Search

The present investigation explores the spatial distribution of Cooper pair density in graph-shaped arrays of Josephson junctions using a Ginzburg–Landau approach. We specifically investigate double-comb structures and compare their properties with linear arrays as reference systems. Our findings reveal that the peculiar connectivity of the double-comb structure leads to spatial gradients in the order parameter, which can be readily detected through measurements of Josephson critical currents. We present experimental results which indicate the specific dependence of the order parameter on the branches of the graphs and are evidence of the theoretical predictions.

Summary: Replication origin assembly is a pivotal step in chromosomal DNA replication. In this process, the ORC complex binds DNA and, together with the CDC6 and CDT1, promotes the loading of the MCM helicase. Chemicals targeting origin assembly might be useful to sensitize highly proliferative cancer cells. However, identifying such compounds is challenging due to the multistage nature of this process. Here, using Xenopus laevis egg extract we set up a high-throughput screening to isolate MCM chromatin loading inhibitors, which led to the identification of NSC-95397 as a powerful inhibitor of replication origin assembly that targets CDC6 protein and promotes its degradation. Using systems developed to test selective drug-induced lethality we show that NSC-95397 triggers cell death both in human cells and Xenopus embryos that have higher proliferative ability. These findings demonstrate the effectiveness of molecules disrupting DNA replication processes in targeting hyperproliferating cells, highlighting their potential as anti-cancer molecules.

Abstract The production of heavy neutral mass resonances, $$\text {Z}^{\prime }$$ Z ′ , has been widely studied theoretically and experimentally. Although the nature, mass, couplings, and associated quantum numbers of this hypothetical particle are yet to be determined, current LHC experimental results have set strong constraints assuming the simplest beyond Standard Model (SM) hypotheses. We present a new feasibility study on the production of a $$\text {Z}^{\prime }$$ Z ′ boson at the LHC, with family non-universal couplings, considering proton–proton collisions at $$\sqrt{s} = 13$$ s = 13 and 14 TeV. Such a hypothesis is well motivated theoretically and it can explain observed differences between SM predictions and experimental results, as well as being a useful tool to further probe recent results in searches for new physics considering non-universal fermion couplings. We work under two simplified phenomenological frameworks where the $$\textrm{Z}^{\prime }$$ Z ′ masses and couplings to the SM particles are free parameters, and consider final states of the $$\text {Z}^{\prime }$$ Z ′ decaying to a pair of $$\textrm{b}$$ b quarks. The analysis is performed using machine learning techniques to maximize the sensitivity. Despite being a well motivated physics case in its own merit, such scenarios have not been fully considered in ongoing searches at the LHC. We note the proposed search methodology can be a key mode for discovery over a large mass range, including low masses, traditionally considered difficult due to experimental constrains. In addition, the proposed search is complementary to existing strategies.

On 21 May 2023, a hidden eruption occurred at the Southeast Crater (SEC) of Etna (Italy); indeed, bad weather prevented its direct and remote observation. Tephra fell toward the southwest, and two lava flows propagated along the SEC’s southern and eastern flanks. The monitoring system of the Istituto Nazionale di Geofisica e Vulcanologia testified to its occurrence. We analyzed the seismic and infrasound signals to constrain the temporal evolution of the fountain, which lasted about 5 h. We finally reached Etna’s summit two weeks later and found an unexpected pyroclastic density current (PDC) deposit covering the southern lava flow at its middle portion. We performed unoccupied aerial system and field surveys to reconstruct in 3D the SEC, lava flows, and PDC deposits and to collect some samples. The data allowed for detailed mapping, quantification, and characterization of the products. The resulting lava flows and PDC deposit volumes were (1.54 ± 0.47) × 106 m3 and (1.30 ± 0.26) × 105 m3, respectively. We also analyzed ground-radar and satellite data to evaluate that the plume height ranges between 10 and 15 km. This work is a comprehensive analysis of the fieldwork, UAS, volcanic tremor, infrasound, radar, and satellite data. Our results increase awareness of the volcanic activity and potential dangers for visitors to Etna’s summit area.

