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The enhancement of precipitation over the mountain regions of Southern California, in conjunction with mesoscale and synoptic-scale forcings, can result in high-intensity, short-duration extreme precipitation events (EPEs) that are often associated with hazardous impacts. In this study, candidate upstream atmospheric precursors at relevant spatiotemporal scales to such hazards are explored using a WRF mesoscale model with 5-km grid spacing and an hourly temporal resolution. This high-resolution model, once validated against observations, is used to discern statistically significant physics-based signals between hypothetical mesoscale forcings and the modeled precipitation response. Specifically, the role of upstream instability in modeled EPEs is indexed by convective available potential energy (CAPE) and is examined for two mountainous regions of Southern California at several lag times. A Monte Carlo approach reveals statistically significant differences between the relationship of CAPE associated with EPEs in comparison to the analogous relationship for any precipitation event. These findings hold even with accounting for the well-established role of favorably oriented low-level moisture flux in orographic precipitation. This could indicate that atmospheric instability plays a role in providing additional lifting mechanisms, in conjunction with orographic and synoptic-scale forcings, to facilitate the high short-duration precipitation intensities that have been observed in the region. This diagnostic exploratory study provides additional candidate indicators of predictability of such EPEs at higher spatiotemporal scales than previous work, based on mesoscale model physics. Further analysis should examine the identified precursors using observational data with adequate resolution.

Abstract: The ubiquity of the obesity condition in the United States, Europe and other regions with developed economies will associate to a significant adverse impact on public health. Numerous data indicate that social, behavioral, neuroendocrine, and metabolic factors may encourage compulsive eating behaviors thus increasing the risk of obesity. Several pathological conditions overlap with excess weight. Among the most common, there are binge eating disorder (BED) and food addiction (FA), which share several neurobiological and behavioral aspects with substance addictions. BED has many features in common with addictive behavior, such as loss of control and the need to frequently repeat the dysfunctional pattern despite negative consequences. The food addiction hypothesis assumes that exposure to highly palatable foods alters the reward circuits of the brain, resulting in a behavioral phenotype similar to substance addiction and facilitating dysfunctional eating behaviors, such as binge eating crises. In this review, over 100 publications, researched on MEDLINE from 2000 until march 2021, were included since they evaluate neuroendocrine changes, emotional homeostatic factors and the reward circuit, associating them with exposure to highly palatable foods, loss of control, the way we eat, the increase in impulsiveness and the inability to change eating behavior despite the negative consequences related to overweight and obesity. Finally, understanding the underlying neurobiological circuits of compulsive eating behaviors and food addiction could result in a great therapeutic potential for patients suffering from ailments nutrition and obesity.

After an introductory chapter on the quantum supersymmetric string, in which particular attention will be devoted to the techniques via which phenomenologically viable models can be obtained from the ultraviolet microscopic degrees of freedom, and a brief review of the swampland program, the technical tools required to deal with geometric flows will be outlined. The evolution of a broad family of scalar and metric bubble solutions under Perelman's combined flow will be then discussed, together with their asymptotic behaviour. Thereafter, the geometric flow equations associated to a generalised version of Perelman's entropy function will be derived and employed in defining the action-induced flow associated to a given theory for a scalar field and a dynamical metric. The problem of preserving Einstein field equations along the corresponding moduli space trajectories will be cured by allowing a supplementary energy-momentum tensor term to appear along the flow. In a particular example, such contribution will be shown to precisely reproduce the infinite tower of states with exponentially dropping masses postulated by the distance conjecture., 175 pages

The final steps of lagging strand synthesis induce maturation of Okazaki fragments via removal of the RNA primers and ligation. Iterative cycles between Polymerase δ (Polδ) and Flap endonuclease-1 (FEN1) remove the primer, with an intermediary nick structure generated for each cycle. Here, we show that human Polδ is inefficient in releasing the nick product from FEN1, resulting in non-processive and remarkably slow RNA removal. Ligase 1 (Lig1) can release the nick from FEN1 and actively drive the reaction toward ligation. These mechanisms are coordinated by PCNA, which encircles DNA, and dynamically recruits Polδ, FEN1, and Lig1 to compete for their substrates. Our findings call for investigating additional pathways that may accelerate RNA removal in human cells, such as RNA pre-removal by RNase Hs, which, as demonstrated herein, enhances the maturation rate ~10-fold. They also suggest that FEN1 may attenuate the various activities of Polδ during DNA repair and recombination.

Renewable energy sources such as photovoltaic (PV) technologies are considered to be key drivers towards climate neutrality. Thin-film PVs, and particularly copper indium gallium selenide (CIGS) technologies, will play a crucial role in the turnaround in energy policy due to their high efficiencies, high product flexibility, light weight, easy installation, lower labour-intensiveness, and lower carbon footprint when compared to silicon solar cells. Nonetheless, challenges regarding the CIGS fabrication process such as moderate reproducibility and process tolerance are still hindering a broad market penetration. Therefore, cost-efficient and easily implementable in-line process control methods are demanded that allow for identification and elimination of non-conformal cells at an early production step. As part of this work, a practical approach towards industrial in-line photoluminescence (PL) imaging as a contact-free quality inspection tool is presented. Performance parameters of 10 CIGS samples with 32 individually contacted cells each were correlated with results from PL imaging using green and red excitation light sources. The data analysis was fully automated using Python-based image processing, object detection, and non-linear regression modelling. Using the red excitation light source, the presented PL imaging and data processing approach allows for a quantitative assessment of the cell performance.

