Deconvolution of 1D NMR spectra: A deep learning-based approach.

The analysis of nuclear magnetic resonance (NMR) spectra to detect peaks and characterize their parameters, often referred to as deconvolution, is a crucial step in the quantification, elucidation, and verification of the structure of molecular systems. However, deconvolution of 1D NMR spectra is a challenge for both experts and machines. We propose a robust, expert-level quality deep learning-based deconvolution algorithm for 1D experimental NMR spectra. The algorithm is based on a neural network trained on synthetic spectra. Our customized pre-processing and labeling of the synthetic spectra enable the estimation of critical peak parameters. Furthermore, the neural network model transfers well to the experimental spectra and demonstrates low fitting errors and sparse peak lists in challenging scenarios such as crowded, high dynamic range, shoulder peak regions as well as broad peaks. We demonstrate in challenging spectra that the proposed algorithm is superior to expert results.

Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario.

INTRODUCTION: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. METHODS: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS: A slight reduction (-6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop -12% versus -3.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). CONCLUSIONS: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts.

Anodal transcranial direct current stimulation in chronic migraine and medication overuse headache: A pilot double-blind randomized sham-controlled trial.

OBJECTIVES: Little evidence is available on the role of transcranial direct current stimulation (tDCS) in patients affected by chronic migraine (CM) and medication overuse headache (MOH). We aim to investigate the effects of tDCS in patients with CM and MOH as well as its role on brain activity. METHODS: Twenty patients with CM and MOH were hospitalized for a 7-day detoxification treatment. Upon admission, patients were randomly assigned to anodal tDCS or sham stimulation delivered over the primary motor cortex contralateral to the prevalent migraine pain side every day for 5 days. Clinical data were recorded at baseline (T0), after 1 month (T2) and 6 months (T3). EEG recording was performed at T0, at the end of the tDCS/Sham treatment, and at T2. RESULTS: At T2 and T3, we found a significant reduction in monthly migraine days (p = 0.001), which were more pronounced in the tDCS group when compared to the sham group (p = 0.016). At T2, we found a significant increase of alpha rhythm in occipital leads, which was significantly higher in tDCS group when compared to sham group. CONCLUSIONS: tDCS showed adjuvant effects to detoxification in the management of patients with CM and MOH. The EEG recording showed a significant potentiation of alpha rhythm, which may represent a correlate of the underlying changes in cortico-thalamic connections. SIGNIFICANCE: This study suggests a possible role for tDCS in the treatment of CM and MOH. The observed clinical improvement is coupled with a potentiation of EEG alpha rhythm.

The network integration of epileptic activity in relation to surgical outcome.

OBJECTIVE: Epilepsy is a network disease with epileptic activity and cognitive impairment involving large-scale brain networks. A complex network is involved in the seizure and in the interictal epileptiform discharges (IEDs). Directed connectivity analysis, describing the information transfer between brain regions, and graph analysis are applied to high-density EEG to characterise networks. METHODS: We analysed 19 patients with focal epilepsy who had high-density EEG containing IED and underwent surgery. We estimated cortical activity during IED using electric source analysis in 72 atlas-based cortical regions of the individual brain MRI. We applied directed connectivity analysis (information Partial Directed Coherence) and graph analysis on these sources and compared patients with good vs poor post-operative outcome at global, hemispheric and lobar level. RESULTS: We found lower network integration reflected by global, hemispheric, lobar efficiency during the IED (p < 0.05) in patients with good post-surgical outcome, compared to patients with poor outcome. Prediction was better than using the IED field or the localisation obtained by electric source imaging. CONCLUSIONS: Abnormal network patterns in epilepsy are related to seizure outcome after surgery. SIGNIFICANCE: Our finding may help understand networks related to a more "isolated" epileptic activity, limiting the extent of the epileptic network in patients with subsequent good post-operative outcome.

Estimating EEG Source Dipole Orientation Based on Singular-value Decomposition for Connectivity Analysis.