Background: The COVID-19 pandemic and its impact on hospitals' activity and organization has imposed a vast change in standard neurosurgical oncology practice to accommodate for shifting resources. Aims: This investigation aims to analyse the nationwide capability in reorganizing the surgical neuro-oncological activity during the COVID-19 pandemic to evaluate whether COVID-19-pandemic influenced the surgical management in these patients. Method: A web-based dataset model organized by the Italian Neurosurgical Society (SINCh) was sent to all the Italian neurosurgical departments in May 2021, requesting to report the types and numbers of surgical procedures performed in the pre-pandemic period (from March 9th 2019 to March 9th 2020) compared to the pandemic period (from March 10th 2020 to March 10th 2021). Results: This multicentre investigation included the surgical activity of 35 Italian Neurosurgical Departments in a pre-pandemic year versus a pandemic year. During the COVID period, 699 fewer neuro-oncological patients were operated on than in the pre-COVID period. We noted a slight increase in urgency and a more severe decrease in elective and benign pathology. None of these differences was statistically significant. Surgically treated patients who tested positive for SARS-CoV-2 were 36, of which 11 died. Death was found to be COVID-related only in 2 cases. Conclusion: The reorganization of the Italian Neurosurgical Departments was able to guarantee a redistribution of the CNS tumors during the inter-pandemic periods, demonstrating that patients even in the pandemic era could be treated without compromising the efficacy and safety of the surgical procedure.

Topological electronics is an emerging field aiming at exploiting the topological properties of matter in devices with extended functionalities. Recent experiments demonstrate a topological current divider, a key circuit element for this emerging technology.

This review describes the relationship between the coronavirus-related pandemic and health inequities. The latter are linked to pre-existing social and economic discriminations in terms of access to healthcare for people affected by chronic diseases. We believe that we are living in a “syndemic pandemic”. The term “syndemic” was originally developed by the medical anthropologist Merrill Singer in the 1990s in order to recognize the correlation between HIV/AIDS, illicit drug use, and violence in the United States. This complex interplay exacerbated the burden of the disease and the prognosis of the patient. Similarly, in COVID-19 infection, socio-economic, ethnic, and racial inequities result in higher morbidity and mortality in certain sections of society. Unfortunately, such differences are becoming too common during the COVID-19 pandemic, in terms of the incidence and prevalence of the disease, as well as inequal access to new medical advances and life-saving therapeutics for those with COVID-19, such as vaccines and monoclonal antibody treatment. Lockdown measures, imposed internationally as a response to the COVID-19 pandemic, are causing economic inequities, which complicate the issue even further. An appropriate syndemic anthropological approach is necessary to ensure that this pandemic does not increase health inequities in access to appropriate treatments.

Summary: Combined inhibition of oxidative phosphorylation (OXPHOS) and glycolysis has been shown to activate a PP2A-dependent signaling pathway, leading to tumor cell death. Here, we analyze highly selective mitochondrial complex I or III inhibitors in vitro and in vivo to elucidate the molecular mechanisms leading to cell death following OXPHOS inhibition. We show that IACS-010759 treatment (complex I inhibitor) induces a reactive oxygen species (ROS)-dependent dissociation of CIP2A from PP2A, leading to its destabilization and degradation through chaperone-mediated autophagy. Mitochondrial complex III inhibition has analogous effects. We establish that activation of the PP2A holoenzyme containing B56δ regulatory subunit selectively mediates tumor cell death, while the arrest in proliferation that is observed upon IACS-010759 treatment does not depend on the PP2A-B56δ complex. These studies provide a molecular characterization of the events subsequent to the alteration of critical bioenergetic pathways and help to refine clinical studies aimed to exploit metabolic vulnerabilities of tumor cells.

Atherosclerosis is a chronic inflammatory disease characterized by lipid and inflammatory cell deposits in the inner layer of large- and medium-sized elastic and muscular arteries. Diabetes mellitus (DM) significantly increases the risk of cardiovascular diseases and the overall and cardiovascular mortality, and it is a pro-atherogenic factor that induces atherosclerosis development and/or accelerates its progression through a multifactorial process. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of drugs, belonging to the armamentarium to fight type 2 DM, that have shown robust reductions in atherosclerotic events and all-cause mortality in all studies. Preclinical studies have shown that GLP-1RAs play a role in the immunomodulation of atherosclerosis, affecting multiple pathways involved in plaque development and progression. In this review, we wanted to explore the translational power of such preclinical studies by analyzing the most recent clinical trials investigating the atheroprotective effect of GLP-1RAs.

