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Background and aims: Candidate selection for lung transplantation (LuTx) is pivotal to ensure individual patient benefit as well as optimal donor organ allocation. The impact of coronary artery disease (CAD) on post-transplant outcomes remains controversial. We provide comprehensive data on the relevance of CAD for short- and long-term outcomes following LuTx and identify risk factors for mortality. Methods: We retrospectively analyzed all adult patients (≥ 18 years) undergoing primary and isolated LuTx between January 2000 and August 2021 at the LMU University Hospital transplant center. Using 1:1 propensity score matching, 98 corresponding pairs of LuTx patients with and without relevant CAD were identified. Results: Among 1,003 patients having undergone LuTx, 104 (10.4%) had relevant CAD at baseline. There were no significant differences in in-hospital mortality (8.2% vs. 8.2%, p > 0.999) as well as overall survival (HR 0.90, 95%CI [0.61, 1.32], p = 0.800) between matched CAD and non-CAD patients. Similarly, cardiovascular events such as myocardial infarction (7.1% CAD vs. 2.0% non-CAD, p = 0.170), revascularization by percutaneous coronary intervention (5.1% vs. 1.0%, p = 0.212), and stroke (2.0% vs. 6.1%, p = 0.279), did not differ statistically between both matched groups. 7.1% in the CAD group and 2.0% in the non-CAD group (p = 0.078) died from cardiovascular causes. Cox regression analysis identified age at transplantation (HR 1.02, 95%CI [1.01, 1.04], p < 0.001), elevated bilirubin (HR 1.33, 95%CI [1.15, 1.54], p < 0.001), obstructive lung disease (HR 1.43, 95%CI [1.01, 2.02], p = 0.041), decreased forced vital capacity (HR 0.99, 95%CI [0.99, 1.00], p = 0.042), necessity of reoperation (HR 3.51, 95%CI [2.97, 4.14], p < 0.001) and early transplantation time (HR 0.97, 95%CI [0.95, 0.99], p = 0.001) as risk factors for all-cause mortality, but not relevant CAD (HR 0.96, 95%CI [0.71, 1.29], p = 0.788). Double lung transplant was associated with lower all-cause mortality (HR 0.65, 95%CI [0.52, 0.80], p < 0.001), but higher in-hospital mortality (OR 2.04, 95%CI [1.04, 4.01], p = 0.039). Conclusion: In this cohort, relevant CAD was not associated with worse outcomes and should therefore not be considered a contraindication for LuTx. Nonetheless, cardiovascular events in CAD patients highlight the necessity of control of cardiovascular risk factors and a structured cardiac follow-up. [ABSTRACT FROM AUTHOR]

Background: Studies have demonstrated patients hold different expectations for female physicians compared to male physicians, including higher expectations for patient-centered communication and addressing socioeconomic or emotional needs. Recent evidence indicates this gender disparity extends to the electronic health record (EHR). Similar studies have not been conducted with resident physicians. Objective: This study seeks to characterize differences in EHR workload for female resident physicians compared to male resident physicians. Design: This study evaluated 12 months of 156 Mayo Clinic internal medicine residents' inbasket data from July 2020 to June 2021 using Epic's Signal and Physician Efficiency Profile (PEP) data. Excel, BlueSky Statistics, and SAS analytical software were used for analysis. Paired t-tests and analysis of variance were used to compare PEP data by gender and postgraduate year (PGY). "Male" and "female" were used in substitute for "gender" as is precedent in the literature. Subjects: Mayo Clinic internal medicine residents. Main Measures: Total time spent in EHR per day; time in inbasket and notes per day; time in notes per appointment; number of patient advice requests made through the portal; message turnaround time. Key Results: Female residents received more patient advice requests per year (p = 0.004) with an average of 86.7 compared to 68, resulting in 34% more patient advice requests per day worked (p < 0.001). Female residents spent more time in inbasket per day (p = 0.002), in notes per day (p < 0.001), and in notes per appointment (p = 0.001). Resident panel comparisons revealed equivocal sizes with significantly more female patients on female (n = 55) vs male (n = 34) resident panels (p < 0.001). There was no difference in message turnaround time, total messages, or number of results received. Conclusions: Female resident physicians experience significantly more patient-initiated messages and EHR workload despite equivalent number of results and panel size. Gender differences in inbasket burden may disproportionally impact the resident educational experience. [ABSTRACT FROM AUTHOR]

