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Funding Acknowledgements Type of funding sources: None. Background In case of persistent atrial fibrillation (AF), atrial substrate assumes a dominant role in sustaining the arrhythmia. Recent studies prove that low voltage areas (LVA, Voltage Amplitude < 0,5 mV) represent an additional target for ablation of AF patients. Purpose The purpose of this study is to analyse whether structural atrial conduction abnormalities (i.e., pivot sites and slow conduction corridors) may occur outside low voltage areas. Methods The study is based on the retrospective analysis of 31 consecutive maps of patients undergoing AF ablation (16 paroxysmal and 15 persistent cases). The clinical procedures have been performed with the support of a mapping system. Sinus rhythm activation maps and bipolar maps used for this analysis have been created with a multipolar mapping catheter. Map points were only acquired when the electrode was in contact with the endocardial tissue to avoid misleading voltage amplitude information. Slow conduction corridors and pivot sites have been analysed. At these sites, EGMs characterization included voltage amplitude (mV), signal duration (ms) and fractionation. Results The average value of EGMs amplitude reported at pivot sites and slow conduction zones, respectively, amounted to 2,08 ± 0,63 mV and 2,1 ± 0,66 mV in paroxysmal cases. In persistent cases, there were slight decreased values to 1,95 ± 0,93 mV and 1,89 ± 0,89 mV. Characterization at pivot sites documented a mean duration value of 45,4 ± 4,64 ms and 49,93 ± 5,51 ms in paroxysmal and persistent patients, respectively, while in slow conduction zones 41,53 ± 7,94 ms and 49,04 ± 6,41 ms have been reported. As for fractionation, more than five deflections per signal have been identified in all abnormal conduction areas. Conclusion Our study proves that functional electrophysiological phenomena can occur outside low voltage areas, even in persistent cases. According to this analysis, not all LVA represent the correct target for catheter ablation, encouraging the development of further methods for investigation of atrial substrate.

Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) progresses with a cascade of combined structural, functional, and systemic dysfunctions. Electro-anatomical maps are employed to investigate pro-arrhythmic areas, characterized by abnormal electrical properties. However, single rhythm maps provide only a partial reconstruction: rhythm and wavefront directionality might mask some of these areas. Purpose To demonstrate that the combined quantitative analysis of different rhythm maps (i.e., parallel sinus rhythm and paced maps) could allow consistent identification of structural and functional defects sustaining AF. Methods Thirty AF clinical procedures have been performed with mapping system support. In particular, a sinus rhythm activation map and a paced map have been created with a multipolar catheter exploiting the parallel mapping feature by setting an extra beat (pacing interval = ERP + 40 ms) every three sinus beats. Areas of abnormal conduction have been identified and a comparison of electrophysiological biomarkers (EGMs voltage and fractionation) among the two rhythms has been performed. Results This comparative analysis allowed us to identify both structural and functional electrophysiological phenomena. Specifically, we distinguished: (i) abnormal conduction zones confirmed in both maps, both characterized by signal fractionation and a lower voltage (0,56 ± 0,18 mV) with respect to healthy atrial tissue (2,40 ± 0,41 mV), and (ii) abnormal conduction zones visible in only one of the two maps. In the latter, we distinguished whether the absence of the phenomena was due to wavefront orthogonality to the diseased area (revealed in paced rhythm thanks to a change in wavefront direction) or due to the presence of a functional phenomenon induced by the pacing. In the first group signal fractionation has been detected in both rhythms and a lower voltage has been found (1,79 ± 1,1 mV) with respect to normal conduction zones (3,26 ± 0,98 mV), while in functional cases EGMs fractionation has been identified only in paced maps and no significant difference has been observed in terms of voltage. Conclusion Double rhythm mapping provides a more robust characterization of atrial abnormal conduction phenomena. In fact, it allowed the distinction of true structural dysfunctions from dynamic (functional) ones thanks to the different wavefront directionality and rhythm. Moreover, the structural defects have been confirmed by EGMs analysis, which revealed both low voltage amplitude and high fractionation, characteristics that have not been reported in functional cases.

Funding Acknowledgements Type of funding sources: None. Background The ongoing challenge is to generate meaningful data during electrophysiological (EP) studies, integrating the knowledge on atrial fibrillation (AF) progression gained by the EP community in the latest years. At the present time there is a lack of EP protocols: most of the centers perform electroanatomical (EA) ablation to isolate pulmonary veins or, in persistent AF forms, some centers propose the performance of additional lines for atrial compartmentalization. However, none of these approaches take in consideration neither the wavefront propagation nor the analysis of functional phenomena. Purpose To investigate whether zones of delayed conduction (slow conduction, SC) or functional propagation (pivot sites, PS) may play a role in terms of maintenance of paroxysmal (PAF) and persistent (PsAF) AF. Methods Twenty-seven consecutive patients with PAF (14 patients) and PsAF (13 patients) have been enrolled in this study. For each patient, a sinus rhythm activation map and a paced map have been created with a multipolar catheter exploiting the parallel mapping feature. According to these activation maps, we analyzed the wavefront propagation. Abnormal conduction was defined as a delimited zone in which the propagation became suddenly slower (90°, pivot sites). At each of these sites, EGMs were collected and analysed in terms of amplitude (mV), location and fractionation. Results In sinus rhythm maps, a total number of 65 pivot sites and slow conduction corridors was identified. In the PAF group 22 PS and SC were found (1,6/pt), whereas those included in the PsAF one showed a significantly higher number: 43 (3,3/pt). The bipolar voltage value reported at abnormal conduction areas amounted to 1,95 ± 0,93 mV and 1,78 ± 0,54 mV for PAF and PsAF patients, respectively, showing a lower value with respect to healthy tissue areas (2,94 ± 4,81 mV). More than four deflections per signal were identified in 57/65 PS and SC zones. In PsAF cases, these areas were mainly found on the posterior wall. A concordance with esophagus location occurred in the 89%. In paced maps, instead, we documented an average value of 38 PS and SC zones (1,5/pt), of which 27 in persistent patients. As for bipolar values, a lower voltage value was reported in PS and SC zones (1,91 ± 0,69 mV for PAF and 1,52 ± 0,36 mV for PsAF) with respect to normal conductive tissue. Fractionation of EGMs was confirmed in almost all cases. Conclusion The main findings of this analysis are: (i) in PsAF patients the number of pivot sites is higher with respect to PAF cases; (ii) In PsAF patients, abnormal conduction phenomena are predominantly localized on the posterior wall, with a strong correlation with esophagus location; (iii) slow conduction zones and pivot sites are characterized by lower voltage amplitude and higher fractionation with respect to normal conduction areas.

