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Defining the molecular mechanisms underlying cardiac resilience is crucial to find effective approaches to protect the heart. A physiologic level of ROS is produced in the heart by fatty acid oxidation, but stressful events can boost ROS and cause mitochondrial dysfunction and cardiac functional impairment. Melusin is a muscle specific chaperone required for myocardial compensatory remodeling during stress. Here we report that Melusin localizes in mitochondria where it binds the mitochondrial trifunctional protein, a key enzyme in fatty acid oxidation, and decreases it activity. Studying both mice and human induced pluripotent stem cell-derived cardiomyocytes, we found that Melusin reduces lipid oxidation in the myocardium and limits ROS generation in steady state and during pressure overload and doxorubicin treatment, preventing mitochondrial dysfunction. Accordingly, the treatment with the lipid oxidation inhibitor Trimetazidine concomitantly with stressful stimuli limits ROS accumulation and prevents long-term heart dysfunction. These findings disclose a physiologic mechanism of metabolic regulation in the heart and demonstrate that a timely restriction of lipid metabolism represents a potential therapeutic strategy to improve cardiac resilience to stress. Synopsis: FAO is catalyzed by the mitochondrial trifunctional protein (MTP) and, if overloaded, generates ROS. ROS are boosted during stressful events, favoring cardiac maladaptive remodeling. Melusin is a muscle-specific chaperone able to sustain heart resilience during a wide variety of stressful insults. Melusin interacts and inhibits the MTP, restraining FAO and ROS generation in the myocardium. Heart resilience depends on the rate of FAO during stressful events occurrence. Inhibiting lipid metabolism in a timely manner during stress protects the heart from dysfunction and prolongs the survival in preclinical models. FAO is catalyzed by the mitochondrial trifunctional protein (MTP) and, if overloaded, generates ROS. ROS are boosted during stressful events, favoring cardiac maladaptive remodeling. Melusin is a muscle-specific chaperone able to sustain heart resilience during a wide variety of stressful insults. [ABSTRACT FROM AUTHOR]

Ischemia/reperfusion injury is attracting continuous interest in science for two reasons: because it affects several clinical conditions and because it has been identified, albeit in broad terms, the molecular entity becoming activated by the reperfusion damage paradoxes. Indeed, calcium, oxygen‐dependent oxidative stress and pH would activate conformational changes in the mitochondrial cristae embedded F1/FO ATP synthase, allowing the formation of pores in the inner mitochondrial membrane thus increasing its permeability. This is a key determinant for mitochondrial stress, cell death and tissue dysfunction. Targeting each of these factors has never contributed to improved clinical outcome of the patients affected by reperfusion damage; now, the focus on the PTP opening could represent the closest target to solve this pathway made by extensive cell death when the tissues become revascularized. In this review, we summarized last knowledge about the structure, the modulation and the therapeutic targeting of the PTP, focusing on ATP synthase and cardiac ischemia/reperfusion. [ABSTRACT FROM AUTHOR]

Introduction: Thermal atrial fibrillation (AF) ablation exerts an additive treatment effect on the cardiac autonomic nervous system (CANS). This effect is mainly reported during ablation of the right superior pulmonary vein (RSPV), modulating the right anterior ganglionated plexus (RAGP), which contains parasympathetic innervation to the sinoatrial node in the epicardial fat pad between RSPV and superior vena cava (SVC). However, a variable response to neuromodulation after ablation is observed, with little to no effect in some patients. Our objective was to assess clinical and anatomic predictors of thermal ablation‐induced CANS changes, as assessed via variations in heart rate (HR) postablation. Methods: Consecutive paroxysmal AF patients undergoing first‐time PV isolation by the cryoballoon (CB) or radiofrequency balloon (RFB) within a 12‐month time frame and with preprocedural cardiac computed tomography (CT), were evaluated. Preablation and 24‐h postablation electrocardiograms in sinus rhythm were collected and analyzed to assess HR. Anatomic evaluation by CT included the measurement of the shortest distance between the SVC and RSPV ostium (RSPV‐SVC distance). Results: A total of 97 patients (CB, n = 50 vs. RFB, n = 47) were included, with similar baseline characteristics between both groups. A significant HR increase postablation (ΔHR ≥ 15 bpm) occurred in a total of 37 patients (38.1%), without difference in number of patients between both thermal ablation technologies (CB, 19 [51%]), RFB, 18 [49%]). Independent predictors for increased HR were RSPV‐SVC distance (odds ratio [OR]: 0.49, CI: 0.34–0.71, p value <.001), and age (OR: 0.94, CI: 0.89–0.98, p value =.003). Conclusions: Thermal balloon‐based PV isolation influences the CANS through its effect on the RAGP, especially in younger patients and patients with shorter RSPV‐SVC distance. [ABSTRACT FROM AUTHOR]

Two model substrates for the grafting to reaction are considered: not‐deglazed silicon, whose surface is coated by a thin oxide layer with reactive silanol groups on its surface; and deglazed silicon, where the oxide layer is removed by treatment with hydrofluoric acid. The reactive polymers are hydroxy‐terminated polystyrenes with molecular weights ranging from 3.9 to 13.9 kg mol⁻1. The grafting to reaction is carried out at different temperatures and for different periods of time on the two different substrates. The thickness and the thermal stability of the resulting brushes are evaluated. Furthermore, the grafting of a highly dispersed system is simulated by blending two polymers with different molecular weights. Although the brush thickness growth is found to be faster on deglazed silicon, the preferential grafting of short chains occurs with equal chain selection propensity on both substrates. [ABSTRACT FROM AUTHOR]

In the past, several wild plants were widely consumed as food by humans. Dandelion [Taraxacum officinale (L.) Weber ex F.H. Wigg] is a wild species with remarkable nutritional and medicinal properties. Many studies have investigated the chemical components of the plant for human health. Nonetheless, little research has been carried out on the cultivation and related production of this species. With this study, we intend to investigate some cultural practices to start defining an efficient protocol for dandelion cultivation in northern Italy. Two seeding rates (0.14 and 0.55 g m−2) and two harvest regimes (when leaves reached a length of 20 cm and 1 week later) were compared. Leaf fresh weight yield was determined at each harvest, and the following morphological parameters were measured: plant height, number of plants per square meter, number of leaves per square meter, leaf area index, number of leaves per plant, leaf weight, and specific leaf weight. The productivity of dandelion was found to be unaffected by the seeding rate, and no significant differences were found between harvest regimes. The delayed harvest regime was only advantageous at the first cut as it allowed for a longer establishment phase, resulting in a higher yield. The nitrate content in the leaves differed between the first two cuts and the third and fourth cuts with both harvest regimes and both sowing rates. Core Ideas: Dandelion is a wild species that can be intensively cultivated for human nutrition.Two seeding rates and two harvest regimes were tested over four cuts during the dandelion growing period.Seeding rate and harvest regime affected dandelion leaf yield and nitrate content.Dandelion annual productivity was unaffected by the seeding rate and harvest regimes.Nitrate content was affected by the interaction between harvest regime, cut, and seeding rate. [ABSTRACT FROM AUTHOR]