The historical restriction of magnetic resonance imaging (MRI) for patients with cardiac implantable electronic devices (CIEDs) has been lifted by certified MRI-conditional systems in recent years. Mixed-brand CIED systems consisting of a generator from one manufacturer and at least one lead from another manufacturer are not certified for MRI. We evaluated the temporal trend in the prevalence of mixed-brand systems in the era of MRI-conditional systems. Data were analyzed on 5853 CIEDs implanted de novo between 2012 and 2022 in 81 Italian centers linked to the nationwide Home Monitoring Expert Alliance network. The percentage of mixed-brand implants was calculated by device type (pacemaker, implantable cardioverter-defibrillator [ICD], cardiac resynchronization therapy [CRT] device) and over time. A mixed-brand system was implanted in 4.1% (95% CI, 3.6-4.6%) of analyzed patients or, by device type, in 4.5% (3.5-5.7%) of pacemaker patients, 1.1% (0.7-1.7%) of ICD patients, and 6.8% (5.7-7.9%) of CRT pacemaker/defibrillator patients (p < 0.001). Prevalence of mixed-brand implants exhibited significant temporal fluctuations, first declining from 6.6% (2012–2014) to 1.3% (2019), and then increasing to 5.1% (2022). Temporal changes were statistically significant for pacemakers (p < 0.001) and CRT devices (p = 0.001), but not for ICDs (p = 0.438). In the decade between 2012 and 2022, mixed-brand CIED systems were more prevalent in patients treated with pacemakers and CRT devices than in ICD recipients. A decline in the prevalence of mixed-brand systems was observed after the introduction of MRI-conditional systems, reaching a minimum in 2019, followed by a progressive increase in the subsequent years. [ABSTRACT FROM AUTHOR]

Phenotypic plasticity allows a plant cell to alter its structure and function in response to external pressure. This adaptive phenomenon has also been important in the evolution of plants including the emergence of land plants from a streptophyte alga. Penium margaritaceum is a unicellular zygnematophyte (i.e., the group of streptophyte algae that is sister to land plants) that was employed in order to study phenotypic plasticity with a focus on the role of subcellular expansion centers and the cell wall in this process. Live cell fluorescence labeling, immunofluorescence labeling, transmission electron microscopy, and scanning electron microscopy showed significant subcellular changes and alterations to the cell wall. When treated with the actin-perturbing agent, cytochalasin E, cytokinesis is arrested and cells are transformed into pseudo-filaments made of up to eight or more cellular units. When treated with the cyclin-dependent kinase (CDK) inhibitor, roscovitine, cells converted to a unique phenotype with a narrow isthmus zone. [ABSTRACT FROM AUTHOR]