The HYDROCOASTAL projectaims to enhance our understanding of interactions between the inland water and coastal zone, between the coastal zone and the open ocean, and the small-scale processes that govern these interactions.To achieve these aims, the HYDROCOASTAL project team has developed and implemented new SAR altimeter processing algorithms for the coastal zone and inland waters, and with these processed Sentinel 3A, 3B and Cryosat-2 data to generate an initial 2-year Test Data Set for selected regions. The performance of these new algorithms has been evaluated, by statistical analyses and comparison against in situ data. From this analysis, the best performing algorithms have been identified and implemented in a processing scheme to generate a global scale coastal zone and inland water SAR altimeter data setA series of case studies have assessed these products in terms of their scientific impacts.All the produced data sets will be available on request to external researchers, and full descriptions of the processing algorithms are available via the project web-site.The presentation will provide an overview of the project, and present key results from the coastal zone studies, which have investigated the potential scientific impact and benefits of the new data set in understanding processes in six different coastal regions, including the Severn Estuary in the UK; The German Bight, Southern Baltic and Elbe Estuary; The Venice Lagoon; The Thailand Coast; The Ebro River and Delta, and the Wadden Sea., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Sea surface wind forecasts in the Adriatic Sea often suffer for unadequate modelling, especially for the wind speed. This has detrimental effects on the accuracy of sea level and storm surge predictions. We present a numerical method to reduce the bias between the sea surface wind observed by the scatterometers and that supplied by the European Centre for Medium-Range Weather Forecasts (ECMWF) global atmospheric model, for storm surge forecasting applications. The method, called “wind bias mitigation”, relies on scatterometer observations to determine a multiplicative factor ∆ws which modulates the standard model wind in order to decrease the bias between scatterometer and model. We compare four different mathematical approaches to this method, for a total of eight different formulations of the multiplicative factor ∆ws. Four datasets are used for the assessment of the eight different bias mitigation methods: a collection of 29 Storm Surge Events (SEVs) cases in the years 2004-2014, a collection of 48 SEVs in the years 2013-2016, a collection of 364 cases of random sea level conditions in the same period, and a collection of the seven SEVs in 2012-2016 that were worst predicted by the Centro Previsioni e Segnalazioni Maree, Comune di Venezia (Tide Forecast and Early Warning Centre of the Venice Municipality - CPSM). The statistical analysis shows that the bias mitigation procedures supplies a mean wind speed more accurate than the standard forecast, when compared with scatterometer observations, in more than 70% of the analyzed cases.

During lagging strand synthesis, DNA Ligase 1 (Lig1) cooperates with the sliding clamp PCNA to seal the nicks between Okazaki fragments generated by Pol δ and Flap endonuclease 1 (FEN1). We present several cryo-EM structures combined with functional assays, showing that human Lig1 recruits PCNA to nicked DNA using two PCNA-interacting motifs (PIPs) located at its disordered N-terminus (PIPN-term) and DNA binding domain (PIPDBD). Once Lig1 and PCNA assemble as two-stack rings encircling DNA, PIPN-term is released from PCNA and only PIPDBD is required for ligation to facilitate the substrate handoff from FEN1. Consistently, we observed that PCNA forms a defined complex with FEN1 and nicked DNA, and it recruits Lig1 to an unoccupied monomer creating a toolbelt that drives the transfer of DNA to Lig1. Collectively, our results provide a structural model on how PCNA regulates FEN1 and Lig1 during Okazaki fragments maturation., This research was supported by King Abdullah University of Science and Technology through core funding (to S.M.H. and A.D.B.) and the Competitive Research Award Grant CRG8 URF/1/4036‐01‐01 (to S.M.H. and A.D.B.). We acknowledge The Midlands Regional Cryo-EM Facility at the Leicester Institute of Structural and Chemical Biology (LISCB), major funding from MRC (MC_PC_17136). We thank Christos Savva and T.J. Ragan (LISCB, University of Leicester) for their help in cryo-EM data collection and advice on data processing. This project has been carried out using the resources of CSUC.

Background Immune checkpoint inhibitors (ICI) have revolutionized the clinical management of a broad spectrum of solid and hematopoietic malignancies over the past decade. ICI are associated with several Immune-related Adverse Events, among which myocarditis and atrioventricular blocks are uncommon but potentially fatal toxicities. Material and Methods We describe two patients undergoing treatment with PD-1 checkpoint inhibitors for metastatic cancers who developed myositis and myocarditis complicated by complete atrioventricular block (CAVB). The first patient had a history of metastatic sarcomatoid urothelial carcinoma treated with Pembrolizumab. After two cycles, he developed eyelid ptosis and was hospitalized for syncopal episodes due to CAVB associated with ICI myocarditis. The second patient had a history of metastatic melanoma and was hospitalized for myocarditis and myositis after the second infusion of Nivolumab. Results In the first case, high-dose corticosteroid therapy was promptly initiated, with subsequent rapid recovery of sinus rhythm and rapid resolution of symptoms. The second patient, despite high-dose corticosteroid therapy, developed CAVB requiring implantation of a definitive PM. After initiation of mycophenolate mofetil and intravenous immunoglobulin therapy, gradual recovery was observed. Both patients had normal left ventricular function with no wall motion abnormalities. However, speckle tracking echocardiography revealed a normal global longitudinal left ventricular strain (GLS) of -19.8% in patient 1 and a depressed GLS of -14.7% in patient 2, consistent with the different evolution of the two myocarditis. Conclusions We recommend a high degree of caution and awareness to all physicians when treating immunotherapy patients. Myocarditis is a relatively rare but potentially fatal event due to its early onset, non-specific clinical presentation and fulminant progression. GLS may be useful in detecting myocardial damage in these patients. Discontinuation of ICI, cardiac pacing, treatment with high-dose corticosteroids and immunosuppressive agents may improve the outcome.