Abstract Aims Chronic heart failure with reduced ejection fraction remains a major health issue. To date, no reliable biomarker is available to predict reduced left ventricular ejection fraction (LV‐EF). We aimed to identify novel circulating biomarkers for reduced left ventricular function using untargeted serum metabolomics in two independent patient cohorts. Methods and results Echocardiography and non‐targeted serum metabolomics were conducted in two patient cohorts with varying left ventricular function: (1) 25 patients with type 2 diabetes with established cardiovascular disease or high cardiovascular risk (LV‐EF range 20–66%) (discovery cohort) and (2) 37 patients hospitalized for myocardial infarction (LV‐EF range 25–60%) (validation cohort). In the discovery cohort, untargeted metabolomics revealed seven metabolites performing better than N‐terminal pro‐B‐type natriuretic peptide in the prediction of impaired left ventricular function shown by LV‐EF. For only one of the metabolites, acisoga, the predictive value for LV‐EF could be confirmed in the validation cohort (r = −0.37, P = 0.02). In the discovery cohort, acisoga did not only correlate with LV‐EF (r = −60, P = 0.0016), but also with global circumferential strain (r = 0.67, P = 0.0003) and global longitudinal strain (r = 0.68, P = 0.0002). Similar results could be detected in the discovery cohort in a 6 month follow‐up proofing stability of these results over time. With an area under the curve of 0.86 in the receiver operating characteristic analysis, acisoga discriminated between patients with normal EF and LV‐EF

Understanding the pathophysiology of atherosclerosis is fundamental to the practice of cardiovascular medicine. Atherosclerosis is a multi-step cascade of accumulation of lipids and downstream changes that lead to a fibro-fatty plaque formation in the arterial intima. Multiple biochemical stimuli, cellular receptors and intra-cellular signals are implicated in this complex mechanism. Lectin-type oxidized LDL receptor-1 or LOX-1 is a type II membrane glycoprotein receptor which has emerged as an important effector of atherosclerosis. Hence, LOX-1 modification and its clinical consequences are of much interest in recent times.

In this paper, we describe a rare case of coronary artery aneurysms occasionally found on a pre interventional Coronary Computed Tomography Angiography performed on a 67-year-old man with a history of aneurysm of the ascending aorta previously treated with Bentall surgery, who arrived at our hospital to have a percutaneous valve-in-valve implantation procedure. Even though the patient was considered not eligible for the procedure, due to his many comorbidities, and conservatively managed, at 1-year followup his angiographic condition remained stable.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting 32 million individuals worldwide, particularly the elderly. It is the main cause of ischemic strokes. Oral anticoagulation (OAC) is the gold standard strategy for stroke prevention. Still, there is a not negligible share of patients who have contraindications to this therapy, more frequently due to an increased risk of bleeding. AF is often associated with moderate-severe mitral regurgitation (MR), the second most frequent valvular disease in elderly patients. Data from the literature reported that more than half of patients with severe mitral regurgitation are not suitable candidates for cardiac surgery. Given the progressive aging of the population and the simultaneous increase in the number of patients with comorbidities, the advent of new therapeutic strategies, such as the combined approach of Left Atrial Appendage Occlusion (LAAO) and MitraClip procedure, is acquiring great interest. At present, the category of patients who may benefit from combined percutaneous therapies and the long-term risks and benefits might not have been identified. Despite the efforts of researchers, the correct selection of patients is a very important clinical need that has not yet been met to avoid committing human and financial resources to interventions that may be unnecessary. It is conceivable that the most modern and recent innovations in cardiovascular imaging, particularly three-dimensional echocardiography and new methods of volume imaging, could improve our ability to select patients appropriately. Since data in the literature are scarce, future studies will be needed to evaluate the efficacy and safety of combined MitraClip and LAA occlusion.

Background Patients affected by the human immunodeficiency virus (HIV) show an increased risk of myocardial infarction. Clinical and angiographic features of HIV positive (HIV+) patients presenting with the first episode of an acute coronary syndrome (ACS) are not well defined in previous studies. Objective To demonstrate that HIV + patients with acute coronary syndrome had different features than non-HIV patients. Methods We identified 48 HIV + patients without previous cardiovascular events admitted to our Emergency Department with ACS diagnosis between 2012 and 2020. Clinical and angiographic characteristics were compared with a control group of 48 non-HIV consecutive patients affected by ACS as first episode. Results HIV + patients were most frequently men (87.5% vs 62.5%, p = 0.009) and younger about a decade (mean age 53.8 ± 8.2 vs 63.7 ± 11.9 years old, p

Valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) is emerging as an effective treatment for patients with symptomatically failing bioprosthetic valves and a high prohibitive surgical risk; a longer life expectancy has led to a higher demand for these valve reinterventions due to the increased possibilities of outliving the bioprosthetic valve’s durability. Coronary obstruction is the most feared complication of valve-in-valve (ViV) TAVR; it is a rare but life-threatening complication and occurs most frequently at the left coronary artery ostium. Accurate pre-procedural planning, mainly based on cardiac computed tomography, is crucial to determining the feasibility of a ViV TAVR and to assessing the anticipated risk of a coronary obstruction and the eventual need for coronary protection measures. Intraprocedurally, the aortic root and a selective coronary angiography are useful for evaluating the anatomic relationship between the aortic valve and coronary ostia; transesophageal echocardiographic real-time monitoring of the coronary flow with a color Doppler and pulsed-wave Doppler is a valuable tool that allows for a determination of real-time coronary patency and the detection of asymptomatic coronary obstructions. Because of the risk of developing a delayed coronary obstruction, the close postprocedural monitoring of patients at a high risk of developing coronary obstructions is advisable. CT simulations of ViV TAVR, 3D printing models, and fusion imaging represent the future directions that may help provide a personalized lifetime strategy and tailored approach for each patient, potentially minimizing complications and improving outcomes.