Background: It is reported that treatment with anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) induces hypogonadism both in male patients with ALK‐positive cancer and in murine models. Methods: In this study, three groups, including an experimental group of male patients with ALK‐positive, advanced non–small cell lung cancer (ANSCLC) who were receiving alectinib (cohort A), a control group of female patients with ALK‐positive ANSCLC who were receiving alectinib (cohort B), and a control group of male patients with ALK‐negative ANSCLC (cohort C), prospectively underwent a full hormone assessment for androgen deficiency at 8 weeks after the start of treatment and in case of reported suspected symptoms. Patients with major sexual dysfunctions were referred to an endocrinologist. Results: Ninety‐five patients were consecutively enrolled onto the study. Among sixty‐eight male patients, both median total testosterone levels (2.93 vs. 4.92 ng/ml; p =.0001) and free testosterone levels (0.11 vs. 0.17 pg/ml; p =.0002) were significantly lower in ALK‐positive ANSCLC patients in cohort A compared with ALK‐negative patients in cohort C; conversely, median FSH (10.32 vs. 17.52 mUI/ml; p =.0059) and LH levels (4.72 vs. 7.49 mUI/ml; p =.0131) were significantly higher in cohort C compared to cohort A. Median inhibin B levels were higher in ALK‐positive male patients (74.3 vs. 44.24 pg/ml; p =.0038), but all patients had inhibin B values within the normal range. The percentage of male patients who had positive scores on the Androgen Deficiency in Aging Males (ADAM) questionnaire was 62% in cohort A and 26.8% in cohort C, including eight patients who reported at least one major symptom and were referred to Andrology Unit. No significant differences in the endocrine assessment were reported between cohorts A and B. Conclusions: Symptoms of androgen deficiency should be tracked in male patients with ALK‐positive ANSCLC who are receiving alectinib, and testosterone replacement should be considered, as appropriate. Male patients with ALK‐positive advanced non–small cell lung cancer treated with first‐line alectinib had lower median total testosterone (p =.0001) and free testosterone (p =.0002) levels compared with male patients who had ALK‐negative disease and were receiving other anticancer treatments. Symptoms of hypogonadism were more frequent in ALK‐positive patients compared with ALK‐negative patients (62% vs 26.8% rates of positive score at ADAM questionnaire, respectively), suggesting the need for hormone assessment and referral to an andrologist, as appropriate. [ABSTRACT FROM AUTHOR]

Background: The limited therapies available for treating Merkel cell carcinoma (MCC), a highly aggressive skin neoplasm, still pose clinical challenges, and novel treatments are required. Targeting retinoid signalling with retinoids, such as all‐trans retinoic acid (ATRA), is a promising and clinically useful antitumor approach. ATRA drives tumour cell differentiation by modulating retinoid signalling, leading to anti‐proliferative and pro‐apoptotic effects. Although retinoid signalling is dysregulated in MCC, ATRA activity in this tumour is unknown. This study aimed to evaluate the impact of ATRA on the pathological phenotype of MCC cells. Methods: The effect of ATRA was tested in various Merkel cell polyomavirus‐positive and polyomavirus‐negative MCC cell lines in terms of cell proliferation, viability, migration and clonogenic abilities. In addition, cell cycle, apoptosis/cell death and the retinoid gene signature were evaluated upon ATRA treatments. Results: ATRA efficiently impaired MCC cell proliferation and viability in MCC cells. A strong effect in reducing cell migration and clonogenicity was determined in ATRA‐treated cells. Moreover, ATRA resulted as strongly effective in arresting cell cycle and inducing apoptosis/cell death in all tested MCC cells. Enrichment analyses indicated that ATRA was effective in modulating the retinoid gene signature in MCC cells to promote cell differentiation pathways, which led to anti‐proliferative and pro‐apoptotic/cell death effects. Conclusions: These results underline the potential of retinoid‐based therapy for MCC management and might open the way to novel experimental approaches with other retinoids and/or combinatorial treatments. [ABSTRACT FROM AUTHOR]

Attaining precise control over molecular arrangements is of paramount importance for numerous applications in nanotechnology, particularly in constructing molecular templates to accurately immobilize target materials on surfaces. A strategic combination of supramolecular and interfacial chemistry may serve to build a well‐organized molecular network, enabling the subsequent location of target molecules on specific positions of a surface. A supramolecular complex (compound 1) comprised of a melamine unit forming hydrogen bonds with dendritic arms terminated in a coumarin unit is utilized, which readily undergoes photodimerization. The research demonstrates the formation of well‐organized Langmuir films of compound 1 which can be transferred on substrates at low surface pressures adopting a lying‐flat orientation. Upon irradiation of the pristine films at 365 nm the coumarin units undergo photo‐cross linking, leading to the formation of a compact photo‐crosslinked film. Incubation of these photo‐crosslinked films in a solution containing 1‐hexanethiol results in the withdrawal of the melamine and the chemisorption of two thiol molecules per each melamine unit. The nanopores created by the removal of the melamine core are attributed to the disruption of hydrogen bonds in compound 1 by the thiols. This precisely defined molecular network holds significant promise as a template for orchestrating the arrangement of functional materials on surfaces. [ABSTRACT FROM AUTHOR]

This systematic review investigates the diagnostic and prognostic utility of coronary flow reserve (CFR) assessment through echocardiography in patients with left bundle branch block (LBBB), a condition known to complicate the clinical evaluation of coronary artery disease (CAD). The literature search was performed on PubMed, EMBASE, Web of Science, Scopus, and Google Scholar, was guided by PRISMA standards up to March 2024, and yielded six observational studies that met inclusion criteria. These studies involved a diverse population of patients with LBBB, employing echocardiographic protocols to clarify the impact of LBBB on coronary flow dynamics. The findings emphasize the importance of CFR in stratifying cardiovascular risk and guiding clinical decision‐making in patients with LBBB. Pooled results reveal that patients with LBBB and significant left anterior descending (LAD) artery stenosis exhibited a marked decrease in stress‐peak diastolic velocity (MD = ‐19.03 [‐23.58; ‐14.48] cm/s; p <.0001) and CFR (MD = ‐.60 [‐.71; ‐.50]; p <.0001), compared to those without significant LAD lesions, suggesting the efficacy of stress echocardiography CFR assessment in the identification of clinically significant CAD among the LBBB population. This review highlights the clinical relevance of echocardiography CFR assessment as a noninvasive tool for evaluating CAD and stratifying risk in the presence of LBBB and underscores the need for standardized protocols in CFR measurement. [ABSTRACT FROM AUTHOR]