Background: Colon delivery systems are designed for the oral delivery of active compounds in the large intestine. Food-grade copolymers Eudraguard® Biotic (EUGB) and control (EUGC) have been investigated to develop colloidal systems loading natural active ingredients. Methods: In this study, we evaluated the degradation process of these matrices in simulated gastric, intestinal and colonic conditions. Microparticles made of EUGB and EUGC, alone or in combination, were loaded with the model compound resveratrol (RSV). A parallel study was performed on in vitro RSV release and SEM analysis of microparticles kept at different pH values. Results: All systems ensured a limited gastric release of RSV (below 20%), presenting only small pores on the surface of microparticles treated with simulated gastric fluid. EUGB microparticles showed the maximum release in simulated colon fluid (SCF), showing a complete dissolution of the microparticle matrix. The EUGC-based system allowed a prolonged release of RSV over time, and in SCF, it showed only partial degradation. Using mixed EUGB/EUGC matrices, a prolonged RSV release was observed along the intestinal tract. Conclusion: Overall, EUGB and EUGC copolymers were able to modulate and localize the release of entrapped cargo in the small intestine and colon. They could have interesting applications in treating bowel diseases synergistically with other therapeutic strategies.

Background Recently the distal radial access (DRA) technique has been introduced for coronary angiography and intervention as an alternative to the conventional radial access (RA). Purpose The aim of this study was to provide a quantitative appraisal of the effects of DRA vs conventional RA for coronary angiography with or without intervention. Methods The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for randomised clinical trials (RCT) comparing DRA versus RA for coronary angiography and/or intervention. Data were pooled by meta-analysis using a random-effects model. The number of patients needed to treat for an additional beneficial outcome (NNTB) and the number needed to treat for an additional harmful outcome (NNTH) were calculated. The primary endpoint was radial artery occlusion (RAO) at the longest available follow-up. Additional secondary outcomes were assessed. Results A total of 13 RCT including 4,901 patients were identified and included in the final analysis. Coronary angiography alone was performed in 3 studies, percutaneous coronary intervention was performed in a variable proportion of patients ranging from 24% to 100% across studies. Study population included patients with chronic coronary syndrome in the large majority, and the proportion of acute coronary syndrome ranged from to 31% to 100% across studies. Compared with RA, DRA was associated with a significant lower risk of RAO, either detected at the longest follow-up (risk ratio [RR]: 0.36; 95% CI: 0.23 to 0.58; p Conclusions Compared with RA, DRA is associated with lower risks of RAO and EASY ≥ II hematoma, but requires longer time for radial artery puncture and sheath insertion, more puncture attempts and a higher access site crossover. Funding Acknowledgement Type of funding sources: None.

Background Systemic sclerosis (SSc) myocarditis is common, but often underrecognized due to absence of symptoms at early stages. Cardiac Magnetic Resonance (CMR) is the imaging modality of choice for detection of SSc myocarditis. Current guidelines recommend CMR in case of alterations in first level cardiologic diagnostic tests. Immunosuppressive therapy is only indicated for patients with organ involvement, i.e. most frequently heart and lung, or with diffuse cutaneous systemic sclerosis. Purpose To explore the impact of CMR in the diagnostic and therapeutic pathway of SSc patients. Methods Of 286 SSc patients referred to our hospital, we retrospectively enrolled patients who received CMR during an observational period of 6 years (2016–2022). Exclusion criteria were previous immunosuppressive therapy and cardiopathy from other cause. Clinical data including Holter-ECG performed within 90 days from CMR were available. Results 39 patients (67 [58–72] years; females 87%) were identified. 15 patients were excluded due to previous immunosuppressive therapy (9), lack of information on therapy (3), cardiopathy from other causes (3). 24 patients were finally included in the study. 14 patients (58%) did not show myocardial inflammation at CMR (LVEF 65.5 [61–69]%, LVEDV 114.5 [92–141] ml, T2 ratio 1.6 [1.4–1.9]). 1 patient presented with mid-wall inferior late gadolinium enhancement (LGE) indicative of previous myocarditis. 1 patient received immunosuppressive therapy due to SSc lung involvement in follow-up. In this group premature ventricular contractions (PVCs) during 24-hours Holter-ECG were rare (29 [3–48]). When measured, high-sensitivity Troponin I (hsTnI) was 2.4 [0.8–5] ng/L. 10 patients (42%) showed myocardial inflammation at CMR: LVEF 60 [56–65] %, LVEDV 137,5 [122–166] ml, T2 ratio 2.1 [1.7–2.3], T1 mapping 1022.5 [1010–1036] msec and T2 mapping 50.5 [50–52] msec. Myocardial LGE with non-ischemic pattern was seen in 6 patients. The number of PVCs at 24-hours Holter-ECG was collectively higher in these patients (354 [1–4245]). When measured, hsTnI was 8 [6–18] ng/L. With detection of myocardial inflammation at CMR all 10 patients eventually received immunosuppressive therapy (mycophenolate mofetil (MMF) or azathioprine in case of MMF intolerance). At follow-up CMR performed 4 [3–6] months later on therapy various parameter differences were observed: LVEF (+2 [−2; 4] %), T1 mapping (−23 [−27; −12] msec), T2 mapping (−2 [−4; −1] msec), T2 ratio (−0.5 [−0.6; −0,2]). Of 6 patients with LGE, 4 displayed LGE persistence at follow-up. Conclusions In our experience, CMR was the tool of choice for diagnosis and therapeutic management in SSc patients with suspected cardiac involvement. SSc myocarditis patients tended to display more arrhythmic burden at Holter-ECG and higher cardiac biomarkers. Our data suggest to intensify first level cardiological screening, in order to identify suitable candidates to CMR. Funding Acknowledgement Type of funding sources: None.