Background Vaccination represents a cornerstone of prevention in the COVID-19 pandemic. Rare adverse events including acute pericarditis and myopericarditis have been reported. Material and Methods All consecutive patients referred to our referral center for pericardial diseases following COVID-19 vaccination from 1st April 2021 to 15th April 2022 were included. Acute pericarditis and myopericarditis were diagnosed according to ESC guidelines. Patients with SARS-CoV-2 infection were excluded from the study. Results Twenty-four patients (79% males) aged 39.7 ± 19.8 years were referred to our center with pericarditis after receiving COVID-19 vaccination. 13 (54%) patients were diagnosed with myopericarditis. The mean time between vaccination and symptoms onset was 7.0 ± 4.9 days and the most frequent symptom was pericarditic chest pain (83%). Respectively, 50% and 33% of patients presented after the second and the third dose of the vaccine. Almost all patients were treated with both nonsteroidal anti-inflammatory drugs and colchicine. Five patients (21%) experienced a recurrence of pericarditis. No patient died or developed constrictive pericarditis. Mean follow-up was 8.0 ± 3.2 months. Conclusions COVID-19 vaccine-related pericarditis typically manifest with mild clinical signs, in young males, a few days after the second or third vaccine dose and are commonly characterized by a rapid complete recovery. Despite these rare side effects, the benefits of COVID-19 vaccination clearly outweigh the limited risk of pericarditis and myocarditis, and vaccination is strongly recommended to prevent COVID-19 infection, transmission and related complications.

Background Pericarditis and pericardial effusion (PE) are rare but potentially life-threatening complications in chronic graft-vs-host disease (cGVHD). Limited data are currently available in this setting, based on small single-center retrospective studies. The purpose of this study is to characterize the clinical presentation, management, and outcomes of pericarditis and PE complicating cGVHD in allogeneic hematopoietic cell transplant recipients. Material and Methods We included all consecutive patients referred to our pericardial diseases referral center from 1st May 2008 to 1st May 2022. All patients had no previous cardiovascular or autoimmune diseases and suffered from severe cGVHD with involvement of at least 2 organs. Pericarditis and PE were diagnosed according to ESC guidelines. Conditioning-related toxicity and infections were carefully excluded. Results Pericarditis was diagnosed in 4 patients (2 males, mean age 48.5 ±9.0 years), of whom 2 developed mild PE. PE without pericarditis was diagnosed in 5 patients (80% male, aged 53.2 ±8.9 years), in 2 patients it was reported as severe, requiring pericardial drainage. The average time after allogeneic hematopoietic stem cell transplantation was 22 months (range, 4 to 58 months). All patients required escalation of the corticosteroid therapy they were chronically taking, and in 4 cases the therapy was boosted with non-steroidal anti-inflammatory drugs. Only one patient developed a recurrence and died of multiorgan failure associated with severe cGVHD (involving eyes, mucous membranes, skin, joints, liver, pleuro-pericardial effusion) refractory to immunosuppressive therapy. Overall survival was 89% and no patient developed constrictive pericarditis. Mean follow-up was 69±55 months. Conclusions Pericarditis and PE related to cGVHD typically occur with mild clinical signs in the context of severe cGVHD, however in our study 22% of patients required pericardial drainage at diagnosis. The mainstay of treatment is high-dose steroids and usually the majority of patients have a favorable outcome.

Background Cardiac tamponade complicates 18,7% of patients with type A aortic dissection and is associated with dramatically worse outcome and a nearly doubling of in-hospital mortality. Immediate surgical repair with intra-operative pericardial drainage is the treatment of choice. Nevertheless, the management of unstable patients who cannot undergo cardiac surgery in short time is controversial. Case report Here we present a case report of an 82-year woman with type A aortic dissection complicated by cardiac tamponade. The patient alerted the emergency system because of a sudden epigastric pain. On her arrival to the hospital, her systolic blood pressure was 50 mmHg; despite intravenous fluids and inotropic support, she remained hypotensive. Transthoracic echocardiography revealed an intimal flap involving ascending aorta and aortic arch, and a hemodynamically significant pericardial effusion. Immediate surgical repair was not possible due to the lack of available operating rooms. To stabilize the patient, percutaneous pericardiocentesis from apical approach was attempted, unsuccessfully. A second attempt of percutaneous pericardiocentesis was made from substernal approach, with removal of just 150 cc of pericardial fluid and insertion of a pigtail drainage catheter. Thanks to this procedure systolic blood pressure raised up to 100 mmHg and the patient was stabilized. A CT Angiography scan was performed, showing an aortic dissection extending from the aortic valvular plane to the origin of the right iliac artery. The patient maintained hemodynamical stability until surgical intervention, which started four hours later her arrival. The patient underwent substitution of ascending aorta, aortic hemiarch, non-coronary sinus and aortic valve. There were no complications related to the pericardial drainage and in 34th post-operative day she was discharged in good condition. Conclusion Percutaneous pericardiocentesis should be considered in unstable patients with type A dissection complicated by cardiac tamponade who cannot await surgical treatment, providing that very small amount of pericardial fluid is removed, in order to maintain systolic blood pressure around 90 mmHg.

In this work, the problem of constructing geometric flow equations that preserve Einstein field equations for the spacetime metric is addressed. After having briefly discussed the main features of Ricci flow, the on-shell flow equations for a system comprised of a dynamical metric and a set of matter fields are constructed. Then, two examples in which the matter content is just a single, self-interacting scalar field are analysed in detail, imposing the geometric flow equations to be the action-induced ones. In conclusion, an explicit connection to the Swampland Distance Conjecture is proposed., 72 pages, 18 figures

Background and aims: Familial hypercholesterolaemia (FH) is a powerful risk factor for cardiovascular (CV) events. High levels of low-density lipoprotein cholesterol (LDL-C) since birth are linked to the early onset of atherosclerotic disease. A genetic mutation determining FH is present in about one subject out of 250; FH should be more represented among subjects with a documented diagnosis of coronary artery disease (CAD). The POSTER Study evaluated the prevalence of FH in Italian patients with a recent CAD event. Methods: Eighty-two cardiology centres enrolled patients with a documented CAD event; CV risk profile, drug therapy and biochemical parameters were collected. Dutch Lipid Clinic Network (DLCN) criteria were used to define patients with a potential FH diagnosis (score ≥6); these patients underwent molecular testing for genetic diagnosis of FH. Results: Overall, 5415 patients were enrolled and the main index events were myocardial infarction with ST-elevation, non ST-elevation acute coronary syndrome (ACS), or a recent coronary revascularization (34.8%, 37.2%, and 28% respectively). Mean age was 66 ± 11 years, men were 78%; about 40% were already treated with statins, proportion that increased after the acute event (96.5%). Based on the DLCN score, the prevalence of potential FH was 5.1%, 0.9% of them had a diagnosis of definite FH (score >8). These patients were younger than patients with a score 190 mg/dL. FH was genetically confirmed in 42 subjects (15.9%); genetic diagnosis was defined as not conclusive for FH in 63 patients (23.9%). Finally, in 159 subjects (60.2%) no pathogenic mutations in the tested genes were identified, defining them as negative for monogenic familial hypercholesterolemia. Conclusions: Results underscore a relatively high prevalence of potential FH in patients with a recent CAD event. Therefore, an early identification of these subjects may help improve the management of their high CV risk and, by cascade screening, identify possible FH relatives.