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007.

During embryonic development, it is vital to maintain rapid genome duplication. Here, the authors shed light on the mechanism by revealing that SSRP1 stimulates replication origin assembly on somatic nuclei in Xenopus laevis egg extract by promoting histone H1 eviction from somatic chromatin.

A tight binding supercell approach is used for the calculation of the electronic structure of the (111) LaAlO3/SrTiO3 interface. The confinement potential at the interface is evaluated solving a discrete Poisson equation by means of an iterative method. In addition to the effect of the confinement, local Hubbard electron–electron terms are included at the mean-field level within a fully self-consistent procedure. The calculation carefully describes how the two-dimensional electron gas arises from the quantum confinement of electrons near the interface due to the band bending potential. The resulting electronic sub-bands and Fermi surfaces show full agreement with the electronic structure determined by angle-resolved photoelectron spectroscopy experiments. In particular, we analyse how the effect of local Hubbard interactions change the density distribution over the layers from the interface to the bulk. Interestingly, the two-dimensional electron gas at the interface is not depleted by local Hubbard interactions which indeed induce an enhancement of the electron density between the first layers and the bulk.

Satellite microwave (MW) and millimetre-wave (MMW) passive sensors can be used to detect volcanic clouds because of their sensitivity to larger volcanic particles (i.e., size bigger than 20 µm). In this work, we combine the MW-MMW observations with thermal-infrared (TIR) radiometric data from the Low Earth Orbit (LEO) spectroradiometer to have a complete characterisation of volcanic plumes. We describe new physical-statistical methods, which combine machine learning techniques, aimed at detecting and retrieving volcanic clouds of two highly explosive eruptions: the 2014 Kelud and 2015 Calbuco test cases. For the detection procedure, we compare the well-known split-window methods with a machine learning algorithm named random forest (RF). Our work highlights how the machine learning method is suitable to detect volcanic clouds using different spectral signatures without fixing a threshold. Moreover, the RF model allows images to be automatically processed with promising results (90% of the area correctly identified). For the retrieval procedure of the mass of volcanic particles, we consider two methods, one based on the maximum likelihood estimation (MLE) and one using the neural network (NN) architecture. Results show a good comparison of the mass obtained using the MLE and NN methods for all the analysed bands. Summing the MW-MMW and TIR estimates, we obtain the following masses: 1.11 ± 0.40 × 1011 kg (MLE method) and 1.32 ± 0.47 × 1011 kg (NN method) for Kelud; 4.48 ± 1.61 × 1010 kg (MLE method) and 4.32 ± 1.56 × 1010 kg (NN method) for Calbuco. This work shows how machine learning techniques can be an effective tool for volcanic cloud detection and how the synergic use of the TIR and MW-MMW observations can give more accurate estimates of the near-source volcanic clouds.

Measurements indicating that planar networks of superconductive islands connected by Josephson junctions display long-range quantum coherence are reported. The networks consist of superconducting islands connected by Josephson junctions and have a tree-like topological structure containing no loops. Enhancements of superconductive gaps over specific branches of the networks and sharp increases in pair currents are the main signatures of the coherent states. In order to unambiguously attribute the observed effects to branches being embedded in the networks, comparisons with geometrically equivalent—but isolated—counterparts are reported. Tuning the Josephson coupling energy by an external magnetic field generates increases in the Josephson currents, along the above-mentioned specific branches, which follow a functional dependence typical of phase transitions. Results are presented for double comb and star geometry networks, and in both cases, the observed effects provide positive quantitative evidence of the predictions of existing theoretical models.