Introduction: The ratio between tricuspid annular plane systolic excursion (TAPSE) and estimated pulmonary artery systolic pressure (PASP) has been shown to be a reliable, non-invasive surrogate of the right ventricular-pulmonary artery (RV-PA) coupling. The present study analysed the association between TAPSE/PASP and response to cardiac resynchronization therapy (CRT) and the prognostic role of RV-PA in patients undergoing CRT implantation. The primary endpoints were: the association between baseline TAPSE/PASP and CRT response/cardiovascular and all-cause death. Methods and Results: All patients having undergone CRT implantation in our Center from 2016 to 2020 were included in our retrospective analysis. The RV-PA coupling was assessed by echocardiography at baseline and 1 year follow up in CRT recipients. The cut-off value of TAPSE/PASP resulted from ROC curve analysis (i.e.<0.33 mm/mmHg). A total of 229 patients (age 69.9 ± 10.1 years; 77.7% men) were included. During a mean follow-up of 44.2 ± 17.9 months, 40 (17.5%) patients died. The baseline value of TAPSE/PASP was not significantly associated with CRT response. Patients with a more impaired TAPSE/PASP ratio had significantly worse survival rates. On multivariate Cox regression, only TAPSE/PASP ratio and estimated glomerular filtration rate were independently associated with all-cause death. Finally, the TAPSE/PASP ratio significantly increased after CRT implantation in the group of "responders" whereas it did not change in 'non-responders'. Conclusions: The baseline value of TAPSE/PASP ratio was not associated with CRT response. However, the TAPSE/PASP ratio was a strong predictor of both all-cause and cardiovascular death in CRT recipients. [ABSTRACT FROM AUTHOR]

In the debate on international waste trade, the focus on resource efficiency and recycling has gradually begun to accompany the focus on negative environmental externalities. In this context, we examine the impact of extended producer responsibility (EPR) on the export of waste batteries (WB). EPR is considered as a key policy for the "marketization of waste". WB are a hazardous waste that also contain a high concentration of critical raw materials. As such, they are of strategic importance for the recovery of critical resources, while at the same time requiring proper environmental management. Therefore, it is crucial to understand where WB are treated and how this is affected by related policies. Our results, based on difference-in-difference models in a gravity framework, show a consistent increase in WB exports after EPR implementation compared to the trend for other wastes. This result is likely to be an indirect consequence of the ability of EPR to support growth in waste collection rates, more accurate tracking of transboundary waste flows, and specialization of national waste management systems. In particular, WB exports appear to be directed to countries with more advanced waste management systems, more stringent environmental regulations, and limited endowments of the mineral resources typically contained in batteries. [ABSTRACT FROM AUTHOR]

[11C]Carfentanil ([11C]CFN) is the only selective carbon-11 labeled radiotracer currently available for positron emission tomography (PET) imaging of mu opioid receptors (MORs). Though used extensively in clinical research, [11C]CFN has not been thoroughly characterized as a tool for preclinical PET imaging. As we were occasionally observing severe vital sign instability in rat [11C]CFN studies, we set out to investigate physiological effects of CFN mass and to explore its influence on MOR quantification. In anesthetized rats (n = 15), significant dose-dependent PCO2 increases and heart rate decreases were observed at a conventional tracer dose range (IV, > 100 ng/kg). Next, we conducted baseline and retest [11C]CFN PET scans over a wide range of molar activities. Baseline [11C]CFN PET studies (n = 27) found that nondisplaceable binding potential (BPND) in the thalamus was positively correlated to CFN injected mass, demonstrating increase of MOR availability at higher injected CFN mass. Consistently, when CFN injected mass was constrained < 40 ng/kg (~ 10% MOR occupancy in rats), baseline MOR availability was significantly decreased. For test–retest variability (TRTV), better reproducibility was achieved by controlling CFN injected mass to limit the difference between scans. Taken together, we report significant cardiorespiratory depression and a paradoxical influence on baseline MOR availability at conventional tracer doses in rats. Our findings might reflect changes in cerebral blood flow, changes in receptor affinity, or receptor internalization, and merits further mechanistic investigation. In conclusion, rat [11C]CFN PET requires stringent quality assurance of radiotracer synthesis and mass injected to avoid pharmacological effects and limit potential influences on MOR quantification and reproducibility. [ABSTRACT FROM AUTHOR]

We present an analysis of the recent near threshold BESIII data for the nucleon time-like effective form factors. The damped oscillation emerging from the subtraction of the dipole formula is treated in non-perturbative-QCD, making use of the light cone distribution amplitudes expansion. Non-perturbative effects are accounted for by considering Q 2 -dependent coefficients in such expansions, whose free parameters are determined by fitting to the proton and neutron data. Possible implications and future analysis have been discussed. [ABSTRACT FROM AUTHOR]