Background and purpose Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013. Graphical abstract

Y-family DNA polymerase κ (Pol κ) can replicate damaged DNA templates to rescue stalled replication forks. Access of Pol κ to DNA damage sites is facilitated by its interaction with the processivity clamp PCNA and is regulated by PCNA mono-ubiquitylation. Here, we present cryo-EM reconstructions of human Pol κ bound to DNA, an incoming nucleotide, and wild type or mono-ubiquitylated PCNA (Ub-PCNA). In both reconstructions, the internal PIP-box adjacent to the Pol κ Polymerase-Associated Domain (PAD) docks the catalytic core to one PCNA protomer in an angled orientation, bending the DNA exiting the Pol κ active site through PCNA, while Pol κ C-terminal domain containing two Ubiquitin Binding Zinc Fingers (UBZs) is invisible, in agreement with disorder predictions. The ubiquitin moieties are partly flexible and extend radially away from PCNA, with the ubiquitin at the Pol κ-bound protomer appearing more rigid. Activity assays suggest that, when the internal PIP-box interaction is lost, Pol κ is retained on DNA by a secondary interaction between the UBZs and the ubiquitins flexibly conjugated to PCNA. Our data provide a structural basis for the recruitment of a Y-family TLS polymerase to sites of DNA damage., This research was supported by King Abdullah University of Science and Technology through core funding (to S.M.H.) and the Competitive Research Award Grant CRG8 URF/1/4036‐01‐01 (to S.M.H. and A.D.B.), and by the Wellcome Trust (to A.D.B.). R.C. acknowledges funding from the MINECO (CTQ2016-78636-P) and to AGAUR, (2017 SGR 324). The MD project has been carried out using CSUC resources. We acknowledge The Midlands Regional Cryo-EM Facility at the Leicester Institute of Structural and Chemical Biology (LISCB), major funding from MRC (MC_PC_17136). We thank Christos Savva (LISCB, University of Leicester) for his help in cryo-EM data collection and advice on data processing.

Mediastinal teratoma rarely causes pericarditis. We report a case of a 22-year-old young female admitted to the emergency department for inspiratory chest pain and fever with severe pericardial effusion, unexepectable the cause of pericarditis was a mediastinal teratoma.

Ricci flow is a natural gradient flow of the Einstein-Hilbert action. Here we consider the analog for the Einstein-Maxwell action, which gives Ricci flow with a stress tensor contribution coupled to a Yang-Mills flow for the Maxwell field. We argue that this flow is well-posed for static spacetimes with pure electric or magnetic potentialsand show it preserves both non-extremal and extremal black hole horizons. In the latter case we find the flow of the near horizon geometry decouples from that of the exterior. The Schwarzschild black hole is an unstable fixed point of Ricci flow for static spacetimes. Here we consider flows of the Reissner-Nordstr\"om (RN) fixed point. The magnetic RN solution becomes a stable fixed point of the flow for sufficient charge. However we find that the electric RN black hole is always unstable. Numerically solving the flow starting with a spherically symmetric perturbation of a non-extremal RN solution, we find similar behaviour in the electric case to the Ricci flows of perturbed Schwarzschild, namely the horizon shrinks to a singularity in finite time or expands forever. In the magnetic case, a perturbed unstable RN solution has a similar expanding behaviour, but a perturbation that decreases the horizon size flows to a stable black hole solution rather than a singularity. For extremal RN we solve the near horizon flow for spherical symmetry exactly, and see in the electric case two unstable directions which flow to singularities in finite flow time. However, even turning these off, and fixing the near horizon geometry to be that of RN, we numerically show that the flows appear to become singular in the vicinity of its horizon., Comment: 46 pages, 12 figures

In the following work, an attempt to conciliate the Ricci flow conjecture and the Cobordism conjecture, stated as refinements of the Swampland distance conjecture and of the No global symmetries conjecture respectively, is presented. This is done by starting from a suitable manifold with trivial cobordism class, applying surgery techniques to Ricci flow singularities and trivialising the cobordism class of one of the resulting connected components via the introduction of appropriate defects. The specific example of $\Omega^{SO}_4$ is studied in detail. A connection between the process of blowing up a point of a manifold and that of taking the connected sum of such with $\mathbb{CP}^n$ is explored. Hence, the problem of studying the Ricci flow of a $K3$ whose cobordism class is trivialised by the addition of $16$ copies of $\mathbb{CP}^2$ is tackled by applying both the techniques developed in the previous sections and the classification of singularities in terms of ADE groups., Comment: 52 pages, 2 figures

Aims: Vaccination represents a cornerstone of prevention in the COVID-19 pandemic. Rare adverse events including acute pericarditis and myopericarditis have been reported. Methods: All consecutive patients referred to our referral center for pericardial diseases following COVID-19 vaccination from 1 April 2021 to 15 April 2022 were included. Acute pericarditis and myopericarditis were diagnosed according to ESC guidelines. Patients with SARS-CoV-2 infection were excluded from the study. Results: Twenty-four patients (79% men) aged 39.7 ± 19.8 years were referred to our center with pericarditis after receiving COVID-19 vaccination. Thirteen (54%) patients were diagnosed with myopericarditis. The mean time between vaccination and symptoms onset was 7.0 ± 4.9 days, and the most frequent symptom was pericarditic chest pain (83%). Respectively, 50 and 33% of patients presented after the second and the third dose of the vaccine. Almost all patients were treated with both nonsteroidal anti-inflammatory drugs and colchicine. Five patients (21%) experienced a recurrence of pericarditis. No patient died or developed constrictive pericarditis. Mean follow-up was 8.0 ± 3.2 months. Conclusion: COVID-19 vaccine-related pericarditis typically manifest with mild clinical signs, in young male individuals, a few days after the second or third vaccine dose and are commonly characterized by a rapid complete recovery.