Abstract Background Rheumatic heart disease (RHD) is a chronic condition responsible of congestive heart failure, stroke and arrhythmia. Almost eradicated in high-income countries (HIC), it persists in low- and middle-income countries. The purpose of the study was to assess the feasibility and meaningfulness of ultrasound-based RHD screening among the population of unaccompanied foreign minors in Italy and determine the burden of asymptomatic RHD among this discrete population. Methods From February 2016 to January 2018, Médecins Sans Frontières conducted a weekly mobile screening by echocardiography in reception centers and family houses for unaccompanied foreign minors in Rome, followed by fix echocardiographic retesting for those resulting positive at screening. ‘Definite’ and ‘borderline’ cases were defined according to the World Hearth Federation criteria. Results Six hundred fifty-three individuals (13–26 years old) were screened; 95.6% were below 18 years old (624/653). Six ‘definite RHD’ were identified at screening, yielding a detection rate of 9.2‰ (95% CI 4.1–20.3‰), while 285 (436.4‰) were defined as ‘borderline’ (95% CI 398.8–474.9‰). Out of 172 “non-negative borderline” cases available for being retested (113 “non-negative borderline” lost in follow-up), additional 11 were categorized as ‘definite RHD’, for a total of 17 ‘definite RHD’, yielding a final prevalence of 26.0‰ (95% CI 16.2–41.5‰) (17/653), and 122 (122/653) were confirmed as ‘borderline’ (final prevalence of 186.8‰, 95% CI 158.7–218.7). In multivariate logistic regression analysis the presence of systolic murmur was a strong predictor for both ‘borderline’ (OR 4.3 [2.8–6.5]) and ‘definite RHD’ (OR 5.2 [1.7–15.2]), while no specific country/geographic area of origin was statistically associated with an increased risk of latent, asymptomatic RHD. Conclusions Screening for RHD among the unaccompanied migrant minors in Italy proved to be feasible. The burden of ‘definite RHD’ was similar to that identified in resource-poor settings, while the prevalence of ‘borderline’ cases was higher than reported in other studies. In view of these findings, the health system of high-income countries, hosting migrants and asylum seekers, are urged to adopt screening for RHD in particular among the silent and marginalized population of refugee and migrant children.

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia and associated with an increased risk of morbidity and mortality, primarily from cardiovascular and renal diseases. Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) are novel drugs for the treatment of type 2 DM and heart failure (HF). SGLT2-Is mediate protective effects on both the renal and cardiovascular systems. This review addresses the current knowledge on the biomolecular mechanisms of the cardiorenal protective effects of SGLT2-Is, which appear to act mainly through non-glucose-mediated pathways. Cardiorenal protection mechanisms lead to reduced chronic renal disease progression and improved myocardial and coronary endothelial function. Concomitantly, it is possible to observe reflected changes in biomarkers linked with diabetic kidney disease and HF.

Converting charge current into spin current is one of the main mechanisms exploited in spintronics. One prominent example is the Edelstein effect, namely, the generation of a magnetization in response to an external electric field, which can be realized in systems with lack of inversion symmetry. If a system has electrons with an orbital angular momentum character, an orbital magnetization can be generated by the applied electric field, giving rise to the so-called orbital Edelstein effect. Oxide heterostructures are the ideal platform for these effects due to the strong spin–orbit coupling and the lack of inversion symmetries. Beyond a gate-tunable spin Edelstein effect, we predict an orbital Edelstein effect an order of magnitude larger then the spin one at the (111) LaAlO3/SrTiO3 interface for very low and high fillings. We model the material as a bilayer of t2g orbitals using a tight-binding approach, whereas transport properties are obtained in the Boltzmann approach. We give an effective model at low filling, which explains the non-trivial behaviour of the Edelstein response, showing that the hybridization between the electronic bands crucially impacts the Edelstein susceptibility.

Background: Recent studies have shown that patients diagnosed with coronarivus disease 2019 (COVID-19) and also with previous cardiovascular diseases have a higher mortality due to worsening heart disease. At the same time, patients without previous cardiovascular disease may also have cardiac complications. The aim of this multicenter study was to assess high sensitivity cardiac troponin T (hs-cTnT) in patients with COVID-19 and to evaluate the incidence of myocardial injury. Methods: In this multicenter study we enrolled 543 patients, 57.8% males, median age 63 years (range 18–99) from three selected hospitals: University Hospital Tor Vergata in Rome, Fondazione IRCCS Ca 'Granda Ospedale Maggiore Policlinico, in Milan, S Chiara Hospital in Trento. We measured hs-cTnT in all patients to assess myocardial injury and correlations with patient’s age, symptoms and disease course. Results: The data showed that, among the 543 patients studied, 257 patients (47.3%) had hs-cTnT values higher than the upper reference limit (URL) of 14 ng/L. Patients with high hs-cTnT had more frequently fever (p