Introduction STEMI is one of the cardiac emergencies whose management has been mostly challenged by the COVID-19 pandemic. Patients presenting with the “lethal combo” of STEMI and concomitant SARS-CoV-2 infection have faced dramatic issues related to need for self-isolation, systemic inflammation with multi-organ disease, and difficulties to obtain timely diagnosis and treatment. Methods We performed a systematic search of three electronic databases from February 1st 2020 to January 31st 2022. We included all studies reporting crude rates of in-hospital outcomes of STEMI patients with concomitant COVID-19. Results A total of 9 observational studies were identified, mainly conducted during the first wave of the pandemic. STEMI patients with COVID −19 were more likely Afro-American and displayed higher rates of hypertension and diabetes with lower smoking prevalence. Associated comorbidities, including coronary artery disease, prior stroke and chronic kidney disease were also more common in those with SARS-CoV-2 infection. At coronary angiography, a higher thrombus burden in COVID-19 positive STEMI patients was highlighted, with up to 10-fold higher rates of stent thrombosis and greater need for glycoprotein IIb/IIa inhibitors and aspiration thrombectomy; this was not always associated with prolonged times from symptom onset to hospital admission and door-to-balloon. COVID-19 positive STEMI patients were less likely to receive coronary angiography and primary PCI, and more likely to be treated with fibrinolytics only. At the same time, patients with Covid-19 were more prone to present MINOCA. In-hospital mortality ranged from 15% to 40%, with consistent variability across different studies and subjects who tested positive for SARS-CoV-2 did also present higher rates of cardiogenic shock, cardiac arrest, prolonged ICU stay, mechanical ventilation, major bleeding, and stroke. Conclusion The coexistence of STEMI and COVID-19 was associated with increased in-hospital mortality and poor short-term prognosis. This was not entirely attributable to logistic issues determining delayed coronary revascularization, since patients' specific clinical and angiographic characteristics, including higher burden of cardiovascular risk factors and greater coronary thrombogenicity might have substantially contributed to this trend. Funding Acknowledgement Type of funding sources: None.

Background In case of persistent atrial fibrillation (AF), atrial substrate assumes a dominant role in sustaining the arrhythmia. Recent studies prove that low voltage areas (LVA, Voltage Amplitude < 0,5 mV) represent an additional target for ablation of AF patients. Purpose. The purpose of this study is to analyse whether structural atrial conduction abnormalities (i.e., pivot sites and slow conduction corridors) may occur outside low voltage areas. Methods The study is based on the retrospective analysis of 31 consecutive maps of patients undergoing AF ablation (16 paroxysmal and 15 persistent cases). The clinical procedures have been performed with the support of a mapping system. Sinus rhythm activation maps and bipolar maps used for this analysis have been created with a multipolar mapping catheter. Map points were only acquired when the electrode was in contact with the endocardial tissue to avoid misleading voltage amplitude information. Slow conduction corridors and pivot sites have been analysed. At these sites, EGMs characterization included voltage amplitude (mV), signal duration (ms) and fractionation. Results The average value of EGMs amplitude reported at pivot sites and slow conduction zones, respectively, amounted to 2,08 ± 0,63 mV and 2,1 ± 0,66 mV in paroxysmal cases. In persistent cases, there were slight decreased values to 1,95 ± 0,93 mV and 1,89 ± 0,89 mV. Characterization at pivot sites documented a mean duration value of 45,4 ± 4,64 ms and 49,93 ± 5,51 ms in paroxysmal and persistent patients, respectively, while in slow conduction zones 41,53 ± 7,94 ms and 49,04 ± 6,41 ms have been reported. As for fractionation, more than five deflections per signal have been identified in all abnormal conduction areas. Conclusion Our study proves that functional electrophysiological phenomena can occur outside low voltage areas, even in persistent cases. According to this analysis, not all LVA represent the correct target for catheter ablation, encouraging the development of further methods for investigation of atrial substrate.

Introduction Shark fin sign, also known as triangular QRS–ST–T waveform (TW), is characterized by a giant R wave (amplitude ≥ 1 mV) resulting from the fusion of the QRS complex, the ST–segment and the T wave and showing triangular morphology. TW pattern is quite uncommon and reveals a life–threatening condition that needs aggressive management. Case presentation: A 45–year–old black man with history of arterial hypertension and without known comorbidities arrived at our emergency department (ED) with out–of–hospital cardiac arrest (OHCA). Return of spontaneous circulation occurred after 11 minutes and 2 direct current shocks. At arrival in the ED, he was hemodynamically stable, electrocardiogram showed atrial fibrillation without repolarization abnormalities, and echocardiogram revealed left ventricular hypertrophy and hypokinesia of the mid–basal inferior wall. Plasma level of electrolytes and high–sensitivity troponin were in range. Sedation in the ED was needed due to psychomotor agitation. He was transferred to the cardiac intensive care unit; no arrhythmias were noted. During the night, electrocardiogram monitoring revealed a progressive ST segment elevation in inferior leads up to a triangular QRS–ST–T giant waveform (“Shark fin sign”), confirmed at 12–lead electrocardiogram. After 3 minutes the electrocardiogram showed a progressive and complete resolution of ST–elevation. Akinesia of the inferior wall was confirmed at echocardiogram. The episode repeated 5 more times in the following 40 minutes, while waiting for the arrival of the Cath lab personnel. Coronary angiography revealed a sub–occlusive mid right coronary artery (RCA) stenosis. Percutaneous coronary intervention with the implantation of one drug eluting stent was performed. After the procedure the patient was hemodynamically stable, and the ECG did not show any other abnormality and no episodes of recurrent ST–elevation occurred. Conclusion The shark fin sign refers to the abrupt total deprivation of blood flow in large areas of myocardium that are seen during coronary thrombotic occlusion or vasospasm. In our case we assisted to transient but repetitive inferior triangular ST–elevation, probably the expression of RCA plaque coronary vasospasm that cause the ECG shark fin sign and OHCA. This sign correlates with high risk of cardiogenic shock, electrical instability, and cardiac arrest, thus requiring prompt and aggressive management.