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GrafeoPlad‐Pd, a new metal‐organic alloy comprised of Pd nanoparticles doped with 3D‐entrapped graphene oxide, has promising applicative potential in sustainable synthetic organic chemistry. Besides hydrogenation, the metal nanopowder comprising the material is also active and relatively stable in cross‐coupling reactions carried out consecutively. X‐ray photoelectron spectroscopy (XPS) surface investigation and density functional theory (DFT) calculations are applied to gain new insight into the structure and potential new catalytic activity of this new class of molecularly doped metals. [ABSTRACT FROM AUTHOR]

Nowadays, the great diffusion of the Internet of Things and the improvements in Artificial Intelligence techniques have given a rise in the development and application of data‐driven approaches for Predictive Maintenance to reduce the costs linked to the maintenance of industrial machinery. Due to the wide real‐life applications and the strong interest by even more industries, this field is highly attractive for academics and practitioners. So, constructing efficient frameworks to address the Predictive Maintenance problem is an open debate. In this work, we propose a Deep Learning approach for the feature extraction in the offshore oil wells monitoring context, exploiting the public 3 W dataset, which is well‐known in the literature. The dataset is made up of about 2000 multivariate time series labelled according to the corresponding functioning of the well. So, there is a classification task with eight classes, each related to a particular machinery condition. Thanks to the peculiarities of the labels, the proposed framework is valid both for diagnostics and prognostics. In more detail, we compare two different approaches in feature extraction. The first is a statistical approach, widely used in the literature related to the considered dataset; the second is based on Convolutional 1D AutoEncoder. The extracted features are then used as input for several Machine Learning algorithms, namely the Random Forest, Nearest Neighbours, Gaussian Naive Bayes and Quadratic Discriminant Analysis. Different experiments on various time horizons prove the worthiness of the Convolutional AutoEncoder. [ABSTRACT FROM AUTHOR]

Introduction: Mitral valve prolapse (MVP) is a common clinical condition in the general population. A subgroup of patients with MVP may experience ventricular arrhythmias and sudden cardiac death ("arrhythmic mitral valve prolapse" [AMVP]) but how to stratify arrhythmic risk is still unclear. Our meta‐analysis aims to identify predictive factors for arrhythmic risk in patients with MVP. Methods: We systematically searched Medline, Cochrane, Journals@Ovid, Scopus electronic databases for studies published up to December 28, 2022 and comparing AMVP and nonarrhythmic mitral valve prolapse (NAMVP) for what concerns history, electrocardiographic, echocardiographic and cardiac magnetic resonance features. The effect size was estimated using a random‐effect model as odds ratio (OR) and mean difference (MD). Results: A total of 10 studies enrolling 1715 patients were included. Late gadolinium enhancement (LGE) (OR: 16.67; p =.005), T‐wave inversion (TWI) (OR: 2.63; p <.0001), bileaflet MVP (OR: 1.92; p <.0001) and mitral anulus disjunction (MAD) (OR: 2.60; p <.0001) were more represented among patients with AMVP than in NAMVP. Patients with AMVP were shown to have longer anterior mitral leaflet (AML) (MD: 2.63 mm; p <.0001), posterior mitral leaflet (MD: 2.96 mm; p <.0001), thicker AML (MD: 0.49 mm; p <.0001), longer MAD length (MD: 1.24 mm; p <.0001) and higher amount of LGE (MD: 1.41%; p <.0001) than NAMVP. AMVP showed increased mechanical dispersion (MD: 8.04 ms; 95% confidence interval: 5.13–10.96; p <.0001) compared with NAMVP. Conclusions: Our meta‐analysis proved that LGE, TWI, bileaflet MVP, and MAD are predictive factors for arrhythmic risk in MVP patients. [ABSTRACT FROM AUTHOR]

Daylight photoluminescence (DPL) is a relatively novel imaging technique utilized in photovoltaic (PV) system inspection, using the sun as excitation source. Filtering the luminescence signal from the strong sun irradiation is its main challenge. Images acquired at two different operating points (OPs) of the module, allow subtraction of the background radiation while maintaining the luminescence signal. A DPL‐ready inverter, which is able to toggle between manually selectable OPs of connected PV modules, is presented in this work. Synchronization of image acquisition and OP switching becomes particularly challenging if the camera is applied to unmanned aerial vehicles. To overcome this challenge, an algorithm is developed to identify OP switches in a set of images taken in the field by investigating image intensities. Further, by working out the detailed dependencies of the signal recorded during DPL, the temperature coefficient of photoluminescence intensity is derived theoretically, and its impact on quantitative inspections. The potential field application of DPL images to identify performance loss in PV modules is investigated by two approaches: recording the signal intensity of images over time and comparing the signal intensity of different PV modules in one image. For both approaches, their hypothetical applicability is shown experimentally. [ABSTRACT FROM AUTHOR]

Background: High‐power‐short‐duration (HPSD) radiofrequency (RF) ablation is a viable alternative to low‐power‐long‐duration (LPLD) RF for pulmonary vein isolation (PVI). Nevertheless, trials showed conflicting results regarding atrial fibrillation (AF) recurrences and few data concerning complications. Therefore, we conducted a meta‐analysis of randomized trials comparing HPSD versus LPLD. Methods: We systematically searched the electronic databases for studies published from inception to March 31, 2023 focusing on HPSD versus LPLD. The study endpoints were AF recurrence, procedural times and overall complications. Results: Five studies enrolling 424 patients met the inclusion criteria (mean age 61.1 years; 54.3% paroxysmal AF; mean LVEF 58.2%). Compared to LPLD, HPSD showed a significantly lower AF recurrence rate [16.3% vs. 30,1%; RR: 0.54 (95% CI: 0.38–0.79); p = 0.001] at a mean 10.9 months follow‐up. Moreover, HPSD led to a significant reduction in total procedural time [MD: −26.25 min (95%CI: −42.89 to −9.61); p = 0.002], PVI time [MD: −26.44 min (95%CI: −38.32 to −14.55); p < 0.0001], RF application time [MD: −8.69 min (95%CI: −11.37 to −6.01); p < 0.00001] and RF lesion number [MD: −7.60 (95%CI: −10.15 to −5.05); p < 0.00001]. No difference was found in either right [80.4% vs. 78.2%; RR: 1.04 (95% CI: 0.81–1.32); p = 0.77] or left [92.3% vs. 90.2%; RR: 1.02 (95% CI: 0.94–1.11); p = 0.58] first‐pass isolation and overall complications [6% vs. 3.7%; RR: 1.45 (95%CI: 0.53–3.99); p = 0.47] between groups. Conclusion: In our metanalysis of randomized trials, HPSD ablation appeared to be associated to a significantly improved freedom from AF and shorter procedures, without increasing the risk of complications. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary vein isolation (PVI) with thermal energy is characterized by concomitant ablation of the surrounding ganglionated plexi (GP). Pulsed‐field ablation (PFA) selectively targets the myocardium and seems associated with only negligible effects on the autonomic nervous system (ANS). However, little is known about the dynamic effects of PFA on the GP immediately after PVI. This study sought to investigate the degree and acute vagal modulation induced by the FarapulseTM PFA system during PVI compared with single‐shot thermal ablation. Methods: A total of 76 patients underwent first‐time PVI with either FarapulseTM PFA (PFA group, n = 40) or cryoballoon ablation (thermal ablation group, n = 36) for paroxysmal atrial fibrillation (AF). The effect on the ANS in the two groups was assessed before and after PVI with extracardiac vagal stimulation (ECVS). To capture any transient effects of PFA on the ANS, in a subgroup of PFA patients ECVS was repeated at three predefined timepoints: (1) before PVI (T0); (2) immediately after PVI (T1); and (3) 10 min after the last energy application (T2). Results: Despite similar baseline values, the vagal response induced by ECVS after PVI almost disappeared in the thermal ablation group but persisted in the PFA group (thermal group: 840 [706–1090] ms, p <.001 compared to baseline; PFA group: 11 466 [8720–12 293] ms, p =.70 compared to baseline). Intraprocedural vagal reactions (defined as RR increase >50%, transitory asystole, or atrioventricular block) occurred more frequently with PFA than thermal ablation (70% vs. 28%, p =.001). Moreover, heart rate 24 h post‐PVI increased more with thermal ablation than with PFA (16.5 ± 9.0 vs. 2.6 ± 6.1 beats/min, p <.001). In the subgroup of PFA patients undergoing repeated ANS modulation assessment (n = 11), ECVS demonstrated that PFA determined a significant acute suppression of the vagal response immediately after PVI (p <.001 compared to baseline), which recovered almost completely within 10 min. Conclusion: PVI with the FarapulseTM PFA system is associated with only transitory and short‐lasting vagal effects on the ANS which recover almost completely within a few minutes after ablation. The impact of this phenomenon on AF outcome needs to be further investigated. [ABSTRACT FROM AUTHOR]