Background After the coronavirus disease 2019 outbreak, social isolation measures were introduced to contain infection. Although there is currently a slowing down of the infection, a reduction of hospitalizations, especially for myocardial infarction, was observed. The aim of our study is to evaluate the impact of the infectious disease on ST‐segment–elevation myocardial infarction (STEMI) care during the coronavirus disease 2019 pandemic, through the analysis of recent cases of patients who underwent percutaneous coronary intervention. Methods and Results Consecutive patients affected by STEMI from March 1 to 31, 2020, during social restrictions of Italian government, were collected and compared with patients with STEMI treated during March 2019. During March 2020, we observed a 63% reduction of patients with STEMI who were admitted to our catheterization laboratory, when compared with the same period of 2019 (13 versus 35 patients). Changes in all time components of STEMI care were notably observed, particularly for longer median time in symptom‐to‐first medical contact, spoke‐to‐hub, and the cumulative symptom‐to‐wire delay. Procedural data and in‐hospital outcomes were similar between the 2 groups, whereas the length of hospitalization was longer in patients of 2020. In this group, we also observed higher levels of cardiac biomarkers and a worse left ventricular ejection fraction at baseline and discharge. Conclusions The coronavirus disease 2019 outbreak induced a reduction of hospital access for STEMI with an increase in treatment delay, longer hospitalization, higher levels of cardiac biomarkers, and worse left ventricular function.

We grew Sr1-xLaxCuO2 thin films and SrCuO2/Sr0.9La0.1CuO2/SrCuO2 trilayers by reflection high-energy diffraction-calibrated layer-by-layer molecular beam epitaxy, to study their electrical transport properties as a function of the doping and thickness of the central Sr0.9La0.1CuO2 layer. For the trilayer samples, as already observed in underdoped SLCO films, the electrical resistivity versus temperature curves as a function of the central layer thickness show, for thicknesses thinner than 20 unit cells, sudden upturns in the low temperature range with the possibility for identifying, in the normal state, the T* and a T** temperatures, respectively, separating high-temperature linear behavior and low-temperature quadratic dependence. By plotting the T* and T** values as a function of TConset for both the thin films and the trilayers, the data fall on the same curves. This result suggests that, for the investigated trilayers, the superconducting critical temperature is the important parameter able to describe the normal state properties and that, in the limit of very thin central layers, such properties are mainly influenced by the modification of the energy band structure and not by interface-related disorder.

Background: To retrospectively evaluate the difference in terms of pathologic complete response (pCR) according to time elapsed between chemoradiation (CRT) and total mesorectal excision (TME) on a large unselected real-life dataset of locally advanced rectal cancer (LARC) patients. Methods: A multicentre retrospective cohort study of LARC patients from 21 Italian Radiotherapy Institutions was performed. Patients were stratified into 3 different time intervals from CRT. The 1st group included 300 patients who underwent TME within 6 weeks, the 2nd 1598 patients (TME within 7–12 weeks) and the 3rd 196 patients (TME within 13 or more weeks after CRT), respectively. Results: Data on 2094 LARC patients treated between 1997 and 2016 were considered suitable for analysis. Overall, 578 patients had stage II while 1516 had stage III histological proven invasive rectal adenocarcinoma. A CRT schedule of one agent (N = 1585) or 2-drugs (N = 509) was administered. Overall, pCR was 22.3% (N = 468 patients). The proportion of patients achieving pCR with respect to time interval was, as follows: 12.6% (1st group), 23% (2nd group) and 31.1% (3rd group) (p 5040 cGy (p = 0.002) and longer interval (p 13 weeks) from CRT to surgery improves the pathological response (pCR and pathologic partial response; pPR) in comparison to historic data. Furthermore, radiotherapy dose >5040 cGy and two drugs chemotherapy correlated with pPR rate.

Endocarditis due to Lactobacillus species is extremely rare. We report an uncommon case of Lactobacillus plantarum bioprosthetic aortic valve endocarditis, presenting with severe aortic steno-regurgitation, which responded to conventional medical and surgical treatment. This case provides a better understanding of the disease process of L. plantarum and highlights the role of transesophageal echocardiography in following the entire course of endocarditis.

A 49-year-old man with malignant hypertension had been admitted with hemorrhagic stroke. Refractory hypertension had been observed during hospitalization and the decision had been made to perform renal denervation. A significant blood pressure reduction was obtained immediately after renal denervation and persists at 2-year follow-up. This case demonstrates the long-term sustained efficacy of renal denervation performed in the acute phase of hemorrhagic stroke. In addition, it supports the notion that renal denervation–induced normalization of blood pressure may contribute to better outcomes in a challenging setting such as intracranial bleeding.

