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.

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.

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.

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)).

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.

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.

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

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.

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.

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.

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.

Plasma fibronectin in normolipidaemic and hyperlipidaemic uraemic patients treated with haemodialysis.

Plasma fibronectin (PF) concentrations, were investigated in normolipidaemic and hyperlipidaemic (type IV) patients with chronic renal failure treated with hemodialysis (n = 29) and in controls (n = 34). Mean PF was significantly reduced in both subsets of dialysed patients. Among the hemodialysed patients the presence of hyperlipidaemia did not modify PF levels, which resulted, on the contrary, significantly higher in hyperlipidaemic controls as compared with the normolipidaemic group. In controls, according to a multivariate analysis model, PF was directly related with age and inversely with HDL-cholesterol. In the hemodialysed patients total cholesterol was the unique significant PF related variate, being this group, therefore, characterized by the lack of any inverse relation between PF and HDL-cholesterol. Finally, no PF modifications were observed in hemodialyzed patients affected by arterial hypertension or clinically evident atherosclerotic lesions.

Isolated rectal relapse in non Hodgkin lymphoma patient.

The authors report on case of isolated rectal relapse of non Hodgkin lymphoma after complete remission with chemotherapy. They analyse diagnostic and therapeutic aspects, on the grounds of literature data and personal experience.

Defibrotide in the prevention of venous irritation by vinorelbine administration.

BACKGROUND: Vinorelbine is active in a variety of malignancies. The most common side effects are leukopenia and granulocytopenia, moreover Vinorelbine is a vescicant and venous irritant, the incidence of the latter being 10-26% in patients who received VNB as a 20-30 minute peripheral infusion. To prevent venous toxicity we have carried out a study in order to evaluate the efficacy of Defibrotide in this issue. MATERIALS AND METHODS: 41 patients were enrolled in the study, the experimental schedule was: Defibrotide 400 mg on 250 cc of normal saline iv, after 15 minutes of infusion, we delivered quick, brief and repeated pulses of Vinorelbine through the plastic tube followed by remaining Defibrotide: For grading venous irritation we used the scale by Rittenberg et al. RESULTS: A total of 360 infusion were delivered, the incidence of any venous irritation was 5% and maximum grade 2. No severe toxicity was recorded. CONCLUSION: These data show that Defibrotide might serve as a therapeutic drug to prevent vascular toxicity by Vinorelbine.

Somatosensory evoked potentials in patients affected by unilateral cerebrovascular lesions with onset during the perinatal period or adulthood.

Unilateral cerebrovascular lesions occurring during adulthood have been reported to be accompanied by high-amplitude somatosensory evoked potentials over the nonaffected hemisphere; however, the mechanisms by which somatosensory evoked potential amplitude increases over the nonaffected hemisphere are still unclear. To investigate the eventual presence of similar amplitude abnormalities in children, we recorded somatosensory evoked potentials in three groups of patients: one with unilateral cerebrovascular lesions that occurred during the perinatal period and another two with unilateral cerebrovascular lesions occurring during late adulthood or old age. Group 1 was comprised of 12 children and young adults (age range 2 3/12-31 years, 6 males and 6 females) who suffered from unilateral cerebrovascular lesion with perinatal onset. Four control groups were arranged with age matched to that of the patients. Adult patients were subdivided into two subgroups (group 2: n = 10, all males; group 3: n = 18, 12 males and 6 females) on the basis of the presence or absence of sensory impairment over the hemiplegic side. In group 1, the four youngest subjects, aged less than 6 years, were found to show somatosensory evoked potentials of abnormally high amplitude over the nonaffected hemisphere, with a "giant" main negative wave at around 45 ms (range 38.7-49.2), strictly localized over the central areas contralateral to the lesion; in normal controls, there was no such wave. All patients in group 2 were found to be affected by large infarctions in the territory of the middle cerebral artery, whereas patients in group 3 presented with subcortical lesions of the internal capsule isolated or in association with an involvement of the frontal and/or temporal cortex. Regarding somatosensory evoked potential parameters measured over the nonaffected hemisphere in adult/elderly subjects, a significant difference was observed for N20 and P22 latency, which was longer in both groups of patients than in controls. There is a significant difference in the neurophysiologic consequences of unilateral cerebrovascular lesion, as well as over the nonaffected hemisphere, if it occurs during early infancy or during adulthood. Our findings show a new type of "giant" somatosensory evoked potentials in some children affected by unilateral cerebrovascular lesion with perinatal onset.

Reoperations for acute prosthetic thrombosis and pannus: an assessment of rates, relationship and risk.

OBJECTIVE: Mechanical valvular prostheses have the advantage of longevity but carry a risk of thrombosis which is dependant on valve design, materials and host-related interface. While pannus is common to both biologic and mechanical valves, acute prosthetic thrombosis is mostly a complication of mechanical valves; therefore we investigated to find rates and risk of these obstructive complications. METHODS: Between 1/1/70 and 31/12/97, 2680 patients received at least one mechanical prosthesis in the aortic or mitral or tricuspid position and a total of 3014 operations were performed. Follow-up included 18523 years and was 98% complete. Incidence rates, Kaplan-Meier estimates, modeling of the hazard and multivariate analysis in the hazard domain were used in the analysis. RESULTS: Overall survival was 76%, 64%, 51%, 38.5% and 29% at 5, 10, 15, 20 and 25 years, respectively. It was significantly better in aortic than in mitral than in double prosthesis. 290 patients received a single reoperation, 37 a second, six a third and one a fourth reoperation. Two-hundred and fifty-one of these reoperations were exclusively due to malfunction of mechanical prosthesis, nine to malfunction of both mechanic and biologic prostheses. Most frequent reoperative indications was dehiscence (133), pannus (48) and thrombosis (29). The linearized rate of reoperations for pannus was 0.24%/patient per year, for valvular thrombosis 0.15%/patient per year. The shape of the thrombotic hazard was constant (at random) and the relative risk 12 times higher for tricuspid prosthesis, seven times higher for mitral prosthesis. Multivariate analysis controlling for prosthetic position, age, sex and prosthetic size, showed a 67% risk reduction with larger prosthesis (>27 mm), a 69% risk reduction with the Sorin tilting disk prosthesis and an 83% risk reduction with the bileaflet prosthesis. Pannus hazard shows a delayed exponential rise and was two times higher in tricuspid and three times higher in mitral position. Multivariate analysis showed a 50% risk reduction with larger prosthesis, an 11 times higher hazard of old (caged-disk, caged ball) prosthesis and a three times higher hazard of Lillehei-Kaster prosthesis. Reoperation for thrombosis has a 62% perioperative (30 days) survival compared to 92% survival of pannus reoperation. CONCLUSIONS: Mechanical valves have a low incidence of reoperation, mostly for prosthetic dehiscence. Pannus development is the next frequent complication increasing with time since implant, therefore in this series it was related to old valvular models and tilting disk prosthesis, with longer follow-up. Acute thrombosis occurs significantly earlier than pannus formation. Despite shorter follow-up we are therefore confident that bileaflet prostheses are less prone to this complication and pannus is a rare early etiologic factor. Thrombosis has very high operative risk as compared to pannus, justifying the present trend to thrombolysate selected cases.