This study investigated the effectiveness of regulatory interventions in mitigating the harmful effects of financial crises on small firms. We examine the impact of a support factor implemented by European policymakers on Italian micro‐, small‐, and medium‐sized enterprises (MSMEs) between 2007 and 2017. The analysis uses a difference‐in‐differences approach to assess the credit conditions of these firms. Contrary to expectations, our results show that MSMEs in Italy continue to face credit constraints even after the introduction of the support factor. In contrast, we find that structural factors and portfolio effects play a more important role in promoting favorable credit conditions for small firms. Our results highlight the importance of considering these factors in conjunction with regulatory interventions to achieve better outcomes. This study has implications for policymakers and stakeholders, particularly in assessing the appropriateness of extending support factors for different policy purposes. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease is a prevalent condition in surgical patients. Possible associations with increased postoperative morbidity and mortality have not been clearly demonstrated in patients undergoing pancreatoduodenectomy. The aim of this study was to assess the risk of postoperative complications in patients with reduced kidney function undergoing pancreatoduodenectomy. Methods: All patients undergoing pancreatoduodenectomy at Karolinska University Hospital between 2008 and 2019 were retrospectively included. The variable of interest was chronic kidney disease, based on preoperative estimated glomerular filtration rate measurements. Unadjusted and adjusted logistic regression analyses were performed for standardized postoperative complications. Results: A total of 971 patients were included in the study, of whom 92 (10%) had an estimated glomerular filtration rate < 60 mL/min/1.73m2, equivalent to chronic kidney disease Stage 3a or worse. Patients with chronic kidney disease had a higher odds of longer hospital stay (adjusted odds ratio 1.58, 95% confidence interval 1.00–2.50) and postoperative weight increase (adjusted odds ratio 2.02, 1.14–3.56). A 10 unit increase of preoperative estimated glomerular filtration rate was associated to lower odds of intensive care unit admission (adjusted odds ratio 0.81, 0.69–0.95), delayed gastric emptying (adjusted odds ratio 0.90, 0.81–0.99), and post‐operative pancreatic fistula (adjusted odds ratio 0.83, 0.74–0.94). Conclusion: Patients undergoing pancreatoduodenectomy with decreased preoperative kidney function are more likely to experience major postoperative complications, and also postoperative weight increase. Preoperative kidney function assessment is important in risk stratification before pancreatoduodenectomies. [ABSTRACT FROM AUTHOR]

Sub‐nanometer metal clusters have special physical and chemical properties, significantly different from those of nanoparticles. However, there is a major concern about their thermal stability and susceptibility to oxidation. In situ X‐ray Absorption spectroscopy and Near Ambient Pressure X‐ray Photoelectron spectroscopy results reveal that supported Cu5 clusters are resistant to irreversible oxidation at least up to 773 K, even in the presence of 0.15 mbar of oxygen. These experimental findings can be formally described by a theoretical model which combines dispersion‐corrected DFT and first principles thermochemistry revealing that most of the adsorbed O2 molecules are transformed into superoxo and peroxo species by an interplay of collective charge transfer within the network of Cu atoms and large amplitude "breathing" motions. A chemical phase diagram for Cu oxidation states of the Cu5‐oxygen system is presented, clearly different from the already known bulk and nano‐structured chemistry of Cu. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac involvement is common and may become clinically relevant in approximately 5%–10% of patients with systemic sarcoidosis. Although reduced left ventricular ejection fraction is a recognized predictor of mortality, recent studies have suggested an increased risk of ventricular arrhythmia (VAs) and sudden cardiac death (SCD) in patients with cardiac sarcoidosis (CS) and evidence of late gadolinium enhancement‐cardiac magnetic resonance (LGE‐CMR), irrespective of the underlying left ventricular systolic function. We performed a meta‐analysis to assess the correlation between VAs/SCD and presence of LGE‐CMR in CS patients. Methods: We systematically searched Medline, Embase, and Cochrane electronic databases up to January 2, 2023, for studies enrolling patients with suspected or confirmed CS undergoing LGE‐CMR. Clinical outcomes of interest included clinically relevant VAs, defined as sustained ventricular tachycardia, ventricular fibrillation, SCD, or aborted SCD during follow‐up. The effect size was estimated using a random‐effect model as risk ratio (RR) and relative 95% confidence interval (CI). Results: A total of 14 studies fulfilled the selection criteria and were included in the final analysis. Among 1273 patients, LGE was detected in 465 (36.5%; Group LGE+). Males accounted for 45.2% (95% CI: 40.5%–55.7%) of the total population and the average age was 56.8 (95% CI: 52.7%–60.9) years. A total of 104 (22.3%) of 465 LGE+ patients experienced a clinically relevant VA, compared to 6 (0.7%) of 808 LGE‐ ones. LGE+ was associated with a ninefold increased risk in life‐threatening VAs (22.3% vs. 0.7%; RR = 9.52; 95% CI [5.18–17.49]; p <.0001) compared to patients without LGE (heterogeneity I2 = 0%). Conclusion: In our meta‐analysis, LGE+ in patients with CS was associated with a ninefold increased risk in life‐threatening VAs compared to patients without LGE. [ABSTRACT FROM AUTHOR]