In the last decade, the use of high-density electrode arrays for EEG recordings combined with the improvements of source reconstruction algorithms has allowed the investigation of brain networks dynamics at a sub-second scale. One powerful tool for investigating large-scale functional brain networks with EEG is time-varying effective connectivity applied to source signals obtained from electric source imaging. Due to computational and interpretation limitations, the brain is usually parcelled into a limited number of regions of interests (ROIs) before computing EEG connectivity. One specific need and still open problem is how to represent the time- and frequency-content carried by hundreds of dipoles with diverging orientation in each ROI with one unique representative time-series. The main aim of this paper is to provide a method to compute a signal that explains most of the variability of the data contained in each ROI before computing, for instance, time-varying connectivity. As the representative time-series for a ROI, we propose to use the first singular vector computed by a singular-value decomposition of all dipoles belonging to the same ROI. We applied this method to two real datasets (visual evoked potentials and epileptic spikes) and evaluated the time-course and the frequency content of the obtained signals. For each ROI, both the time-course and the frequency content of the proposed method reflected the expected time-course and the scalp-EEG frequency content, representing most of the variability of the sources (~ 80%) and improving connectivity results in comparison to other procedures used so far. We also confirm these results in a simulated dataset with a known ground truth.

The changing scenario of 1st line therapy in non-oncogene addicted NSCLCs in the era of immunotherapy.

During the last two decades front-line treatment of metastatic Non Small Cell Lung Cancer (NSCLC) has profoundly changed moving from the old "one size fits all" concept to a "histology-based" approach and then, for a small subgroup of patients to a "molecularly-selected" one. The development of immune checkpoint inhibitors and the unprecedented results reported in 2nd/3rd line prompted the evaluation of these novel therapeutic agents in chemotherapy-naïve patients either alone or in combination with platinum-based chemotherapy. Several randomized trials are evaluating the impact of immune-checkpoint inhibitors in 1st line and some of them have yet produced preliminary evidence of efficacy. However, still a long way to go and several questions are still unanswered, including proper patients selection, optimal sequential/combinatorial use of these agents, appropriate treatment duration, and finally the identification of predictive biomarkers. The aim of this paper is to provide a comprehensive overview on the growing role of immune checkpoint inhibitors in the upfront treatment of advanced non-oncogene addicted NSCLC either as single agent or in combination with other agents.

Deoxygenation of waste cooking oil and non-edible oil for the production of liquid hydrocarbon biofuels.

Deoxygenation of waste cooking vegetable oil and Jatropha curcas oil under nitrogen atmosphere was performed in batch and semi-batch experiments using CaO and treated hydrotalcite (MG70) as catalysts at 400 °C. In batch conditions a single liquid fraction (with yields greater than 80 wt.%) was produced containing a high proportion of hydrocarbons (83%). In semi-batch conditions two liquid fractions (separated by a distillation step) were obtained: a light fraction and an intermediate fraction containing amounts of hydrocarbons between 72-80% and 85-88% respectively. In order to assess the possible use of the liquid products as alternative fuels a complete chemical characterization and measurement of their properties were carried out.

Post-transplant Lymphoproliferative Disorders: A Rare Case of Primary Pericardial Involvement Epstein-Barr Virus-Correlated in Heart Transplantation.

Post-transplant lymphoproliferative disorders (PTLDs) are considered a fatal consequence of immunosuppression. We report a case of a 52-year-old patient, who underwent a cardiac transplantation and presented undefined recurrent episodes of pleuropericardial effusions without lymphoadenomegaly at chest radiographs and computed tomography. Histopathological analysis of the bioptic pericardium showed a specific chronic inflammation. Monitoring endomyocardial biopsies (EMBs) showed only 1 episodes of greater than grade 2R acute cellular rejection requiring immunosuppressive treatment, mild vasculitis in 2 subsequently EMBs while constantly negative for antibody-mediated rejection or infection. Only a post-mortem examination demonstrated the presence of an aggressive acute non-Epstein-Barr virus (EBV)-related proliferative disorder with unusual primitive localization into the pericardium and with coronary epicardial and intramyocardial necrotizing vasculitis and superimposed occlusive and subocclusive thrombosis. Recurrence of unexplained early pleuropericardial effusion and mild intramyocardial vasculitis should raise the suspicion of PTLD requiring reduction of immunosuppression, even in the setting of negative intramyocardial cellular infiltrate and tissue EBV-negative molecular assessment.

HLA-DRB1 typing by micro-bead array assay identifies the origin of early lymphoproliferative disorder in a heart transplant recipient.