Background: Catheter ablation has become an established treatment option for premature ventricular complexes (PVCs). The use of fluoroscopy exposes patients and medical staff to potentially harmful stochastic and deterministic effects of ionizing radiations. We sought to analyze procedural outcomes in terms of safety and efficacy using a "zero fluoroscopy" approach for catheter ablation of PVCs. Methods: The present retrospective, multicenter, observational study included 131 patients having undergone catheter ablation of PVCs using "zero fluoroscopy" between 2019 and 2020 in four centers compared with another group who underwent the procedure with fluoroscopy. Results: Median age was 51.0 ± 15.9 years old; males were 77 (58.8%). Among the study population, 26 (19.8%) had a cardiomyopathy. The most frequent PVC origin was right ventricular outflow tract (55%) followed by the left ventricle (16%), LVOT and cusps (13.7%), and aortomitral continuity (5.3%). Acute suppression of PVC was achieved in 127 patients (96.9%). At 12 months, a complete success was documented in 109 patients (83.2%), a reduction in PVC burden in 18 patients (13.7%), and a failure was recorded in four patients (3.1%). Only two minor complications occurred (femoral hematoma and arteriovenous fistula conservatively treated). Conclusions: The PVC ablation with a "zero" fluoroscopy approach appears to be a safe procedure with no major complications and good rates of success and recurrence in our multicenter experience. [ABSTRACT FROM AUTHOR]

The Irrational Food Beliefs Scale (IFBS) is a self-report questionnaire comprising 57 items, 41 of which in the irrational food beliefs subscale, assessing cognitive distortions and inappropriate attitudes and beliefs about food. This study aimed to propose the Italian version of the IFBS and examine its psychometric properties. The tool was translated into Italian and administered to 503 Italian-speaking patients with obesity and 45 healthy controls. The clinical group also completed the Eating Disorder Examination (EDE) interview, and the Symptom Checklist-90 (SCL-90). Principal factor analysis identified that 51.6% of the variance was accounted for by six factors, which we termed 'self-deception on eating and weight control', 'beliefs about eating and emotion regulation', 'low tolerance for eating control', 'beliefs about eating and hedonic pleasure', 'beliefs about dieting', and 'all-or-nothing thinking about eating.' The IFBS global and subscale scores were partially correlated with eating-disorder and general psychopathology. Significantly higher scores were found in patients with obesity and binge-eating disorder than in those with obesity without binge-eating disorder. Overall, the study demonstrated the good psychometric properties of the Italian version of the IFBS and validated its use in Italian-speaking patients with obesity. [ABSTRACT FROM AUTHOR]