Introduction: Cephalic vein cutdown (CVC) and axillary vein puncture (AVP) are both recommended for transvenous implantation of leads for cardiac implantable electronic devices (CIEDs). Nonetheless, it is still debated which of the two techniques has a better safety and efficacy profile. Methods: We systematically searched Medline, Embase, and Cochrane electronic databases up to September 5, 2022, for studies that evaluated the efficacy and safety of AVP and CVC reporting at least one clinical outcome of interest. The primary endpoints were acute procedural success and overall complications. The effect size was estimated using a random‐effect model as risk ratio (RR) and relative 95% confidence interval (CI). Results: Overall, seven studies were included, which enrolled 1771 and 3067 transvenous leads (65.6% [n = 1162] males, average age 73.4 ± 14.3 years). Compared to CVC, AVP showed a significant increase in the primary endpoint (95.7 % vs. 76.1 %; RR: 1.24; 95% CI: 1.09–1.40; p =.001) (Figure 1). Total procedural time (mean difference [MD]: −8.25 min; 95% CI: −10.23 to −6.27; p <.0001; I2 = 0%) and venous access time (MD: −6.24 min; 95% CI: −7.01 to −5.47; p <.0001; I2 = 0%) were significantly shorter with AVP compared to CVC. No differences were found between AVP and CVC for incidence overall complications (RR: 0.56; 95% CI: 0.28–1.10; p =.09), pneumothorax (RR: 0.72; 95% CI: 0.13−4.0; p =.71), lead failure (RR: 0.58; 95% CI: 0.23–1.48; p =.26), pocket hematoma/bleeding (RR: 0.58; 95% CI: 0.15–2.23; p =.43), device infection (RR: 0.95; 95% CI: 0.14–6.60; p =.96) and fluoroscopy time (MD: −0.24 min; 95% CI: −0.75 to 0.28; p =.36). Conclusion: Our meta‐analysis suggests that AVP may improve procedural success and reduce total procedural time and venous access time compared to CVC. [ABSTRACT FROM AUTHOR]

Background and purpose: Although two doses of COVID‐19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease‐modifying therapies (DMTs) showed less efficient responses. Methods: This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS. Results: Four hundred seventy‐three pwMS were analyzed. Compared to untreated patients, there was a 50‐fold decrease (95% confidence interval [CI] = 14.3–100.0, p < 0.001) in serum SARS‐CoV‐2 antibody levels in those on rituximab, a 20‐fold decrease (95% CI = 8.3–50.0, p < 0.001) in those on ocrelizumab, and a 2.3‐fold decrease (95% CI = 1.2–4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti‐CD20 drugs rituximab and ocrelizumab showed a 2.3‐fold lower gain (95% CI = 1.4–3.8, p = 0.001), whereas those on fingolimod showed a 1.7‐fold higher gain (95% CI = 1.1–2.7, p = 0.012), compared to patients treated with other DMTs. Conclusions: All pwMS increased their serum SARS‐CoV‐2 antibody levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical "protective threshold" for risk of infection identified in the CovaXiMS study (>659 binding antibody units/mL), whereas for patients treated with fingolimod this value was significantly closer to the cutoff. [ABSTRACT FROM AUTHOR]

The handling of yield‐stress fluids typically involves a jammed‐to‐flow transition that is pivotal for many injection and transport technologies on different scales, such as additive manufacturing, injection molding, food rheology, and oil transport. For all of these applications, it is crucial to be able to tune the fluidization under constant load. The pressure‐driven flow of emulsions is reported within a microfluidic channel, one wall of which is patterned by a herringbone‐riblet roughness comprising a regular array of V‐shaped grooves. With respect to the pressure gradient, this pattern displays a convergent (divergent) orientation that provides a forward (backward) direction. At the tip of the herringbone pattern, the forward and backward flows are almost identical for a viscous Newtonian fluid and a diluted emulsion, whereas a surprising flow boost in the forward direction is observed as the emulsion approaches a jammed state. The flow boost is more effective at small herringbone angles and low pressure loads. 3D velocity profiles along the channel cross‐section unravel unexpected heterogeneous stress, band‐like distributed, with evidence of nonlocal correlations. [ABSTRACT FROM AUTHOR]

Animal models of human brain disorders permit researchers to explore disease mechanisms and to test potential therapies. However, therapeutic molecules derived from animal models often translate poorly to the clinic. Although human data may be more relevant, experiments on patients are constrained, and living tissue is unavailable for many disorders. Here, we compare work on animal models and on human tissue for three epileptic syndromes where human tissue is excised therapeutically: (1) acquired temporal lobe epilepsies, (2) inherited epilepsies associated with cortical malformations, and (3) peritumoral epilepsies. Animal models rest on assumed equivalencies between human brains and brains of mice, the most frequently used model animal. We ask how differences between mouse and human brains could influence models. General principles and compromises in model construction and validation are examined for a range of neurological diseases. Models may be judged on how well they predict novel therapeutic molecules or new mechanisms. The efficacy and safety of new molecules are evaluated in clinical trials. We judge new mechanisms by comparing data from work on animal models with data from work on patient tissue. In conclusion, we stress the need to cross‐verify findings from animal models and from living human tissue to avoid the assumption that mechanisms are identical. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac resynchronization therapy (CRT) reduces heart failure (HF) hospitalization and all‐cause mortality in HF patients with left bundle branch block (LBBB). Biventricular pacing (BVP) is the gold standard for achieving CRT, but about 30%–40% of patients do not respond to BVP‐CRT. Recent studies showed that left bundle branch pacing (LBBP) provided remarkable results in CRT. Therefore, we conducted a meta‐analysis aiming to compare LBBP‐CRT versus BVP‐CRT in HF patients. Methods: We systematically searched the electronic databases for studies published from inception to December 29, 2022 and focusing on LBBP‐CRT versus BVP‐CRT in HF patients. The primary endpoint was HF hospitalization. The effect size was estimated using a random‐effect model as Risk Ratio (RR) and mean difference (MD). Results: Ten studies enrolling 1063 patients met the inclusion criteria. Compared to BVP‐CRT, LBBP‐CRT led to significant reduction in HF hospitalization [7.9% vs.14.5%; RR: 0.60 (95%CI: 0.39–0.93); p =.02], QRSd [MD: 30.26 ms (95%CI: 26.68–33.84); p <.00001] and pacing threshold [MD: −0.60 (95%CI: −0.71 to −0.48); p <.00001] at follow up. Furthermore, LBBP‐CRT improved LVEF [MD: 5.78% (95%CI: 4.78–6.77); p <.00001], the rate of responder [88.5% vs.72.5%; RR: 1.19 (95%CI: 1.07–1.32); p =.002] and super‐responder [60.8% vs. 36.5%; RR: 1.56 (95%CI: 1.27–1.91); p <.0001] patients and the NYHA class [MD: −0.42 (95%CI: −0.71 to −0.14); p <.00001] compared to BVP‐CRT. Conclusion: In HF patients, LBBP‐CRT was superior to BVP‐CRT in reducing HF hospitalization. Further significant benefits occurred within the LBBP‐CRT group in terms of QRSd, LVEF, pacing thresholds, NYHA class and the rate of responder and super‐responder patients. [ABSTRACT FROM AUTHOR]