We report the case of a 68-year-old woman who underwent heart transplantation for hypertrophic cardiomyopathy. Two months after the transplant she developed mild fever and dyspnea with a marked drop in left ventricle ejection fraction of 31%. Coronary angiography was negative for cardiac allograft vasculopathy. Endomyocardial biopsy revealed ischemic damage with no evidence of acute cellular rejection, antibody-mediated rejection or viral myocarditis. A neoplastic process was suspected even though full-body computerized tomography was negative for malignancy. The patient died 4 months after transplantation. The autopsy showed acute antero-septal myocardial infarction due to a nodular epicardial EBV-related posttransplant lymphoproliferative disorder (PTLD) infiltrating the left anterior descending coronary artery with occlusive neoplastic thrombosis. We highlight two major aspects of this case: (1) the unusual occurrence of early PTLD involving the cardiac allograft and causing a fatal outcome, (2) the application of an immunological technique for HLA-DRB1 typing to posttransplant paraffin-embedded autopsy material to identify the recipient origin of this early malignancy, thus excluding a possible donor-transmitted neoplasm.

Surface-enhanced Raman spectroscopy: nonlocal limitations.

Giant field enhancement and field singularities are a natural consequence of the commonly employed local-response framework. We show that a more general nonlocal treatment of the plasmonic response leads to new and possibly fundamental limitations on field enhancement with important consequences for our understanding of surface-enhanced Raman spectroscopy (SERS). The intrinsic length scale of the electron gas serves to smear out assumed field singularities, leaving the SERS enhancement factor finite, even for geometries with infinitely sharp features. For silver nanogroove structures, mimicked by periodic arrays of half-cylinders (up to 120 nm in radius), we find no enhancement factors exceeding 10 orders of magnitude (10(10)).

Distribution and seasonal variability of trace elements in atmospheric particulate in the Venice Lagoon.

Size distribution and selected element concentrations of atmospheric particulate matter (PM) were investigated in the Venice Lagoon, at three sites characterised by different anthropogenic influence. The PM(10) samples were collected in six size fractions (10-7.2, 7.2-3.0, 3.0-1.5, 1.5-0.95; 0.95-0.49 and <0.49 µm) with high volume cascade impactors, and the concentration of 17 elements (Al, As, Ca, Cd, Co, Cu, Fe, K, Li, Mg, Mn, Na, Ni, Pb, Sr, V, Zn) was determined by inductively coupled plasma quadrupole mass spectroscopy. More than 1 year of sampling activities allowed the examination of seasonal variability in size distribution of atmospheric particulates and element contents for each site. At all the stations, particles with an aerodynamic diameter <3 µm were predominant, thus accounting for more than 78% of the total aerosol mass concentration. The highest PM(10) concentrations for almost all elements were found at the site which is more influenced by industrial and urban emissions. Similarity in size distribution of elements at all sites allowed the identification of three main behavioural types: (a) elements found mainly within coarse particles (Ca, Mg, Na, Sr); (b) elements found mainly within fine particles (As, Cd, Ni, Pb, V) and (c) elements with several modes spread throughout the entire size range (Co, Cu, Fe, K, Zn, Mn). Factor Analysis was performed on aerosol data separately identified as fine and coarse types in order to examine the relationships between the inorganic elements and to identify their origin. Multivariate statistical analysis and assessment of similarity in the size distribution led to similar conclusions on the sources.

A single question for the rapid screening of restless legs syndrome in the neurological clinical practice.

The purposes of this study were to validate the use of a single standard question for the rapid screening of restless legs syndrome (RLS) and to analyze the eventual effects of the presence of RLS on self-assessed daytime sleepiness, global clinical severity and cognitive functioning. We evaluated a group of 521 consecutive patients who accessed our neurology clinic for different reasons. Beside the answer to the single question and age, sex, and clinical diagnosis, the following items were collected from all patients and normal controls: the four criteria for RLS, the Epworth Sleepiness Scale (ESS), the Clinical Global Impression of Severity (CGI-S), and the Mini-Mental State evaluation. RLS was found in 112 patients (70 idiopathic). The single question had 100% sensitivity and 96.8% specificity for the diagnosis of RLS. ESS and CGI-S were significantly higher in both RLS patient groups than in normal controls. RLS severity was significantly higher in idiopathic than in associated/symptomatic RLS patients. RLS can be screened with high sensitivity and good reliability in large patient groups by means of the single question; however, the final diagnosis should always be confirmed by the diagnostic features of RLS and accompanied by a careful search for comorbid conditions.