Glioblastoma (GB) is the most common primary brain tumor in adults and carries a dismal prognosis, despite the best available treatment. The 2021 WHO Classification of CNS tumors incorporated molecular profiling to better define the characteristics and prognosis of tumor types and subtypes. These recent advances in diagnosis have not yet resulted in breakthrough therapies capable of shifting the treatment paradigm. NT5E/CD73 is a cell surface enzyme that participates in a complex purinergic pathway in synergy with ENTPD1/CD39 producing extracellular adenosine (ADO) from ATP. ADO promotes tumor progression by inducing immunosuppression, stimulating adhesion, invasion, and angiogenesis. In this study, we performed an in silico analysis of 156 human glioblastoma samples in an unexplored public database to investigate the transcriptional levels of NT5E and ENTPD1. The analysis revealed a significant increase in transcription levels of the genes under study in GB samples versus non-tumor brain tissue samples, in concordance with previous studies. High transcriptional levels of NT5E or ENTPD1 were independently related to a decrease in overall survival (p = 5.4e-04; 1.1e-05), irrespective of the IDH mutation status. NT5E transcriptional levels were significantly higher in GB IDH wild-type patients compared to GB IDH-mutant; however, ENTPD1 levels showed no significant difference, p ≤ 0.001. This in silico study indicates the need for a deeper understanding of the purinergic pathway relation to GB development, also inspiring future population studies that could explore ENTPD1 and NT5E not only as prognostic markers but also as potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Neonatologist Performed Echocardiography (NPE) is one of the emerging technologies used to evaluate Systemic Blood Flow (SBF) in term and preterm infants. Right Ventricular Output (RVO) can assess SBF correctly in the absence of significant interatrial or interventricular shunts, even in the presence of a large patent ductus arteriosus (PDA), but only few studies evaluated inter-observer variability in neonates. Furthermore, measuring pulmonary peak flow (PF) provides a simple screening tool for low SBF state, easier and faster to perform than RVO; no previous studies evaluated PF inter-observer variability. To describe inter-observer variability of RVO and PF measurement in neonates. We conducted a prospective observational study in term and preterm infants admitted to the Neonatal Intensive Care Unit (NICU). Echocardiographic examinations were performed by two expert neonatologists, blinded to each other. Recordings were analyzed off-line to assess RVO and PF variability between observers. We analyzed a cohort of 33 neonates, 17 of them born prematurely. Inter-observer mean difference for RVO was 22,1 mL/kg/min (p = 0.005); the biggest discrepancy was due to pulmonary valve diameter measurement (p = 0.0001). Inter-observer mean difference for PF measurement was not statistically significant. We found a statistically significant inter-observer variability for RVO measurement, consistent with previous reports; PF instead showed low inter-observer variability. For this reason, PF could be evaluated in future studies as a surrogate for RVO in both term and preterm infants, especially in emergency conditions or in presence of a poor echocardiographic window. [ABSTRACT FROM AUTHOR]

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Radiative corrections are crucial for modern high-precision physics experiments, and are an area of active research in the experimental and theoretical community. Here we provide an overview of the state of the field of radiative corrections with a focus on several topics: lepton–proton scattering, QED corrections in deep-inelastic scattering, and in radiative light-hadron decays. Particular emphasis is placed on the two-photon exchange, believed to be responsible for the proton form-factor discrepancy, and associated Monte-Carlo codes. We encourage the community to continue developing theoretical techniques to treat radiative corrections, and perform experimental tests of these corrections. [ABSTRACT FROM AUTHOR]

Introduction: The signal transducer and activator of transcription (STAT1) gain-of-function (GOF) syndrome accounts for most cases of chronic mucocutaneous candidiasis but is characterized by a broader clinical phenotype that may include bacterial, viral, or invasive fungal infections, autoimmunity, autoinflammatory manifestations, vascular complications, or malignancies. The severity of lymphopenia may vary and influence the infectious morbidity. Methods: In our cohort of seven STAT1-GOF patients, we investigated the mechanisms that may determine T lymphopenia, we characterized the interferon gene signature (IGS) and analyzed the effect of ruxolitinib in reverting the immune dysregulation. Results: STAT1-GOF patients exhibited increased T lymphocyte apoptosis that was significantly augmented in both resting conditions and following stimulation with mitogens and IFNα, as evaluated by flow cytometry by Annexin V/ Propidium iodide assay. The JAK inhibitor ruxolitinib significantly reduced the IFNα-induced hyperphosphorylation of STAT1 and reverted the stimulation-induced T-cell apoptosis, in vitro. In two adult STAT1-GOF patients, the JAKinib treatment ameliorated chronic mucocutaneous candidiasis and lymphopenia. Most STAT1-GOF patients, particularly those who had autoimmunity, presented increased IGS that significantly decreased in the two patients during ruxolitinib treatment. Conclusion: In STAT1-GOF patients, T lymphocyte apoptosis is increased, and T lymphopenia may determine higher risk of severe infections. The JAKinib target therapy should be evaluated to treat severe chronic candidiasis and lymphopenia, and to downregulate the IFNs in patients with autoinflammatory or autoimmune manifestations. [ABSTRACT FROM AUTHOR]