Background Pulmonary veins isolation (PVI) represents the main strategy for paroxysmal atrial fibrillation (AF) treatment. Due to the poor clinical outcomes of PVI in case of non–paroxysmal AF, significant efforts have been made to develop new ablative strategies to modify the atrial substrate. Up to now, in order to characterise atrial substrate, only bipolar voltage maps have been used and impedance mapping has never been evaluated. Purpose Our aim is to demonstrate the potential correspondence among atrial wall thickness, bipolar voltage and impedance. Atrial impedance mapping could represent an additional tool for atrial substrate characterization, providing further information on tissue conductive properties and confirming bipolar substrate analysis. Methods The study includes the retrospective analysis of 60 electro–anatomical (EA) maps of patients with paroxysmal (40 patients) and persistent (20 patients) AF admitted to our institution for treatment. The clinical procedures have been performed with the support of CARTO3 mapping system. Map points have been collected with Navistar RMT Thermocool ablation catheter in order to enable the evaluation of atrial impedance values. To perform the correspondence analysis between the voltage map and impedance map, the atrial endocardial surface has been divided in six sections. Before ablation, for all patients a computed tomography has been performed in order to evaluate atrial endocardial thickness. Parameters of interest that have been evaluated in this study are EGMs voltage amplitude (mV) and fractionation (> five deflections per signal) and the corresponding impedance value (Ohm) at the considered acquisition point. Results In all PAF cases no voltages lower than 0.5 mV have been reported. The corresponding impedance values ranged from 140.6 to 169.9 Ohm, with an average value of 151.5 ± 5.4 Ohm. In PsAF cases, instead, voltage values inferior to 0.05 mV have been reported in the posterior wall, anterior wall and roof in 19/20 patients. In these low voltage areas, long duration fractionated signals have been reported and the average impedance value dropped to 129.1 ± 3.8 Ohm, ranging from 110.2 Ohm to 139.6 Ohm. Conclusion Our study supports the association between left atrial thickness, voltage amplitude and impedance values. This allows the correct substrate evaluation in case of uncertain bipolar values thanks to additional information provided by impedance mapping.

Background Atrial fibrillation (AF) progresses with a cascade of combined structural, functional, and systemic dysfunctions. Electro–anatomical maps are employed to investigate pro–arrhythmic areas. However, single rhythm maps provide only a partial reconstruction: rhythm and wavefront directionality might mask some of these areas. Purpose. To demonstrate that the combined quantitative analysis of different rhythm maps (i.e., parallel sinus rhythm and paced maps) could allow consistent identification of structural and functional defects sustaining AF. Methods Thirty AF clinical procedures have been performed with mapping system support. In particular, a sinus rhythm activation map and a paced map have been created with a multipolar catheter by setting an extra beat every three sinus beats. Areas of abnormal conduction have been identified and a comparison of electrophysiological biomarkers (EGMs voltage and fractionation) among the two rhythms has been performed. Results This comparative analysis allowed us to identify both structural and functional electrophysiological phenomena. Specifically, we distinguished: (i) abnormal conduction zones confirmed in both maps, both characterized by signal fractionation and a lower voltage (0,56 ± 0,18 mV) with respect to healthy atrial tissue (2,40 ± 0,41 mV), and (ii) abnormal conduction zones visible in only one of the two maps. In the latter, we distinguished whether the absence of the phenomena was due to wavefront orthogonality to the diseased area (revealed thanks to a change in wavefront direction) or due to the presence of a functional phenomenon induced by the pacing. In the first group signal fractionation has been detected in both rhythms and a lower voltage has been found (1,79 ± 1,1 mV) with respect to normal conduction zones (3,26 ± 0,98 mV), while in functional cases EGMs fractionation has been identified only in paced maps and no significant difference has been observed in terms of voltage. Conclusion Double rhythm mapping provides a more robust characterization of atrial abnormal conduction phenomena which better represent AF electrical substrate. It allows the distinction of true structural dysfunctions from dynamic ones thanks to the different wavefront directionality and paced rhythm. Moreover, the structural defects have been confirmed by EGMs analysis, which revealed both low voltage amplitude and high fractionation, characteristics that have not been reported in functional cases.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): German Center for Cardiovascular Research (DZHK) Background/Introduction RPs are young, hyper-reactive and RNA-rich platelets. They have a pro-thrombotic potential, are predictors of an insufficient response to antiplatelet therapy after myocardial infarction and are suggested to play a key role in patients with chronic coronary syndrome (CCS) and high on-treatment platelet reactivity. Moreover, RPs are promising novel biomarkers for the prediction of adverse cardiovascular events in different pathological settings. Purpose We aimed to compare for the first time the transcriptomic profiles of RPs and MPs in CCS patients. Method Using fluorescent activated cell sorting (FACS), we isolated RPs and MPs based on their RNA content from peripheral blood of 19 CCS patients. After sorting, RNA was extracted and quality, concentration and integrity were assessed with the Tapestation 4200 platform (Agilent). TotalRNA libraries were prepared, multiplexed and sequenced on a NextSeq 500 Illumina platform obtaining 80 to 100 million paired-end reads per sample. RNA-sequencing analysis was performed with R and DESeq2, a cut-off of p 1 was applied. Alternative splicing event detection and analysis was performed with MAJIQ. We performed circular RNA (circRNA) analysis using CIRCexplorer. Results With total RNA-sequencing, we detected 1589 genes differentially expressed with 1100 transcripts upregulated in RPs, while 489 were enriched in MPs (Figure 1 A and B). In particular, transcripts for the collagen receptor GP6 (log2FC 1.12, p=6.89x10-41), thrombin receptor PAR4 (F2RL3, log2FC 1.1, p=3.54*10-21) and Von Willebrand Factor (log2FC 1.2, p value 1.26*10-38) were significantly enriched in RPs. We found an enrichment in MPs of transcript coding for genes involved in RNA processing such as the splicing regulator LUC7L3 (log2FC -1.01, p value 6.65*10-22). We detected several splicing events differentially regulated: an alternative splicing on the transcript GP6 is upregulated in RPs (Figure 1C); by the G-protein GNAQ transcript, one alternative splicing event was found upregulated in RPs, while two others were upregulated in MPs. Additionally, we detected an enrichment of the total level of circular RNAs in MPs compared to RPs (Figure 1E). Nevertheless, several circular RNAs that have not been described before were found enriched in RPs (Figure 1F). Conclusion This study represents the first transcriptomic profiling of RPs and MPs in patients with CCS and provides for the first time a biological explanation of RPs’ hyper-reactivity. The clear upregulation of prothrombotic signaling in RPs could provide and explanation to their hyperactivity and their correlation with cardiovascular events in different pathological settings. Altogether, these findings shed light on a new therapeutic niche in CCS patients. Nonetheless, the detrimental role of RPs in patients with coronary artery disease requires further investigations