Low total cholesterol predicts mortality in the nondemented oldest old.

Several studies have demonstrated the importance of hypercholesterolemia as a cardiovascular risk factor and a direct correlation between the reduction in cholesterolemia and the reduction in cardiovascular mortality in populations younger than 65 years. This correlation is controversial in the elderly and, particularly, in the oldest old. The aim of our study was to evaluate the total cholesterol in the oldest old and to assess the eventual presence of correlation between total cholesterol levels and mortality in a group of nondemented oldest old. A subsample of 40 subjects was extracted from the 103 subjects aged over 84 years living in Troina, a rural village in Sicily. We excluded all subjects under therapy with lipid-lowering drugs, demented, with malnutrition or affected by acute or chronic diseases which might cause death in the short term. At the end, 23 subjects (15 males and 8 females) were included in the study. After 2 years, mortality data of all subjects included in the study were obtained from official registers. The statistical analysis was performed by means of the X(2) test. In all subjects the mean of total cholesterol was of 182+/-32 mg/dl (mean+/-SD) and the body mass index was above 20; 17 subjects were in the normal range, 3 were moderately over-weighed and 3 were severely over-weighed. Overall, mortality rate after 2 years was 30% (7 subjects, 4 males and 3 females). We evaluated the relationship between mortality and 4 factors: sex, age, body mass index (BMI) and serum total cholesterol. Mortality was significantly correlated (p<0.002) only with a low level of total serum cholesterol

Trace metals in aerosol at Terra Nova Bay, Antarctica.

Atmospheric particulate with an aerodynamic diameter <10 microm (PM10) was sampled continuously during the austral summers of 2000-2001 and 2001-2002 at a coastal site near to the Italian base of Terra Nova, Antarctica. Li, Pb, Cd, U, Ba, Bi, Cs, Rb, Tl, Sr, Al, V, Fe, Cu, Mn, Zn, Co, Ag were determined by inductively coupled sector field mass spectroscopy (ICP-SFMS) after sample digestion by a combination of HF, HNO3, and H2O2 in ultraclean conditions. Quality control of the analytical procedure was carried out by blank control, by evaluating the limits of detection, recoveries and repeatability. Concentrations found are extremely low for most metals, confirming the high purity of Antarctic aerosol. Principal Component Analysis (PCA) highlights high correlations among Pb, Cr, Bi, Cu and Zn concentration values and among Li, U, Ba, Cs, Rb, Al, V, Fe, Mn, Co concentration values permitting the identification of two principal source groups, namely crustal dust and human emission activities. Elements of anthropogenic origins (Pb, Cr, Cu, Zn) were highly enriched with respect to their crustal composition.

Characterization of carbons from olive cake by sorption of wastewater pollutants.

Studies has been conducted to compare the sorption properties between raw carbons made from olive cake and commercial activated carbons to remove aquatic pollutant such as heavy metal (HM), phenol (Ph), dodecylbenzenesulfonic acid-sodium salt detergent (DBSNa) and methylene blue dye (MB). Effect of acidic treatments by H2SO4, HCl and HNO3 on the sorption properties of olive cake carbon (OCC) were studied by mass titration, SEM photographs, sorption isotherms. It is found that acidic treatment changes the surface properties of OCC but do not enhance its sorption capacity. Compared to commercial activated carbons the OCC derivatives generally are equally able to uptake HM and Ph from solution but MB and DBSNa are not. This different behaviour is to attribute to manufacturing and activation treatments so as surface groups of the precursor sorbent material. For the heavy metals, chromium and silver were removed effectively but to small extent cadmium. This may be because of the various charge densities of metal elements tested. The results of the multiple experiments indicate that sorption of cadmium ions can be significantly improved by the presence of complexing agents sorbed from the carbon. An empirical mathematical form is proposed to correlate experimental data and to compare the performance of the different sorbent materials.

Tumour proliferation, angiogenesis, and ploidy status in human colon cancer.