This article discusses the challenges of performing catheter ablation for certain types of tachycardia in patients with a persistent left superior vena cava (PLSVC), a common venous anomaly. The presence of PLSVC can lead to the enlargement of the coronary sinus and the dislocation of common target sites for ablation. The article presents two case studies illustrating the difficulties encountered during ablation procedures in patients with PLSVC. The authors emphasize the importance of careful mapping and targeting of alternative sites for effective ablation. [Extracted from the article]

Handedness develops early in life, but the structural and functional brain connectivity patterns associated with it remains unknown. Here we investigate associations between handedness and the asymmetry of brain connectivity in 9- to 10-years old children from the Adolescent Brain Cognitive Development (ABCD) study. Compared to right-handers, left-handers had increased global functional connectivity density in the left-hand motor area and decreased it in the right-hand motor area. A connectivity-based index of handedness provided a sharper differentiation between right- and left-handers. The laterality of hand-motor connectivity varied as a function of handedness in unimodal sensorimotor cortices, heteromodal areas, and cerebellum (P < 0.001) and reproduced across all regions of interest in Discovery and Replication subsamples. Here we show a strong association between handedness and the laterality of the functional connectivity patterns in the absence of differences in structural connectivity, brain morphometrics, and cortical myelin between left, right, and mixed handed children.Handedness is thought to be associated with brain asymmetry. Here, the authors show distinct brain functional connectivity associated with left- vs. right-handed children, shedding light on early neural organization and its relationship with handedness. [ABSTRACT FROM AUTHOR]

Cancer is one of the major causes of death worldwide and the development of multidrug resistance (MDR) in cancer cells is the principal cause of chemotherapy failure. To gain insights into the specific mechanisms of MDR in cancer cell lines, we developed a novel method for the combined analysis of recently published datasets on drug sensitivity and CRISPR loss-of-function screens for the same set of cancer cell lines. For our analysis, we first selected cell lines that consistently exhibit drug resistance across several classes of compounds. We then identified putative resistance genes for each class of compound and used inferred gene regulatory networks (GRNs) to study possible mechanisms underlying the development of MDR in the identified cancer cell lines. We show that the same method of analysis can also be used to identify cell lines that consistently exhibit resistance to the gene knockout effect of the CRISPR-Cas9 technique and to study the possible underlying mechanisms. In the GRN associated to the drug resistant cell lines, we identify genes previously associated with resistance (UHMK1, RALYL, MGST3, USP9X, and ESRG), genes for which an indirect association can be identified (SPINK13, LINC00664, MRPL38, and EMILIN3), and genes that are found to be overexpressed in non-resistant cancer cell lines (MRPL38, EMILIN3 and RALYL). In the GRNs associated to the CRISPR-Cas9 resistance mechanism, none of the identified genes has been previously reported in the admittedly sparse literature on the subject. However, some of these genes have a common role: APBB2, RUNX1T1, ZBTB7C, and ISX regulate transcription, while APBB2, BTG3, ZBTB7C, SZRD1 and LEF1 have a function in regulating proliferation, suggesting a role for these two pathways. While our results are specific for the lung cancer cell lines we selected for this work, our method of analysis can be applied to cell lines from other tissues and for which the required data is available. [ABSTRACT FROM AUTHOR]