Cardiomyocyte renewal represents an unmet clinical need for cardiac regeneration. Stem cell paracrine therapy has attracted increasing attention to resurge rescue mechanisms within the heart. We previously characterized the paracrine effects that human amniotic fluid–derived stem cells (hAFSC) can exert to provide cardioprotection and enhance cardiac repair in preclinical models of myocardial ischemia and cardiotoxicity. Here, we analyze whether hAFSC secretome formulations, namely, hAFSC conditioned medium (hAFSC-CM) over extracellular vesicles (hAFSC-EVs) separated from it, can induce cardiomyocyte renewal. c-KIT+ hAFSC were obtained by leftover samples of II trimester prenatal amniocentesis (fetal hAFSC) and from clinical waste III trimester amniotic fluid during scheduled C-section procedures (perinatal hAFSC). hAFSC were primed under 1% O2 to enrich hAFSC-CM and EVs with cardioactive factors. Neonatal mouse ventricular cardiomyocytes (mNVCM) were isolated from cardiac tissue of R26pFUCCI2 mice with cell cycle fluorescent tagging by mutually exclusive nuclear signal. mNVCM were stimulated by fetal versus perinatal hAFSC-CM and hAFSC-EVs to identify the most promising formulation for in vivo assessment in a R26pFUCCI2 neonatal mouse model of myocardial infarction (MI) via intraperitoneal delivery. While the perinatal hAFSC secretome did not provide any significant cardiogenic effect, fetal hAFSC-EVs significantly sustained mNVCM transition from S to M phase by 2-fold, while triggering cytokinesis by 4.5-fold over vehicle-treated cells. Treated mNVCM showed disorganized expression of cardiac alpha-actinin, suggesting cytoskeletal re-arrangements prior to cell renewal, with a 40% significant downregulation of Cofilin-2 and a positive trend of polymerized F-Actin. Fetal hAFSC-EVs increased cardiomyocyte cell cycle progression by 1.8-fold in the 4-day-old neonatal left ventricle myocardium short term after MI; however, such effect was lost at the later stage. Fetal hAFSC-EVs were enriched with a short isoform of Agrin, a mediator of neonatal heart regeneration acting by YAP-related signaling; yet in vitro application of YAP inhibitor verteporfin partially affected EV paracrine stimulation on mNVCM. EVs secreted by developmentally juvenile fetal hAFSC can support cardiomyocyte renewal to some extension, via intercellular conveyance of candidates possibly involving Agrin in combination with other factors. These perinatal derivative promising cardiogenic effects need further investigation to define their specific mechanism of action and enhance their potential translation into therapeutic opportunity.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): University of Genova Background Reactivation of cardiomyocyte renewal represents a milestone for cardiac regeneration. While broadly active in the early neonatal mammalian myocardium, such mechanism is lost soon after birth, with transition to defective repair. We previously showed that human amniotic fluid stem cells (hAFS) possess cardioprotective and cardioactive paracrine potential in a preclinical adult mouse model of myocardial infarction (MI)1, by sustaining cardiomyocyte cell cycle re-entry up to DNA duplication. Purpose Here we analyse whether hAFS secretome formulations, namely hAFS-conditioned medium (hAFS-CM) over extracellular vesicles (hAFS-EVs) separated from that, can enhance cardiomyocyte renewal in vitro and in vivo. Methods hAFS were obtained by leftover samples of prenatal screening amniocentesis and primed under 1% O2 preconditioning to enrich hAFS-CM and hAFS-EVs with cardioactive factors. hAFS-EVs were concentrated from hAFS-CM by serial ultracentrifugation. hAFS-EVs were profiled by electron microscopy, nanoparticle tracking analysis, proteomics and RNA sequencing (RNAseq). Neonatal mouse ventricular cardiomyocytes (mNVCM) were enzymatically isolated from R26pFUCCI2 mice with fluorescent tagging of cell-cycle by nuclear signal (G1-phase by Cdt1-mCherry; S-G2-M-phases by Geminin-mVenus1)2. mNVCM were stimulated by hAFS-CM or hAFS-EVs to identify the most promising formulation for further analysis in a R26pFUCCI2 4-day-old MI mouse model via intra-peritoneal delivery, according to principles of laboratory animal care and in compliance with authorization from the Italian Ministry of Health. Results hAFS-EVs sustained R26pFUCCI2 mNVCM transition from S- to M-phase by 2.1-fold (*p Conclusions Our current findings suggest that EVs secreted by developmentally juvenile hAFS may be endowed with relevant potential to support cardiomyocyte renewal for future paracrine therapy in regenerative medicine with putative molecular candidate(s) of action in their cargo content including Agrin and non-coding miRNAs.