Background Current literature only reports variable information from single‐center studies on the recurrence rate, the complications, and the outcome of patients with Takotsubo syndrome (TTS) experiencing recurrent TTS. Therefore, a detailed description of clinical characteristics, predictors, and the prognostic impact of patients with TTS and recurrences in a multicenter registry is needed. Methods and Results We analyzed 749 patients with TTS from 9 European centers being part of the international, multicenter GEIST (German Italian Stress Cardiomyopathy) Registry. Patients were divided into the recurrence group and the nonrecurrence group. The recurrence rate at a median follow‐up of 830 days (interquartile range, 118–1701 days) was 4%. Most recurrences were documented in the first 5 years after the index TTS episode. Up to 2 TTS recurrences were documented in 2 of 30 patients (6%). A variable ballooning pattern (n=6, 0.8%) with, in particular, involvement of the right ventricular occurred in 3 cases (0.4%) at the recurrence event. Except for the higher presence of arterial hypertension (86.7% versus 68.3%; P=0.03) in the recurrence group, no other baseline characteristics were different between groups. Observation of TTS complications during follow‐up, including stroke, thromboembolic events, in‐hospital death, and cardiogenic shock, revealed no significant differences between groups (P>0.05), except the higher presence of pulmonary edema in the recurrence group versus the nonrecurrence group (13.3% versus 4.9%; P=0.04). Conclusions The incidence of TTS recurrence is estimated to be 4% in this multicenter TTS registry. A variable TTS pattern at recurrence is common in up to 20% of recurrence cases.

Coronary artery disease (CAD) and acute myocardial infarction (AMI) are the leading causes of death worldwide. Since only a subset of CAD patients develops myocardial infarction, it is likely that unique factors predispose to AMI. Circulating microRNAs represent diagnostic powerful biomarkers for detection of heart injuries and patients' risk stratification. Using an array-based approach, the expression of 84 circulating miRNAs was analyzed in plasma of pooled stable CAD patients (CAD; n = 5) and unstable CAD patients (AMI_T0; n = 5) enrolled within 24 hours from an AMI event. The array experiments showed 27 miRNAs differentially expressed with a two-fold up- or down-regulation (10 up- and 17 down-regulated miRNAs). Among them, miR-423-5p dis-regulation was confirmed in a larger case study (n = 99). Circulating miR-423-5p resulted to be significantly down-regulated within 24 hours from the AMI event (FC = -2, p≤0.05). Interestingly, miR-423-5p expression resulted to be increased (FC = +2; p≤0.005) in a subgroup of the same AMI patients (AMI_T1; n = 11) analyzed after 6 months from the acute event. We extended miR-423-5p expression study on PBMCs (peripheral blood mononuclear cells), confirming also in this tissue its up-regulation at 6 months post-AMI. Receiver operating characteristic analyses (ROC) were performed to detect the power of miR-423-5p to discriminate stable and unstable CAD. In plasma, miR-423-5p expression accurately distinguishes stable and unstable CAD patients (AUC = 0.7143, p≤0.005). Interestingly, the highest discriminatory value (AUC = 0.8529 p≤0.0005) was identified in blood cells, where miR-423-5p expression is able to differentiate unstable CAD patients during an acute event (AMI_T0) from those at six months post-AMI (AMI_T1). Furthermore, cellular miR-423-5p may discriminate also stable CAD patients from unstable CAD patients after six months post-AMI (AUC = 0.7355 p≤0.05). The results of this pilot-study suggest that miR-423-5p expression level both in plasma and blood cells, could represent a new promising biomarker for risk stratification of CAD patients.

In this work, the general problem of the characterization of the topological phase of an open quantum system is addressed. In particular, we study the topological properties of Kitaev chains and ladders under the perturbing effect of a current flux injected into the system using an external normal lead and derived from it via a superconducting electrode. After discussing the topological phase diagram of the isolated systems, using a scattering technique within the Bogoliubov−de Gennes formulation, we analyze the differential conductance properties of these topological devices as a function of all relevant model parameters. The relevant problem of implementing local spectroscopic measurements to characterize topological systems is also addressed by studying the system electrical response as a function of the position and the distance of the normal electrode (tip). The results show how the signatures of topological order affect the electrical response of the analyzed systems, a subset of which being robust also against the effects of a moderate amount of disorder. The analysis of the internal modes of the nanodevices demonstrates that topological protection can be lost when quantum states of an initially isolated topological system are hybridized with those of the external reservoirs. The conclusions of this work could be useful in understanding the topological phases of nanowire-based mesoscopic devices.