Background Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma (AHLM/LMM) may be very difficult to diagnose at an early stage. Objectives To quantify the predictive value of dermoscopic and reflectance confocal microscopy (RCM) features for AHLM/LMM. Methods Dermoscopic and RCM images of histopathologically diagnosed AHLM/LMM, amelanotic/hypomelanotic benign lesions (AHBL), and amelanotic/hypomelanotic basal and squamous cell carcinomas (AHBCC/AHSCC) of the head and neck from consecutive patients were retrospectively collected and blindly evaluated by three observers to assess presence or absence of dermoscopic and RCM criteria. Results Overall, 224 lesions in 216 patients including LM/LMM (n = 55, 24.6%), AHBL (n = 107, 47.8%) and AHBCC/AHSCC (n = 62, 27.7%) were analysed. Multivariable analysis showed that milky-red areas (OR = 5.46; 95% CI: 1.51-19.75), peripheral light brown structureless areas (OR = 19.10; 4.45-81.96), linear irregular vessels (OR = 5.44; 1.45-20.40), and asymmetric pigmented follicles (OR = 14.45; 2.77-75.44) at dermoscopy, and >= 3 atypical cells in five fields (OR = 10.12; 3.00-34.12) and focal follicular localization of atypical cells at dermo-epidermal junction (DEJ) (OR = 10.48; 1.10-99.81) at RCM were significantly independent diagnostic factors for AHLM/LMM vs. AHBL. In comparison with AHBCC/AHSCC, peripheral light brown structureless area (OR = 7.11; 1.53-32.96), pseudonetwork around hair follicles (OR = 16.69; 2.73-102.07), and annular granular structures (OR = 42.36; 3.51-511.16) at dermoscopy and large dendritic (OR = 6.86; 3.15-38.28) and round pagetoid cells (OR = 26.78; 3.15-227.98) at RCM led to a significantly increased risk of diagnosing AHLM/LMM. Conclusions Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma may have the same dermoscopic features of AHM on other body sites, such as milky red areas, peripheral light brown structureless areas and linear irregular vessels. These features, asymmetric pigmented follicles and at RCM >= 3 atypical cells in five fields and focal follicular extension of atypical cells at DEJ may help in recognizing AHLM/LMM even when LM conventional features (e.g., obliteration of hair follicles under dermoscopy and large pagetoid cells under RCM) are absent or present only in very small areas of the lesion.

Glucose electrochemical sensors based on nanostructures of CuO/Cu(OH)2 onto graphene paper were prepared by thermal (solid) and nanosecond pulsed laser (molten phase) dewetting of a CuO layer 6 nm thin deposited by sputtering. Dewetted systems, obtained without the use of any binder, act as array of nanoelectrodes. Solid state and molten phase dewetting produce nanostructures of copper oxide-hydroxide with different average size, shape and surface composition. Molten phase dewetting originates particles with size below 100 nm, while solid state dewetting produces particles with average size of about 200 nm. Moreover, molten phase dewetting produce drop-shaped nanostructures, conversely nanostructures derived from solid state dewetting are multifaceted. X-ray photoelectron spectroscopy (XPS) characterization revealed that the surface of nanostructures is formed by a copper(II) species CuO and Cu(OH)2. Shape of anodic branch of the cyclic voltammograms of glucose in alkali solution evidenced a convergent diffusion mechanism. Analytical performances in amperometric mode are as good as or better than other sensors based on copper oxide. Amperometric detection of glucose was done at potential as low as 0.4 V versus saturated calomel electrode by both types of electrodes. Linear range from 50 μM to 10 mM, sensitivity ranging from 7 to 43 μA cm−2 mM−1 and detection limit of 7 μM was obtained. Good analytical performances were obtained by laser dewetted electrodes with a low copper content up to 1.2 by atoms percentage of the surface. Analytical performance of the proposed electrodes is compliant for the determination of glucose both in blood serum, saliva or tear.

A tri-metallic precursor mixture has been used to deposit Bi(1−x)DyxFeO3 film on conductive SrTiO3:Nb(100) substrates. A fine adjustment of the film composition is the key enabling an accurate tuning of the film piezoelectric and optical properties.