AIMS: Tumour angiogenesis is essential for carcinogenesis and facilitates the process of tumour development and metastasis. Vascular endothelial growth factor (VEGF) is a well characterised angiogenetic factor and is known to play a crucial role in new vessel development. To gain further insight into the effects of microvessel density and VEGF expression in colon cancer, their relation with tumour proliferation, ploidy status, and p53 expression was investigated in colon cancer. METHODS: Tissue samples of 50 archived colon cancers were analysed by immunohistochemistry for VEGF, p53, and the endothelial cell marker, von Willebrand factor (VWF), using specific antibodies. The same samples were re-cut for flow cytometric studies to obtain S phase fraction (SPF) and ploidy status. RESULTS: A positive significant correlation was found between SPF and angiogenesis. The median microvessel count in high SPF tumours was significantly higher than in low SPF ones. No association was found between VEGF expression and SPF. A positive correlation was found between ploidy status and p53 expression and microvessel count. Furthermore, a positive correlation was established between DNA ploidy, VEGF expression, and microvessel count. CONCLUSION: This study provides evidence that in colon cancer, tumour growth may be stimulated by vascular supply, and the lack of a correlation between tumour cell proliferation and VEGF expression indicates that these two parameters may be regulated by separate mechanisms. Furthermore, the positive correlation between microvessel density, VEGF expression, and ploidy status provides more evidence that genetic alterations are involved in tumour angiogenesis.

Ischemic stroke and fibrinogen in the elderly.

Senescence is accompanied by an important increase in prevalence and incidence of ischemic stroke. The plasma level of fibrinogen tends to increase with age in the elderly similarly to the prevalence of stroke. The aim of our study was to evaluate the age-related increase in fibrinogen plasma level in the elderly and to assess the presence of eventual differences between normal subjects and patients with previous ischemic stroke associated with precerebral atherosclerosis. Eighty inpatients (41 males and 39 females), consecutively admitted to our Geriatric Unit, were included to this study. The patient group was formed 32 subjects (20 males and 12 females) aged 50-79 years, suffering from cerebrovascular disease with one or several previous ischemic stroke episodes, having occurred at least 1 year earlier. The control group consisted of 48 normal subjects (21 males and 27 females) aged 50-79 years. Both control and patient groups were subdivided into three subgroups, according to their age: Group 1 (50-59 years), Group 2 (60-69 years)and Group 3 (70-79 years). The statistical comparison was carried out by means of the Mann-Whithney nonparametric test. In normal controls, a mild age effect is evident because only Group 3 shows fibrinogen levels significantly higher than those of Group 1. On the contrary, in patients with ischemic stroke, an age effect is already evident between Group 2 and Group 1; of course, also the comparison between patient Group 3 and Group I shows a statistically significant difference. Moreover, the levels of fibrinogen were significantly increased in patient Group 2 and 3 when compared to those of their respective age-matched controls. Our data are in agreement with those already available in the literature and demonstrate that fibrinogen in normal aging changes with age and shows a 19 %increase between age Group 1 and Group 3. Patients with ischemic stroke show an earlier and more evident age-related increase in fibrinogen than normal controls. Even if it is not possible to know, if the increase in fibrinogen is a consequence or not of the ischemic stroke, we can affirm that certainly the increased levels of fibrinogen should be considered as an important risk factor in the elderly for cerebrovascular disease and deserve treatment.

Isolated monolateral neurosensory hearing loss as a rare sign of neuroborreliosis.

Lyme disease, or borreliosis, is a zoonosis transmitted by Borrelia burgdorferi which also involves the central nervous system (CNS), in 15% of affected individuals, with the occurrence of aseptic meningitis, fluctuating meningoencephalitis, or neuropathy of cranial and peripheral nerves. Encephalopathy with white matter lesions revealed by magnetic resonance imaging (MRI) scans in late, persistent stages of Lyme disease has been described. In this report, we describe a patient with few clinical manifestations involving exclusively the eighth cranial nerve, monolaterally and diffuse bilateral alterations of the white matter, particularly in the subcortical periventricular regions at cerebral MRI. This single patient study shows that the search for antibodies against Borrelia burgdoferi should always be performed when we face a leukoencephalopathy of unknown origin. An isolated lesion of the eighth cranial nerve can be the only neurologic sign in patients with leukoencephalopathy complicating Lyme disease.