Background: The increase of the incidence of human papillomavirus dependent oropharyngeal squamous cell carcinoma is alarming, although we have greatly progressed in the classification and staging of this disease. We now know that human papillomavirus related oropharyngeal squamous cell carcinoma is a sub‐type of head and neck squamous cell carcinoma with favourable prognosis and good response to therapy that needs a proper system of classification and staging. Thus, in routine practice it is essential to test patients for the presence of human papillomavirus. The most popular technique to assess human papillomavirus status is immunohistochemistry on biopsy samples with p16, which is an excellent surrogate for high‐risk human papillomavirus infection. Another highly sensitive and specific tissue‐based technique for the detection of human papillomavirus is RNAscope In situ hybridization that has a prohibitive cost, limiting its use in routine practice. Radiomics is an artificial intelligence based non‐invasive method of computational analysis of computed tomography, magnetic resonance imaging, positron emission tomography, and ultrasound images. Methods: In this review, we summarise the last findings of radiomics applied to human papillomavirus associated oropharyngeal squamous cell carcinoma. Results: A growing body of evidence suggest that radiomics is able to characterise and detect early relapse after treatment, and enable development of tailored therapy of human papillomavirus positive oropharyngeal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing allogeneic stem‐cell transplantation (allo‐SCT) have reduced responses to vaccines due to immunosuppressive status linked to GvHD prophylaxis and treatment. In our study, we compared humoral responses to anti‐SARS‐CoV‐2 mRNA vaccine, and infection onset, according to patients and transplant features; we also evaluated cellular response in patients without seroconversion. Methods: We tested antibodies titer after second and third vaccine doses. Antibodies were detected through an immune‐enzymatic assay. In a patients' subgroup without seroconversion, we tested cell‐mediated responses evaluating interferon‐gamma release by T‐lymphocytes exposed to virus spike protein. Results: Seroconversion rate increased from 66% at 30 days to 81% at 90 days after the second dose; it was 97% at 150 days after the third dose. We found a significant association between seroconversion after the second dose and two variables: shorter interval between allo‐SCT and vaccination; ongoing immunosuppression. Twelve of 19 patients (63%) without antibodies after the second dose did not show cellular responses. Nineteen percent of patients developed SARS‐CoV‐2 infection after the third dose, with favorable outcome in all cases. Patients within 12 months after allo‐SCT showed a significantly higher infection risk. Conclusions: Our study suggests that an interval shorter than 12 months between allo‐SCT and first vaccine dose and/or ongoing immunosuppression were associated with humoral and cellular response deficiency after two doses. Third dose induced an increased and sustained humoral response in the majority of patients. However, patients within 1 year after allo‐SCT remained at higher infection risk and may be candidate for prophylaxis with anti‐SARS‐CoV‐2 monoclonal antibodies. [ABSTRACT FROM AUTHOR]

Biliary anatomic variations are usually asymptomatic, but they may cause problems in diagnostic investigations and interventional and surgical procedures, increasing both their technical difficulty and their postoperative complication rates. The aim of the present study was to evaluate the prevalence of anatomic variations in the intrahepatic biliary ducts (IHBD) in relation to demographical and clinical characteristics in a large study population requiring magnetic resonance cholangiopancreatography (MRCP) for various clinical conditions. The possible association between IHBD and extrahepatic biliary ducts (EHBD) variants was then explored. From January 2017 to May 2019, 1004 patients underwent MRCP. Demographical and clinical data were collected. IHBD and EHBD anatomy were recorded and the EHBD anatomy was classified using both qualitative and quantitative classifications. The presence of a type 3 EHBD variant (an abnormal proximal cystic duct [CD] insertion) in both qualitative and quantitative classifications and an intrapancreatic CD were associated with the presence of IHBD variants at univariate analysis (p = 0.008, p = 0.019, and p = 0.001, respectively). The presence of a posterior or medial insertion of the CD into the EHBD was a strong predictive factor of the presence of IHBD variants both at uni‐ and multivariate analysis (p = 0.002 and p = 0.003 for posterior insertion and p = 0.002 and p = 0.002 for medial insertion, respectively). The presence of gallstones on MRCP resulted in a strong predictor of the presence of an anatomical variant of the IHBD both at uni‐ and multivariate analysis (p = 0.027 and p = 0.046, respectively). In conclusion, the presence of a type 3 variant of the EHBD, an intrapancreatic CD and, especially, a posterior/medial CD insertion into the EHBD represent predictive factors of the concomitant presence of IHBD variants, thus radiologists must be vigilant when encountering these EHBD configurations and always remember to "look up" at the IHBD. Finally, the presence of an IHBD variant is a strong predictive factor of gallstones. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of Coronary Artery Disease (CAD) plays a key role to prevent adverse cardiac events such as myocardial infarction and Left Ventricular (LV) dysfunction. Myocardial Work (MW) indices derived from echocardiographic speckle tracking data in combination with non‐invasive blood pressure recordings seems promising to predict CAD even in the absence of impairments of standard echocardiographic parameters. Our aim was to compare the diagnostic accuracy of MW indices to predict CAD and to assess intra‐ and inter‐observer variability of MW through a meta‐analysis. Methods: Electronic databases were searched for observational studies evaluating the MW indices diagnostic accuracy for predicting CAD and intra‐ and inter‐observer variability of MW indices. Pooled sensitivity, specificity, and Summary Receiver Operating Characteristic (SROC) curves were assessed. Results: Five studies enrolling 501 patients met inclusion criteria. Global Constructive Work (GCW) had the best pooled sensitivity (89%) followed by GLS (84%), Global Work Index (GWI) (82%), Global Work Efficiency (GWE) (80%), and Global Wasted Work (GWW) (75%). GWE had the best pooled specificity (78%) followed by GWI (75%), GCW (70%), GLS (68%), and GWW (61%). GCW had the best accuracy according to SROC curves, with an area under the curve of 0.86 compared to 0.84 for GWI, 0.83 for GWE, 0.79 for GLS, and 0.74 for GWW. All MW indices had an excellent intra‐ and inter‐observer variability. Conclusions: GCW is the best MW index proving best diagnostic accuracy in the prediction of CAD with an excellent reproducibility. [ABSTRACT FROM AUTHOR]