Implantable biomaterials play a key role for the success of orthopedic surgery procedures. However, infections remain one of the most damaging post-operative complications that lead to the implant failure. Recently, several approaches have been proposed to avoid or manage implant-associated infections. Among these, an appropriate surface functionalization to confer intrinsic antibacterial properties preserving the osteo-integration ability represents an appealing strategy for the development of innovative implant materials. Titanium and its alloys are the most used materials for manufacturing of both articular and bone skull prostheses as well as dental implants. However, to date there is still a significant clinical need to improve their bioactivity, osseointegration and antibacterial activity. In this study, titanium biomimetic scaffolds are prepared by nano-functionalization with TiO2 (Ti_TiO2) and γFe2O3 (Ti_γFe2O3). Both cytocompatibility and antibacterial activity have been evaluated. Data show that both nano-functionalized scaffolds exhibit a good antibacterial activity towards Staphylococcus aureus, reducing colony number to 99.4% (Ti_TiO2) and 99.9% (Ti_γFe2O3), respectively. In addition, an increase of both human adipose-derived mesenchymal stem cells (hADSCs) cell proliferation (up to 4.3-fold for Ti_TiO2 and 3.7-fold for Ti_γFe2O3) and differentiation has been observed. These data suggest that these nano-functionalized titanium substrates represent promising prototypes for new antimicrobial and osteoconductive biomaterials to be used in the orthopedic field to reconstruct significant bone defect.

In this work, multiferroic bismuth ferrite (BFO) was functionalized withmeso-tetraphenylporphine-4,4 ',4 '',4 '''-tetracarboxylic acid (TCPP). This new hybrid organic-inorganic material shows an enhanced photocatalytic activity for the degradation of organic dyes as it combines the properties of BFO which is an efficient visible light photocatalyst with peculiar porphyrin absorption in visible light. The anchoring of TCPP to the OH-terminations of the BFO surface through its carboxylic tethering groups was demonstrated using X-ray photoelectron spectroscopy and FT-IR spectroscopy. The photocatalytic activity of the material was also demonstrated through the photocatalytic degradation of Methylene Blue (MB) and Rhodamine-B (Rhd-B) in water under simulated solar light illumination. The TCPP molecules anchored to BFO slightly decrease (similar to 0.06 eV) the bandgap energy of the system and act as new catalytic centres, thus improving its photocatalytic activity. A photodegradation mechanism was also proposed. This new material is reusable and stable, as it maintains an unmodified photo-activity after several MB discoloration runs.

A novel metal organic framework (MOF)-based composite was synthesized on a Cu substrate via a two-step route. An amorphous iron oxide/hydroxide layer was first deposited on a Cu foil through a sol–...

Nanostructured materials represent a breakthrough in many fields of application. For sensing, the use of structures with high surface/volume ratio is crucial to obtain a good sensitivity. Chemical growth approaches are preferred to reach this goal but thick micrometers layers are usually needed. To reduce the layer thickness, methods are required to guaranteelarge exposed surfaces in a small volume. We have indeed designed new spongy TiO2 layers by a reactive sputtering method based on a grazing-incidence source combined with the local oxidation of the sputtered species (gig-lox). The process has been implemented with a doping procedure during growth consisting of adding in the reactive environment nitrogen at low flow rate in close proximity of the growing front. We have characterized the layers in terms of porosity, roughness and electrical behaviour with respect an undoped films. The doping procedure allowed improving the electrical response of the material with the best electrical performances achieved using 2 standard cubic centimeter per minute (sccm) of nitrogen. Unexpectedly, using a higher content of nitrogen is detrimental for the electrical response of the deposited layers.

Crystalline silicon-based heterojunction (HJ) solar cells are becoming the best choice for manufacturing companies, because of the low temperature processes useful for very thin silicon wafers and the possibility to easily achieve cells efficiencies higher than 22% on n-type silicon wafers. However, the maximum cell efficiency is still limited by the typical Fill Factor (FF) value of 82%. This issue is due to several factors, some of which are sometimes underestimated, like the base contact. Indeed, a potential mismatch between the work functions of the transparent conductive oxide and the base doped layer can give rise to a small barrier against electrons collection, which is not easy to recognize when the cell FF overcomes 80%. Also a low doping efficiency of the p-type amorphous layer at the emitter side can negatively affect the FF. In this case, even if high efficiency cells are produced, their full potential is still unexploited. Thus, both selective contacts of the cell, even if apparently optimized to achieve very good results, can hide problems that limit the final cell FF and efficiency. In a previous work, an experimental method and a model to individuate hidden barriers at the base contact on n-type crystalline silicon-based HJs have been provided. In this paper, that model is applied to experimental data obtained from the characterization of both commercial and laboratory level HJ solar cells. Moreover, an easy method to recognize the presence of a barrier to the charge transport at the emitter side of the cell is illustrated.

Combined treatments which use nanoparticles and drugs could be a synergistic strategy for the treatment of a variety of cancers to overcome drug resistance, low efficacy, and high-dose-induced systemic toxicity. In this study, the effects on human colon adenocarcinoma cells of surface modified Fe3O4 magnetic nanoparticles (MNPs) in combination with sodium butyrate (NaBu), added as a free formulation, were examined demonstrating that the co-delivery produced a cytotoxic effect on malignant cells. Two different MNP coatings were investigated: a simple polyethylene glycol (PEG) layer and a mixed folic acid (FA) and PEG layer. Our results demonstrated that MNPs with FA (FA-PEG@MNPs) have a better cellular uptake than the ones without FA (PEG@MNPs), probably due to the presence of folate that acts as an activator of folate receptors (FRs) expression. However, in the presence of NaBu, the difference between the two types of MNPs was reduced. These similar behaviors for both MNPs likely occurred because of the differentiation induced by butyrate that increases the uptake of ferromagnetic nanoparticles. Moreover, we observed a strong decrease of cell viability in a NaBu dose-dependent manner. Taking into account these results, the cooperation of multifunctional MNPs with NaBu, taking into consideration the particular cancer-cell properties, can be a valuable tool for future cancer treatment.