Food extract’s biological effect and its improvement using nanotechnologies is one of the challenges of the last and the future decades; for this reason, the antioxidant effect of scarlet eggplant extract liposomal incorporation was investigated. Scarlet eggplant (Solanum aethiopicum L.) is a member of the Solanaceae family, and it is one of the most consumed vegetables in tropical Africa and south of Italy. This study investigated the antioxidant activity and the phytochemical composition of S. aethiopicum grown in the Basilicata Region for the first time. The whole fruit, peel, and pulp were subjected to ethanolic exhaustive maceration extraction, and all extracts were investigated. The HPLC-DAD analysis revealed the presence of ten phenolic compounds, including hydroxycinnamic acids, flavanones, flavanols, and four carotenoids (one xanthophyll and three carotenes). The peel extract was the most promising, active, and the richest in specialized metabolites; hence, it was tested on HepG2 cell lines and incorporated into liposomes. The nanoincorporation enhanced the peel extract’s antioxidant activity, resulting in a reduction of the concentration used. Furthermore, the extract improved the expression of endogenous antioxidants, such as ABCG2, CAT, and NQO1, presumably through the Nrf2 pathway.

In this article, the name of the GLORIA-AF investigator Anastasios Kollias was given incorrectly as Athanasios Kollias in the Acknowledgements. The original article has been corrected.

Background: To date, no study has been performed on the relationship between depression and perimenopausal symptoms using the Path model in Iran. Objective: This study aims to assess the relationship between depression and menopause symptoms using the PATH model. Methods: A cross-sectional study was conducted for 4 months, in 2019, and 332 menopausal women were enrolled in 14 public health centers. Data collection instruments included questionnaires of demographic characteristics, anxiety instrument, Menopause Rating Scale, and the Beck Depression short Inventory (BDI-S). The hypothesized mediators were assessed using Structural Equation Modeling (SEM). The model included depression symptoms (dependent variable), anxiety (mediators), number of alive children (moderator), and menopausal symptoms (independent variable). Analyses were conducted by SPSS 16 and AMOS 20. Results: There was a significant positive correlation between menopause symptoms with total anxiety (Rs=0.52), state anxiety (Rs=0.47), trait anxiety (Rs=0.46), and depression (Rs=0.54). Depression had a significant positive correlation with total anxiety (Rs=0.64), trait anxiety (Rs=0.58), and state anxiety (Rs=0.59). Also, the total mediating effect of total anxiety and depression and the total moderating effect of the number of alive children were significant on menopause symptoms. Conclusion: According to the results of the present study, there is an association between depression and menopausal symptoms. Therefore, health providers should pay more attention to the psychological health of women during the perimenopausal period. The predictor factors should be considered in both intervention and clinical assessment of menopause women.

Although iatrogenic damage is less often involved, deep nerve injuries are reported especially as a result of small saphenous vein (SSV) dissection. Complete or partial division of the common peroneal nerve (CPN) during varicose vein operations causes substantial and serious disability. Most CPN injuries recover spontaneously; nonetheless, some require nerve surgery. Treatment depends on the nature of CPN injury. This report chronicles 2 instances of CPN injury after SSV surgery, addressing treatment strategies and therapeutic gains. The pertinent literature is also reviewed.

Prepectoral prosthetic breast reconstruction has been widely reassessed in recent years and is taking on an increasingly important role in the field of immediate breast reconstruction. We report here a case series of 32 patients who underwent nipple-sparing mastectomy for breast carcinoma and prepectoral breast reconstruction involving an acellular dermal matrix (ADM) treated by means of a skin-graft mesher in our hospital from January 2015 to March 2016. The indications for this type of reconstruction were body mass index (BMI) less than 30 kg/m2; no history of radiotherapy; no active smokers; moderate grade breast; and good viability of mastectomy flap: normal skin colour, active bleeding at the fresh cut edges, and thicker than 1 cm mastectomy flaps; the viability of lower thicknesses was ascertained by the fluorescent dye indocyanine green xenon-based imaging technology (4 patients). The mean age of the patients was 56.4 years (range: 39-77 years). Their mean BMI was 27.4 kg/m2. Until the end of follow-up (mean: 17 months), major complications requiring reoperation occurred in 9% of patients and minor complications in 22% of patients. The mean of the 3 pain visual analogue scale scores taken in the first 24 hours after surgery was 1.8. Mean duration of hospital stay has been 2.2 days. Our complication rate was similar to those reported in other studies on prepectoral breast reconstruction featuring total ADM coverage of the implant.

Background:: Gender dysphoria is a clinical condition in which a state of inner suffering, stress and anxiety is detected when biological sex and a person's gender identity do not coincide. People who identify themselves as transgender people are more vulnerable and may have higher rates of dissatisfaction with their bodies which are often associated with a disorderly diet in an attempt to change the bodily characteristics of the genus of birth and, conversely, to accentuate the characteristics of the desired sexual identity. Aim:: The purpose of this work is to examine the association between dissatisfaction with one's own body and eating and weight disorders in people with gender dysphoria. Results:: Gender dysphoria and eating disorders are characterized by a serious discomfort to the body and the body suffers in both conditions. The results of our study suggest that rates of pathological eating behaviors and symptoms related to a disordered diet are high in patients with gender dysphoria and that standard screening for these symptoms must be considered in both populations at the time of evaluation and during the course of the treatment. Conclusions:: In light of this evidence, clinicians should always investigate issues related to sexuality and gender identity in patients with eating disorders, to develop more effective prevention measures and better strategies for therapeutic intervention..

In eukaryotes, DNA polymerase δ (Pol δ) bound to the proliferating cell nuclear antigen (PCNA) replicates the lagging strand and cooperates with flap endonuclease 1 (FEN1) to process the Okazaki fragments for their ligation. We present the high-resolution cryo-EM structure of the human processive Pol δ–DNA–PCNA complex in the absence and presence of FEN1. Pol δ is anchored to one of the three PCNA monomers through the C-terminal domain of the catalytic subunit. The catalytic core sits on top of PCNA in an open configuration while the regulatory subunits project laterally. This arrangement allows PCNA to thread and stabilize the DNA exiting the catalytic cleft and recruit FEN1 to one unoccupied monomer in a toolbelt fashion. Alternative holoenzyme conformations reveal important functional interactions that maintain PCNA orientation during synthesis. This work sheds light on the structural basis of Pol δ’s activity in replicating the human genome., Pol δ bound to the proliferating cell nuclear antigen (PCNA) replicates the lagging strand in eukaryotes and cooperates with flap endonuclease 1 (FEN1) to process the Okazaki fragments for their ligation. Here, the authors present a Cryo-EM structure of the human 4-subunit Pol δ bound to DNA and PCNA in a replicating state with an incoming nucleotide in the active site.