Aim: Melatonin seems to have a positive impact on the brain–gut axis and many direct and indirect effects on the gastrointestinal tract. This trial aimed at assessing the efficacy of melatonin combined with Lactobacillus Rhamnosus GG given in the treatment of paediatric patients with functional abdominal pain disorders. Methods: Forty‐two patients aged 4–18 years old who fulfilled the Rome IV Diagnostic Criteria for functional abdominal pain disorders were enrolled. Melatonin 3 or 5 mg in combination with Lactobacillus Rhamnosus GG (group 1, n = 22) or a placebo in combination with Lactobacillus Rhamnosus GG (control group, n = 20) were taken in the evening for a period of 4 weeks. The study duration was 12 weeks. The primary study endpoint was represented by clinical improvement at week 12 – defined as at least a 50% reduction in mean abdominal pain index (API) from baseline to week 12. Results: The mean API was reduced by more than 50% between T0 and T2 in the group of children treated with melatonin. However, the difference in the distributions of the variations of the scores between the two groups was not significant between T0 and T2 (P = 0.082), while it was significant between T0 and T1 (P = 0.001). Similar results were obtained by analysing the API variables 'weekly frequency of pain' (item 1) and 'perceived intensity of pain' (item 4) individually. Conclusions: This is the first study to investigate the role of the combination of melatonin and Lactobacillus Rhamnosus GG in the treatment of children with functional abdominal pain disorders. Melatonin combined with Lactobacillus Rhamnosus GG can be considered a therapeutic option for these conditions in children. [ABSTRACT FROM AUTHOR]

Biopolymers emerged in recent years as a promising alternative for a more sustainable manufacturing of electrochemical energy storage systems. In fact, for environmentally friendly aqueous systems, fluorinated polymers are usually adopted. For this reason, substituting these polymers with water processable binders could improve the overall environmental impact of the device. In this study, a low – cost and environmentally friendly modification of chitosan binder for self‐standing activated carbon electrodes operating in Na ion, aqueous electrochemical double layer capacitors is reported and discussed. [ABSTRACT FROM AUTHOR]

Background and purpose: Upper limb (UL) function is often affected in people with multiple sclerosis (PwMS) and is typically assessed through objective measures, including the Nine Hole Peg Test (9‐HPT), Box and Block Test (BBT), and Hand Grip Strength (HGS). It is important to include the subjective perspective of PwMS in the assessment. This study aims to evaluate associations between Manual Ability Measure‐36 (MAM‐36) and 9‐HPT, BBT, and HGS in MS. Methods: The cross‐sectional study included five Italian centers. Inclusion criteria were age ≥ 18 years, MS diagnosis, and stable disease course. Exclusion criteria were bilateral UL paralysis, and concomitant orthopedic or neurological diseases. Results: A total of 199 PwMS were included: 128 female, mean age = 50.7 ± 13.0 years, 119 relapsing–remitting MS (RRMS), 31 primary and 49 secondary progressive MS, mean disease duration = 14.0 ± 10.4, years, mean Expanded Disability Status Scale (EDSS) = 4.6 ± 2.0. The MAM‐36 showed small correlations with 9‐HPT, BBT, and HGS. Correlations between MAM‐36 and 9‐HPT and BBT were highest among subjects with EDSS ≥ 6 and progressive MS. MAM‐36 and HGS showed the highest correlations in subjects with EDSS ≤ 5 and RRMS. Combining 9‐HPT and HGS provided the strongest predictive power over the MAM‐36. Conclusions: Correlations between objective measures and MAM‐36 were small to moderate, meaning that objective measures do not match subjects' perception of UL function. The combination of 9‐HPT and HGS measures can help improve the assessment of UL function in activities of daily living. [ABSTRACT FROM AUTHOR]

Aims: The efficacy of the transurethral convective interstitial radiofrequency water vapor thermal ablation of the prostate with the Rezūm system for the treatment of male lower urinary tract symptom due to benign prostatic hyperplasia is well proven. The improvement of urodynamic parameters obtained from a simple uroflowmetry cannot measure the effect of water vapor injection on the bladder outlet obstruction. Methods: This monocentric retrospective pilot study analyzes the data of pressure‐flow studies performed before and after 17 Rezūm procedures to answer the question whether thus obtained ablation of prostate tissue has a disobstructive effect on the bladder outlet. Results: All the functional outcomes were consistently improved after the procedure, with a median flowrate increase of 5.1 ml/s (p = 0.0022) and a median postvoid residual urine (PVR) reduction of 100 ml (p = 0.0042). The prostate volume was reduced by 40% (p < 0.0001) and the median Bladder Outlet Obstruction Index (BOOI) reduction was 53.8 (p < 0.0001). Conclusions: These data show that the possibility to significantly reduce the obstruction grade with even a single Rezūm procedure is concrete and seems to be independent from the degree of the obstruction grade. [ABSTRACT FROM AUTHOR]

Introduction: The implantable cardioverter defibrillator (ICD) has been demonstrated to successfully prevent sudden cardiac death (SCD) in children and young adults. A wide range of device‐related complications/malfunctions have been described, which depend on the intrinsic design of the defibrillation system (transvenous‐implantable cardioverter defibrillator [TV‐ICD] vs. subcutaneous‐implantable cardioverter defibrillator [S‐ICD]). Objective: To compare the device‐related complications and inappropriate shocks with TV‐ICD versus S‐ICD. Methods and Results: Electronic databases were queried for studies focusing on the prevention of SCD in children and young adults with TV‐ICD or S‐ICD. The effect size was estimated using a random‐effect model as odds ratio (OR) and relative 95% confidence interval (CI). The primary endpoint was a composite of any device‐related complications and inappropriate shocks. We identified a total of five studies including 236 patients (Group S‐ICD: 76 patients; Group TV‐ICD: 160 patients) with a mean follow‐up time of 54.2 ± 24.9 months. S‐ICD implantation contributed to a significant reduction in the risk of the primary endpoint of any device‐related complications and inappropriate shocks (OR: 0.18; 95% CI: 0.05–0.73; p =.02). S‐ICD was also associated with a significantly lower incidence of inappropriate shocks (OR: 0.28; 95% CI: 0.11–0.74; p =.01) and lead‐related complications (OR: 0.18; 95% CI: 0.05–0.66; p =.01). A trend toward a higher risk of pocket complications (OR: 5.91; 95% CI: 0.98–35.63; p =.05) was recorded in patients with S‐ICD. Conclusion: Children and young adults undergoing S‐ICD implantation may have a lower risk of a composite of device‐related complications and inappropriate shocks, compared to TV‐ICD patients. [ABSTRACT FROM AUTHOR]