This paper reports on the first months of operation of the silicon heterojunction production line at Enel Green Power which started in April 2019 as well as strategies for efficiency improvement. The efficiency of the lines reached in short time is demonstrated in its current configuration with 4BB cell design. Within the collaboration with CEA, an intense activity is ongoing to increase the module efficiency. For the time being, it has been demonstrated a new European HJT cell record certified at 24.63% on a full M2 wafer.

In this paper we report the synthesis and characterization of biocompatible multi-functional magnetic nanoparticles (MNPs) able to enhance the intracellular transport of N-methylated drugs. The Fe3O4 magnetic core was first functionalized with a mixed monolayer consisting of two different phosphonic acids having terminal acetylenic and amino groups, which provide an active platform for further functionalization with organic molecules. Then, a tetraphosphonate cavitand receptor (Tiiii) bearing an azide moiety and the N-hydroxysuccinimide (NHS) activated forms of poly(ethylene glycol) (PEG), folic acid (FA) and carboxy-X-rhodamine (Rhod) were covalently anchored on alkyne and amine moieties respectively, through 1,3-dipolar cycloaddition and EDC/NHS coupling reactions. The obtained MNPs are biocompatible and possess magnetic, luminescence and recognition properties which make them suitable for multimodal theranostic applications. In particular, combined confocal microscopy and cytotoxicity experiments showed that these multi-functional MNPs are able to recognize a specific drug "in situ'' and promote its cellular internalization, thus enhancing its efficiency.

The synthesis of hybrid nano-composites in which an inorganic layer is grown on a polymeric surface via chemical bonds, is a challenging goal for many applications from photocatalysis, to sensing and optoelectronics. Herein, we describe on the growth of ZnO nanostructures by an Atomic Layer Deposition (ALD) technique on polyetherimide (poly(2,2'-bis(3,4-dicarboxyphenoxy) phenylpropane)-2phenylendiimide ULTEM (R) 1000) substrates. A surface modification consisting of a thermal photooxidization process, applied for different exposure times, has been properly performed on the polymer to promote the production of ALD suitable functionalities as reactive surface-sites. The chemical anchoring of the inorganic species from the gas-phase is demonstrated by spectroscopy and mass analyses to exclusively occur on the pre-oxidized films, whilst the ZnO growth does not occur in the untreated ULTEM (R) films in the operative ALD conditions. Notably, we demonstrate that two different regimes of growth take place in the oxidized polymer as a function of the photo-exposure time. In particular, the formation of a nanostructured coating of ZnO on the polyetherimide surface is found in the case of short-time photo-exposed polyetherimide (ALD-like regime), whilst an intermixed organic/polymer layer is found on the long-time oxidized films (Vapor Phase Infiltration, VPI-like regime). The photocatalytic activity of the synthesized materials has been tested through the degradation of methylene blue dye in aqueous solution under UV light irradiation, to give a proof of concept of a possible application of the nano-composites.

Green and alternative strategies for the preparation of silver nanoparticles (AgNP) are the focus of considerable attention, given their wide range of applications. A clean, eco-friendly, low-cost, scalable and straightforward protocol for the production of AgNP is reported, using hydrolyzed spent coffee grounds (HSCG) both as a reducing agent and a stabilizing matrix. The sample was easily recovered in 50–60% yield by centrifugation and lyophilization. Size and morphological analyses combined with X-ray diffraction analysis indicated ca. 6% w/w incorporation of AgNP of about 20 nm size into the HSCG matrix. AgNP-HSCG exhibited efficient antioxidant properties in several chemical assays and antimicrobial activities (MIC< 0.1 mg/mL) against Gram-negative bacteria such as E. coli and P. aeruginosa. Antibacterial devices made of chitosan films containing AgNP-HSCG were also prepared that showed significant inhibition zones against the same bacterial strains, even at the lowest loading (0.3% w/w) of AgNP, and remarkable antioxidant properties in aqueous media. An economic evaluation of the whole process was carried out, demonstrating that manufacturing of both HSCG and chitosan-based antibacterial devices is a convenient and easy-to-perform process, with the potential of full industrial scalability. Overall, the adopted circular approach, designed to reuse a cheap and abundant agri-food waste while avoiding the use of toxic or noxious chemicals, makes HSCG a practical and easily accessible multifunctional material for the clean and sustainable synthesis of AgNP with adequate size and stability for incorporation in efficient antioxidants and antimicrobial devices.

A hierarchical hybrid inorganic–organic system suited for the recognition of aromatic volatile organic compounds on brushlike ZnO fibers was synthetized. The hybrid material was obtained by a multistep approach based on the growth of ZnO nanorods onto electrospun ZnO fibers (average diameter 200 nm). The obtained nanostructured ZnO brushlike fibers (overall diameter 2 μm) were functionalized through the grafting of a bifunctional phosphonic linker (12-azidododecylphosphonic acid) followed by the anchoring of a specific cavitand receptor. The linker was anchored on ZnO fibers through the phosphonic group while the azide terminations reacted with a quinoxaline-bridged cavitand (QxCav) having four alkyne groups via “click” reaction. The anchoring steps were monitored through the evolution of the FT-IR features in the 3200–2800 cm–1 region due to C–Hx stretches and in the 2200–2000 cm–1 region due to the azide and alkyne groups of the phosphonic linker and QxCav. The recognition properties of this hybrid nano...