Food extract's biological effect and its improvement using nanotechnologies is one of the challenges of the last and the future decades; for this reason, the antioxidant effect of scarlet eggplant extract liposomal incorporation was investigated. Scarlet eggplant (

Rotondas Red Eggplant belongs to the family of Solanum aethiopicum species, cultivated in a specific area of Potenza (Basilicata, Italy) and has gained the Protected Designation of Origin certification. Recently, Red Eggplant was associated with different biological properties, related to health benefits, as antioxidant, hypoglycemic, antihypertensive and hypolipidemic, probably due to its chemical composition. The search for "greener" technologies has been one of the focus of research, having in mind industrial applications. In this sense, electrotechnologies, such as ohmic heating (OH), have been explored, showing to have potentially lower energy costs, higher extraction yields, being less time consuming and increasing the biocompounds chemical stability. The aim of this study was to determine the chemical/nutritional composition of Red Eggplant and to assess conventional and OH methods in the extraction and recovery of the main bio-compounds present in this material. Red Eggplant was characterized for the nutritional profile (AOAC procedures): proteins, carbohydrates, total extractives, lipids, ash and minerals. The selected conditions for the extraction of the main biocompounds, for conventional and OH methods, were: solid/liquid ratio 1:10 (w:v), 80 °C, 25 min and water or mixture of 50% (v/v) ethanol/water as a solvent. Subsequently, assays were carried out to determine the content of proteins (Bradford), total carbohydrates (phenolsulfuric acid) and phenolics (Folin-Ciocalteu), and antioxidant activity (FRAP and DPPH) of the obtained extracts. Monosaccharides profile after hydrolysis and phenolics were also quantified by HPLC. Results showed that carbohydrates were the major macronutrient, followed by protein, lipids and ash. K, Ca and Mg were the major minerals. Regarding the monosaccharide composition, glucose, fructose, xylose and arabinose were the most abundant sugars. Ethanolic extractives represented approximately 46 % of the Red Eggplant composition. Independently of the solvent, higher amounts of polyphenols, proteins and carbohydrates were extracted when OH was applied. Moreover, OH extracts showed greater antioxidant activity compared to extracts obtained by the conventional extraction method. According to the polyphenol profile of the extracts the main compounds found were taxifolin, rutin and rosmarinic acid. These results demonstrate the potential of this vegetable to be used for nutraceuticals or functional food., The authors wish to thank for the financial support to funding program Marie Skłodowska-Curie grant (MSCA-RISE; FODIAC; 778388). Pedro Santos is recipient of a fellowship supported by a doctoral advanced training (call NORTE-69-2015-15), funded by the European Social Fund under the scope of Norte2020 - Programa Operacional Regional do Norte (NORTE-08-5369-FSE-000036). Zlatina Genisheva is supported by the project OH2O (POCI-01-0145-FEDER-029145) funded by FCT and Fundo Europeu de Desenvolvimento Regional (FEDER) under the scope of Programa Operacional de Competividade e Internacionalizaçao (POCI)-COMPETE 2020 and Portugal 2020., info:eu-repo/semantics/publishedVersion

The relationship between satellite-derived absolute sea level change rates, tide gauge (TG) observations of relative sea level change and global positioning system (GPS) measurements of vertical land motion (VLM) at local scale has been investigated in previous studies [eg. Vignudelli et al., 2018]. The paucity of collocated TG-GPS data and the lack of a well-established mathematical frame in which simultaneous and optimal solutions can be derived, have emphasized the difficulty of deriving spatially-consistent information on the sea level rates. Other studies have claimed the possibility to set locally isolated information into a coherent regional framework using a constrained linear inverse problem approach [Kuo et al., 2004; Wöppelmann and Marcos, 2012].The approach cited in the above papers has been recently improved in De Biasio et al. [2020]. A step in advance is now to develop an effective synergistic use of global positioning system (GPS) data, tide gauge measurements and satellite altimetry observations. In this study GPS data are used as a real source of information on the relative Vertical Land Motion (VLM) between pairs of tide gauges, and not as mere term of comparison of the results obtained by differencing relative and absolute sea level observations time series.Long, consistent and collocated tide gauge and GPS observations time series are extracted for a handful of suitable coastal locations, and used in the original formulation of the constrained linear inverse problem, together with satellite altimetry data. Some experiments are conducted without GPS observations (traditional setup), and with GPS observations (the new proposed approach) Results are compared in order to assess the impact of GPS observations directly into the formulation of the constrained linear inverse problem.The satellite altimetry data-set used in this study is that offered by the European Copernicus Climate Change Service (C3S) through its Climate Data Store archive. It covers the global ocean since 1993 to present, with spatial resolution of 0.25 x 0.25 degrees. This data set is constantly updated and relies only on a couple of simultaneous altimetry missions at a time to provide stable long-term variability estimates of sea level. Tide gauge data are extracted from the Permanent Service for Mean Sea Level archive and from other local sea level monitoring services. GPS vertical position time series and/or VLM rates are taken from the Nevada Geodetic Laboratory and other public GPS repositories.REFERENCESVignudelli, S.; De Biasio, F.; Scozzari, A.; Zecchetto, S.; Papa, A. In Proceedings of the International Association of Geodesy Symposia; Mertikas, S.P., Pail, R., Eds.; Springer: Cham, Switzerland, 2020; Volume 150, pp. 65–74. DOI: 10.1007/1345_2018_51Kuo, C.Y.; Shum, C.K.; Braun, A.; Mitrovica, J.X. Geophys. Res. Lett. 2004, 31. DOI: 10.1029/2003GL019106Wöppelmann, G.; Marcos, M. J. Geophys. Res. Ocean. 2012, 117. DOI: 10.1029/2011JC007469De Biasio, F.; Baldin, G.; Vignudelli, S. J. Mar. Sci. Eng. 2020, 8, 949. DOI: 10.3390/jmse8110949