As a power electronic converter with bidirectional energy transmission, the Dual Active Bridge (DAB) has a broad application prospect in the electrical power distribution system of hybrid‐electric flight. For the DAB application in the electrical power distribution system, high efficiency and high reliability are envisaged due to the mission‐critical nature of the application. A new pulse width modulation optimization control strategy is proposed, which is based on the feedback temperature fluctuations of the GaN (Gallium Nitride) power transistors, to improve the lifetime of the whole circuit. The complete topology and simulations of the DAB converter are carried out in PLECS. Detailed simulation results manifest the precise lifetime of the GaN power transistors and verify the accuracy of the new optimization control strategy. Meanwhile, Insulated Gate Bipolar Translator is set as a control group to compare the lifetime of conventional silicon‐based power devices with the GaN power transistor. Hardware In Loop platform test is built to further validate the proposed method. [ABSTRACT FROM AUTHOR]

Background and purpose: Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID‐19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID‐19 in MS patients and identify all factors associated with their manifestation. Method: Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number. Results: From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID‐19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p = 0.005) and more in smoker patients (OR 1.39; p = 0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p = 0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p = 0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p = 0.008). Some disease‐modifying therapies were associated with greater frequencies of certain COVID‐19 symptoms (association between anti‐CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p = 0.05). Differences in frequencies between the three waves were found for flu‐like symptoms (G1, p = 0.024), joint or muscle pain (G2, p = 0.013) and ageusia and anosmia (G5, p < 0.001). All cases should be referred to variants up to Delta. Conclusion: Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID‐19 symptoms. [ABSTRACT FROM AUTHOR]

We investigated the mechanisms leading to the specific recognition of Guanine Guadruplex (G4) by DARPins peptides, which can lead to the design of G4 s specific sensors. To this end we carried out all‐atom molecular dynamic simulations to unravel the interactions between specific nucleic acids, including human‐telomeric (h‐telo), Bcl‐2, and c‐Myc, with different peptides, forming a DARPin/G4 complex. By comparing the sequences of DARPin with that of a peptide known for its high affinity for c‐Myc, we show that the recognition cannot be ascribed to sequence similarity but, instead, depends on the complementarity between the three‐dimensional arrangement of the molecular fragments involved: the α‐helix/loops domain of DARPin and the G4 backbone. Our results reveal that DARPins tertiary structure presents a charged hollow region in which G4 can be hosted, thus the more complementary the structural shapes, the more stable the interaction. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate how the COVID-19 pandemic influenced ERAS program application in colorectal surgery across hospitals in the Lazio region (central district in Italy) participating in the "Lazio Network" project. Methods: A multi-institutional database was constructed. All patients included in this study underwent elective colorectal surgery for both malignant and benign disease between January 2019 and December 2020. Emergency procedures were excluded. The population was divided into 2 groups: a pre-COVID-19 group (PG) of patients operated on between February and December 2019 and a COVID-19 group (CG) of patients operated on between February and December 2020, during the first 2 waves of the pandemic in Italy. Results: The groups included 622 patients in the PG and 615 in the CG treated in 8 hospitals of the network. The mean number of items applied was higher in the PG (65.6% vs. 56.6%, p < 0.001) in terms of preoperative items (64.2% vs. 50.7%, p < 0.001), intraoperative items (65.0% vs. 53.3%, p < 0.001), and postoperative items (68.8% vs. 63.2%, p < 0.001). Postoperative recovery was faster in the PG, with a shorter time to first flatus, first stool, autonomous mobilization and discharge (6.82 days vs. 7.43 days, p = 0.021). Postoperative complications, mortality and reoperations were similar among the groups. Conclusions: The COVID-19 pandemic had a negative impact on the application of ERAS in the centers of the "Lazio Network" study group, with a reduction in adherence to the ERAS protocol in terms of preoperative, intraoperative and postoperative items. In addition, in the CG, the patients had worse postoperative outcomes with respect to recovery and discharge. [ABSTRACT FROM AUTHOR]

Background and Aims: In oncology, there is increasing talk of personalized treatment and shared decision‐making (SDM), especially when multiple treatment options are available with different outcomes depending on patient preference. The present study aimed to define the set of main dimensions and relative tools to assess the Value brought to patients from a Breast Cancer's Clinical pathway structured according to a dynamic SDM framework. Methods: Starting from our previous systematic review of the literature, a deep search of the main evidence‐based and already validated questionnaires was carried out. In the second phase, to corroborate this grid, a Delphi survey was conducted to assess each questionnaire identified for each dimension, against the following seven value‐based criteria: Clinical Benefit, Safety, Care Team Well Being, Patient Reported Outcomes Measures, Green Oncology, Impact on Health Budget, and Genomic Profile. Results: The resulting 7‐dimension questionnaire is composed of 72 questions. Of these, some quantitatively and objectively assess the evolution of the patient's disease state, whereas others aim to ask patients about their active involvement in decisions affecting them and to investigate whether they were free to explore their preferences. Furthermore, to frame the analyzed phenomenon at the right time, for each questionnaire section, the specific, evidence‐based timing of administration is indicated. Conclusion: The resulting questionnaire is validated in its entirety and it is composed of a set of questions and relative time point for data collections to assess the Value brought to patients undertaking a Breast Cancer's Clinical pathway, structured according to a dynamic SDM framework. It constitutes a quantitative instrument to integrate patient centeredness with a personalized perspective in the care management of women with breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate a variety of techniques, and their anatomical and functional results, for the treatment of optic disc pit maculopathy (ODP‐M). A secondary aim was to report on results of secondary procedures in cases of initial failure or recurrence. Methods: Multicentre retrospective study of 95 eyes with ODP‐M, treated by 25 surgeons from 12 countries. Primary outcomes were anatomical resolution of subretinal fluid (SRF), intraretinal fluid (IRF) and visual acuity (VA) at 12 months. Results: Higher rates of SRF and IRF resorption were achieved in eyes treated with pars plana vitrectomy (PPV) compared to external laser with or without tamponade: 64/72 (88.9%) versus 8/14 (57.1%) for SRF (p = 0.003), and 50/59 (84.7%) versus 3/10 (30%) for IRF (p = 0.002). The addition of juxtapapillary laser or internal limiting membrane (ILM) peel during PPV did not improve SRF or IRF resolution. Pars plana vitrectomy (PPV) with tamponade and PPV with tamponade plus endolaser were associated with significant visual gain. In the former group, VA improved from a mean of logMAR 0.91 (20/162), to a mean of logMAR 0.52 (20/66) at 12 months; in the latter group, VA improved from a mean of logMAR 0.82 (20/132) to a mean of logMAR 0.47 (20/59) at 12 months. Retreatments were performed in 14 eyes (15.7%), only enhancing anatomical outcomes. Conclusion: Vitrectomy with tamponade had better final outcomes than external laser treatment with or without gas tamponade. Laser endophotocoagulation and ILM peel provided no additional benefit. A secondary treatment resulted in anatomical but not functional improvement. [ABSTRACT FROM AUTHOR]