We studied the effects of low-energy electron beam irradiation up to 10 keV on graphene-based field effect transistors. We fabricated metallic bilayer electrodes to contact mono- and bi-layer graphene flakes on SiO2, obtaining specific contact resistivity ρ c ≈ 19 k Ω · µ m 2 and carrier mobility as high as 4000 cm2·V−1·s−1. By using a highly doped p-Si/SiO2 substrate as the back gate, we analyzed the transport properties of the device and the dependence on the pressure and on the electron bombardment. We demonstrate herein that low energy irradiation is detrimental to the transistor current capability, resulting in an increase in contact resistance and a reduction in carrier mobility, even at electron doses as low as 30 e−/nm2. We also show that irradiated devices recover their pristine state after few repeated electrical measurements.

Background and purposeThe lectin-like oxidised LDL receptor-1 (OLR1) gene encodes a scavenger receptor implicated in the pathogenesis of atherosclerosis. Although functional roles have been suggested for two variants, epidemiological studies on OLR1 have been inconsistent.MethodsWe tested the association between the non-synonymous substitution K167N (rs11053646) and intima media thickness of the common carotid artery (CCA-IMT) in 2,141 samples from the Progression of Lesions in the Intima of the Carotid (PLIC) study (a prospective population-based study).ResultsSignificantly increased IMT was observed in male carriers of the minor C (N) allele compared to GC and GG (KN and KK) genotype. Functional analysis on macrophages suggested a decreased association to Ox-LDL in NN carriers compared to KN and KK carriers which is also associated with a reduced OLR1 mRNA expression. Macrophages from NN carriers present also a specific inflammatory gene expression pattern compared to cells from KN and KK carriers.ConclusionsThese data suggest that the 167N variant of LOX-1 receptor affects the atherogenic process in the carotid artery prior to evidence of disease through an inflammatory process.

Oxidized LDL (ox-LDL) is a key factor in atherogenesis. It is taken up by endothelial cells primarily by ox-LDL receptor-1 (LOX-1). To elucidate transcriptional responses, we performed microarray analysis on human coronary artery endothelial cells (HCAECs) exposed to small physiologic concentration of ox-LDL- 5 µg/ml for 2 and 12 hours. At 12 hours, cultures treated with ox-LDL exhibited broad shifts in transcriptional activity involving almost 1500 genes (>1.5 fold difference, p

No previous reports are available about the potential dramatic effects resulting from the combination of acquired long QT interval not associated to bradycardia and myocardial ischemia. We report the case of a man that during acute necrotic pancreatitis presented QT interval prolongation without bradycardia, TdP, and two episodes of cardiac arrest. A coronary angiogram revealed a subocclusive stenosis of left anterior descending coronary artery, treated with a percutaneous coronary intervention. After myocardial revascularization, even in presence of long QT interval, no arrhythmic events occurred suggesting the key role of myocardial ischemia in triggering TdP in acquired long QT even without bradycardia. ECG performed six months later, after complete recovery from pancreatitis, showed a normal QT interval.

Atrial fibrillation is a common clinical disease especially in the elderly and in patients with organic heart disease. Electrical cardioversion is the first choice therapeutic approach for patients in which sinus rhythm could improve the quality of life and where the maintenance of sinus rhythm is considered likely. There are different techniques to perform an electrical cardioversion, each with specific indications, advantages, and limitations. The method most frequently used to restore sinus rhythm is external direct current cardioversion; however, this technique has some disadvantages, since it requires a high energy and usually general anesthesia. Esophageal cardioversion is an alternative method to obtain restoration of sinus rhythm, warranting acute and long-term results absolutely comparable with those obtained by the conventional transthoracic technique, especially in obese and COPD patients with high thoracic impedance for whom the standard technique may be less effective.

The human lectin-like oxidized low density lipoprotein receptor 1 LOX-1, encoded by the ORL1 gene, is the major scavenger receptor for oxidized low density lipoprotein in endothelial cells. Here we report on the functional effects of a coding SNP, c.501G>C, which produces a single amino acid change (K>N at codon 167). Our study was aimed at elucidating whether the c.501G>C polymorphism changes the binding affinity of LOX-1 receptor altering its function. The presence of p.K167N mutation reduces ox-LDL binding and uptake. Ox-LDL activated extracellular signal-regulated kinases 1 and 2 (ERK 1/2) is inhibited. Furthermore, ox-LDL induced biosynthesis of LOX-1 receptors is dependent on the p.K167N variation. In human macrophages, derived from c.501G>C heterozygous individuals, the ox-LDL induced LOX-1 46 kDa band is markedly lower than in induced macrophages derived from c.501G>C controls. Investigation of p.K167N mutation through molecular dynamics simulation and electrostatic analysis suggests that the ox-LDL binding may be attributed to the coupling between the electrostatic potential distribution and the asymmetric flexibility of the basic spine residues. The N/N-LOX-1 mutant has either interrupted electrostatic potential and asymmetric fluctuations of the basic spine arginines.