During lagging strand synthesis, DNA Ligase 1 (Lig1) cooperates with the sliding clamp PCNA to seal the nicks between Okazaki fragments generated by Flap endonuclease 1 (FEN1), but the structural basis of this mechanism is unknown. We present cryo-EM structures of human Lig1 bound to nicked DNA and PCNA in absence and presence of FEN1. Lig1 and PCNA form a two-ring complex encircling the DNA substrate. The ligase DNA binding domain (DBD) dynamically tethers Lig1 to one PCNA protomer, leaving one protomer fully accessible for FEN1 engagement. Ligation assays argue that Lig1 binding to PCNA is critical for substrate handoff from FEN1 preassembled with nicked DNA and PCNA. Consistently, cryo-EM data show that when Lig1 and FEN1 are simultaneously bound to one PCNA ring, the nicked DNA is trapped within the ligase active site and poised for the end-joining reaction. Thus, PCNA functions as a bivalent platform for the synchronous coordination of Lig1 and FEN1 in Okazaki fragment sealing.

In the Adriatic Sea, the sea surface wind forecasts are often underestimated, with detrimental effects on the accuracy of sea level and storm surge predictions. Among the various causes, this mainly depends on the meteorological forcing of the wind. In this paper, we try to improve an existing numerical method, called “wind bias mitigation”, which relies on scatterometer wind observations to determine a multiplicative factor Δw, whose application to the model wind reduces its inaccuracy with respect to the scatterometer wind. Following four different mathematical approaches, we formulate and discuss seven new expressions of the multiplicative factor. The eight different expressions of the bias mitigation factor, the original one and the seven formulated in this study, are assessed with the aid of four datasets of real sea surface wind events in a variety of sea level conditions in the northern Adriatic Sea, several of which gave rise to high water events in the Venice Lagoon. The statistical analysis shows that some of the seven new formulations of the wind bias mitigation factor are able to lower the model-scatterometer bias with respect to the original formulation. For some other of the seven new formulations, the absolute bias, with respect to scatterometer, of the mitigated model wind field, results lower than that supplied by the unmodified model wind field in 81% of the considered storm surge events in the area of interest, against the 73% of the original formulation of the wind bias mitigation. This represents an 11% improvement in the bias mitigation process, with respect to the original formulation. The best performing of the seven new wind bias mitigation factors, that based on the linear least square regression of the squared wind speed (LLSRE), has been implemented in the operational sea level forecast chain of the Tide Forecast and Early Warning Centre of the Venice Municipality (CPSM), to provide support to the operation of the MO.SE. barriers in Venice.

Coastal altimetry is an important observational resource for a better understanding of coastal oceanographic processes and their dynamic connection between the inland and open ocean. During the last decade significant improvements have been achieved in using satellite radar altimetry near coasts. Advances in processing and new/improved corrections permitted to obtain accurate sea level estimations within few kilometers from the coast. The retrieval of waves and winds in the coastal zone is as yet not as mature as sea level measurements. The advent of SAR altimetry now permits to achieve higher spatial resolution and better precision than before. However, there is a need to assess the quality and the accuracy of these new data sets in order to gain the proper confidence in their operational usage. HYDROCOASTAL, a project funded by ESA, aims at maximizing exploitation of SAR measurements in the coastal zone and inland waters, by evaluating and implementing new approaches to process SAR data from the CryoSat-2 Sentinel-3 European satellites. The Northern Adriatic Sea and the area around Venice is a perfect site to test modern altimetry applied to coastal studies in virtue of the favourable location of altimetric tracks as well as the availability of long-term in-situ observations from a number of instruments including tide gauges, wave and wind recorders, that offer clear advantages for comparison purposes. The aim of this work is the presentation of comparison results of CryoSat-2 and Sentinel-3 data processed with GPOD, in preparation of exploiting HYDROCOASTAL re-processed datasets of sea level, wave amplitude and wind speed in support of regional monitoring.

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fsufs.2021.804004/full#supplementary-material, Eggplants contain a multitude of biocompounds with nutritional and/or biological activities. The objective of this work was to study the nutritional, chemical and bioactive value of red eggplant from Rotonda, Italy. Ohmic heating (OH) was compared to conventional heating, as different solvents were used (water, ethanol 30, 50, and 90% and methanol) for biocompounds extraction. Extracts were evaluated for their total phenolic compounds, antioxidant and antibacterial activities, and its toxicity was assessed in cells, L929 and Caco-2. The nutritional characterization of Rotonda's eggplant demonstrated that it is rich in carbohydrates (65%), fiber (12.5%), proteins (13%), lipids (7.6%) and minerals. Potassium is the mineral with the highest concentration in the red eggplant (27.24 mg/g). Phenolic composition of the obtained extracts was dependent on the extraction method, as well as on the solvent. The use of OH method increased the extraction of biocompounds, especially when using 50% of ethanol as solvent. The main phenolic compounds found in the extracts of this eggplant variety were ellagic acid, p-coumaricic acid, epicatechin, narginin, taxifolin and kaempferol. Antioxidant activity was positively correlated with the total amounts of phenolics. Red Eggplant extracts showed activity against Gram-negative bacteria (E. coli and S. enterica), however, they did not demonstrate activity against Gram-positive bacteria. The extracts obtained did not show cytotoxic effects in fibroblast and colorectal studied cells. Ohmic heating is a sustainable technology that increases the extraction yield of biocompounds, with reduced energy consumption and the resulting extracts show low toxicity and high biological activity. Copyright © 2021 Ferreira-Santos, Duca, Genisheva, Silva, De Biasio, Botelho, Rocha, Gorgoglione and Teixeira., This research was funded by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and by program Marie Skłodowska-Curie grant (MSCA-RISE; FODIAC; 778388)., info:eu-repo/semantics/publishedVersion