (CO), hydrogen cyanide (HCN), methane (CH4), ammonia (NH3) and acetylene (C2H2), with statistical significance of 5.3 to 9.9 standard deviations per molecule. Atmospheric models in radiative and chemical equilibrium that account for the detected species indicate a carbon-rich chemistry with a carbon-to-oxygen ratio close to or greater than 1, higher than the solar value (0.55). According to existing models relating the atmospheric chemistry to planet formation and migration scenarios, this would suggest that HD 209458b formed far from its present location and subsequently migrated inwards. Other hot Jupiters may also show a richer chemistry than has been previously found, which would bring into question the frequently made assumption that they have solar-like and oxygen-rich compositions.Comment: As part of the Springer Nature Content Sharing Initiative, it is possible to access a view-only version of this paper by using the following SharedIt link: https://rdcu.be/cifr

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO

Objectives: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. Methods: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. Results: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). Conclusions: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. Clinical relevance: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients

Ketogenic dietary therapies in epilepsy: recommendations of the Italian League against Epilepsy Dietary Therapy Study Group

A stepwise increase in the utilization of ketogenic dietary therapies for drug-resistant epilepsy has been observed in Italy in the last decade, although it is still considered often underused in many centers when compared to other countries. The Dietary Therapy Study Group of the Italian League against Epilepsy proposes practical recommendations to improve shared knowledge and facilitate the application of ketogenic dietary therapies, optimizing its efficacy and tolerability. The experts involved (11 child neuropsychiatrists, two adult neurologists, one psychologist, one pharmacologist, one pediatric endocrinologist, one representative of patients' associations, and three dietitians and clinical nutritionists) responded to a survey on current clinical practice issues and were asked to discuss controversial topics related to supplementation, long-term maintenance, transition, and a multidisciplinary approach to ketogenic dietary therapies. Practical indications for patient selection, diet initiation, management, side effects prevention, and follow-up are provided

The wide-field, multiplexed, spectroscopic facility WEAVE : survey design, overview, and simulated implementation

Funding for the WEAVE facility has been provided by UKRI STFC, the University of Oxford, NOVA, NWO, Instituto de Astrofísica de Canarias (IAC), the Isaac Newton Group partners (STFC, NWO, and Spain, led by the IAC), INAF, CNRS-INSU, the Observatoire de Paris, Région Île-de-France, CONCYT through INAOE, Konkoly Observatory (CSFK), Max-Planck-Institut für Astronomie (MPIA Heidelberg), Lund University, the Leibniz Institute for Astrophysics Potsdam (AIP), the Swedish Research Council, the European Commission, and the University of Pennsylvania.WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366-959 nm at R ∼ 5000, or two shorter ranges at R ∼ 20,000. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for ∼ 3 million stars and detailed abundances for ∼ 1.5 million brighter field and open-cluster stars; (ii) survey ∼ 0.4 million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey  ∼ 400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in z 1 million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at z > 2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.PostprintPeer reviewe