A novel hybrid photoactive material based on graphene foam (G) coupled with porphyrin-based polymers (Porph rings) was formulated by using a time-saving procedure to remove nickel from the final device. Specifically, Porph rings were spin coated onto the G platform with the double function of a visible-light photocatalyst and protective agent during nickel etching. The characterization of G-Porph rings was assessed by Scanning Electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and photoluminescence (PL). The novel material showed photocatalytic ability in degrading different classes of pollutants such as the herbicide 2,4 dichlorophenoxyacetic acid (2,4-D), polyethylene glycol (PEG) as an ingredient of care and health products, and also the methylene blue (MB) dye. UV-Vis spectroscopy, total organic carbon (TOC) and soft mass spectrometry techniques were used to monitor the photocatalytic process. The best performance in terms of photocatalytic efficiency was exhibited versus PEG and MB degradation. Furthermore, to determine the individual contribution of Reactive Oxygen Species (ROS) produced, free radical and hole scavenging tests were also carried out. Finally, a detailed map of the photocatalytic degradation mechanisms was proposed, reporting also the calculation of Porph rings' Highest Occupied Molecular Orbital (HOMO) and Lowest Occupied Molecular Orbital (LUMO) energy level values.

Zinc based nanostructures are very promising material for pH sensing since they allow the realization of low-cost, sustainable, and high sensitivity electrodes. The pH sensitivity reported in literature for different ZnO nanostructures spreads from sub- to super-Nernstian, with the microscopic mechanism behind the H+ detection often unrevealed. In this work we synthesize by hydrothermal process and thermal annealing two zinc based nanowalls (NWLs) consisting of layered hydroxide zinc nitrate Zn5(OH)8(NO3)2·2H2O (as grown) and zinc oxide ZnO (annealed) phases, respectively. Scanning electron microscopy, micro Raman spectroscopy, X-ray photoemission spectroscopy were used to characterize the morphology and structure of NWLs. Electrochemical chronopotentiometric analysis in standard buffer solutions (pH 4 to 9) was used to study the response towards pH. Despite the two zinc based NWLs have the same morphology (interconnected sheets 10-20 nm thin, 1.4–1.7 μm wide), truly different behavior as pH sensitive electrodes are evidenced. As grown NWLs show a super-Nernstian response (+83.7 mV/decade), whereas annealed NWLs show a sub-Nernstian response (+27.1 mV/decade). The data are satisfactorily modeled by considering the crystallographic structures and assuming that layered hydroxide zinc nitrate NWLs is sensitive to only H+ (with two simultaneous and independent mechanisms), while zinc oxide NWLs is simultaneously and independently sensitive to both H+ and OH−. These data and the proposed modeling are useful to further develop the pH sensitivity of electrodes based on ZnO nanostructures.

Octahedral crystals of Fe(III)-based Mil-101 and amino-functionalized Mil-101 are directly grown on Si(100) using easy solution routes under mild conditions. Images from microscopy analyses show th...

Combination of silicon heterojunction cell technology (SHJ) with bifacial module architecture is an appealing solution for manufactures who are focused on PV system performances. In this paper, we will present a study with an industrial perspective, initiated to address specific challenges of producing SHJ cells and modules in Europe. The impact of incoming wafer quality has been studied by analyzing at full ingot scale the efficiency performances of SHJ cells. The impact of long queue time prior to deposition is also reported. Finally, results of full size modules with 72 cells are presented.

We have realized tandem amorphous Si / microcrystalline Si PV cells and modules with an n+ SiOx emitter heterojunction with microcrystalline Si. The SiOx films show filamentary nanostructures and high electrical conductivity. Excellent photovoltaic characteristics are demonstrated.

The complexation between 2-ureido-4[1H]-pyrimidinone (UPy) and 2,7-diamido-1,8-naphthyridine (NaPy) is used to promote the mild chemisorption of a UPy-functionalized terbium(III) double decker system on a silicon surface. The adopted strategy allows the single-molecule magnet behavior of the system to be maintained unaltered on the surface.

A systematic study into the MOCVD of V-O films using the vanadyl-acetylacetonate [VO(acac)2] precursor is carried out. The films are prepared via low pressure MOCVD on Si(001) substrates. The nature and quality of films are examined by varying operational parameters, e.g., deposition temperature, precursor vaporization rate, and flow of oxygen reacting gas. X-ray diffraction data point to the formation of crystalline films in the range 200−550 °C. Outside of this temperature ranges amorphous phases were obtained. Field-emission scanning electron microscope (FESEM) images indicate very homogeneous surfaces with grain shape and dimensions depending on operational conditions. Energy dispersive X-ray (EDX) and X-ray photoelectron spectroscopy (XPS) analyses point to the absence of any C contamination.

Oxidation of volatile organic compounds (VOC) and preferential oxidation of CO in the excess of H2 (CO-PROX) were investigated over mono and bimetallic Au–Ag/CeO2 and Au–Cu/CeO2 catalysts. For the oxidation of VOC (2-propanol, ethanol and toluene) Au/CeO2 was the most active catalyst for the combustion of alcohols to CO2, Ag/CeO2 gave the best performance in the toluene total oxidation, Au–Ag/CeO2 and Au–Cu/CeO2 showed the highest selectivity to partial oxidation products. For CO-PROX Au–Ag/CeO2 and Au–Cu/CeO2 samples exhibited higher CO2 yield at low temperature than monometallic ones. The improved performance of bimetallic catalysts were accounted for an enhancement of surface ceria oxygens mobility caused by the addition of Ag or Cu to Au/CeO2 and involved in both investigated reactions. This effect was more evident on Au–Ag/CeO2 where a strong Au–Ag interaction occurred with formation of Au–Ag alloy or linked monometallic nanoparticles.

Pr1–xCaxMnO3 thin films have been deposited through an in situ metal organic chemical vapor deposition (MOCVD) process using a molten multi-metal source, consisting of the Pr(hfa)3·diglyme, Ca(hfa)2·tetraglyme, and Mn(tmhd)3 precursor mixture on single crystal substrates such as LaAlO3 (001) and MgO (001). Optimization of processing parameters has allowed the deposition of homogeneous thin films in morphology, composition, and thickness. The effect of substrate has been assessed in relation to structure and morphology. Field emission scanning electron microscope of a Pr0.7Ca0.3MnO3 film deposited at 1000 °C on MgO (001).