Mild traumatic brain injury (mTBI) is a common cause of admission to the Emergency Department (ED). Many patients are elderly on oral anticoagulant therapy (OAT) at increased risk of immediate and delayed intracranial hemorrhage (ICH). To investigate the frequency of delayed ICH (DICH) in old patients with mTBI in OAT and the occurrence of complications related to the ED stay. In this single-center retrospective study, we recruited all patients in OAT aged 65 and over, admitted for mTBI to the ED of our Hospital in Florence from March 2019 to February 2021. Clinical variables were collected and cranial computed tomography (CT) scans reviewed. The primary outcome was the frequency of DICH occurring within 30 days since the trauma after a first negative CT. Secondary outcomes included need of neurosurgical intervention and death for DICH, and hospital-related complications. Statistical analyses were conducted using IBM SPSS Statistics (version 22). Among 363 enrolled patients, there were 31 acute ICH (8.5%) at the first CT scan, while in the 316 negative included patients, 10 DICH (3.2%) were identified. Among the latter, no neurosurgical treatment, or death due to ICH occurred. Overall, 25 cases (6.9%) had iatrogenic complications during the 24-h observation period, often serious, such as respiratory failure after sedation due to restlessness, or COVID-19 infection. The low frequency of DICH and the occurrence of several iatrogenic complications suggest that the risk–benefit ratio of a 24-h ED observation is not advantageous in elderly with mTBI. [ABSTRACT FROM AUTHOR]

Since pedestrians are impacted by solar radiation differently, urban designers must evaluate solar radiation exposure of pedestrian paths adopting an inclusive approach. This paper proposes a maximum threshold of direct solar radiation exposure for pedestrians based on activity, user profile and environmental conditions, defined as the difference between the energy consumption before feeling exhausted and the energy cost of walking. Two users of diverse walking abilities, a young adult and an elderly person with mobility impairment, were characterised by metabolic activity, walking speed and maximum energy capacity. Based on the theoretical framework, the energy budget of young adults to cope with thermal stress was set as three times higher than for the elderly. This framework was used to quantify the contribution of direct solar radiation to energy balance and then classify walkability during clear-sky summer hours; the term 'walkable' referred to environmental conditions allowing users to walk without feeling exhausted. The methodology was tested on an open area and an urban canyon in Milan; applicability by urban designers was key in developing a simplified way to evaluate shading needs. This approach could be applied to evaluate solar radiation exposure of pedestrian paths adopting diverse user experiences as an evaluation criterion. [ABSTRACT FROM AUTHOR]

The faster a drug enters the brain, the greater its addictive potential, yet the brain circuits underlying the rate dependency to drug reward remain unresolved. With simultaneous PET-fMRI we linked dynamics of dopamine signaling, brain activity/connectivity, and self-reported 'high' in 20 adults receiving methylphenidate orally (results in slow delivery) and intravenously (results in fast delivery) (trial NCT03326245). We estimated speed of striatal dopamine increases to oral and IV methylphenidate and then tested where brain activity was associated with slow and fast dopamine dynamics (primary endpoint). We then tested whether these brain circuits were temporally associated with individual 'high' ratings to methylphenidate (secondary endpoint). A corticostriatal circuit comprising the dorsal anterior cingulate cortex and insula and their connections with dorsal caudate was activated by fast (but not slow) dopamine increases and paralleled 'high' ratings. These data provide evidence in humans for a link between dACC/insula activation and fast but not slow dopamine increases and document a critical role of the salience network in drug reward. The faster a drug enters the brain, the greater its addictive potential. Using simultaneous PET-fMRI in humans, here the authors report a neural circuit responding to fast but not slow dopamine increases from intravenous versus oral methylphenidate delivery. [ABSTRACT FROM AUTHOR]

Background: A novel ablation catheter has been released to map and ablate the cavo-tricuspid isthmus (CTI) in patients with atrial flutter (AFL), improving ablation efficiency. Methods: We evaluated the acute and long-term outcome of CTI ablation aiming at bidirectional conduction block (BDB) in a prospective, multicenter cohort study enrolling 500 patients indicated for typical AFL ablation. Patients were grouped on the basis of the AFL ablation method (linear anatomical approach, Conv group n = 425, or maximum voltage guided, MVG group, n = 75) and ablation catheter (mini-electrodes technology, MiFi group, n = 254, or a standard 8-mm ablation catheter, BLZ group, n = 246). Results: Complete BDB according to both validation criteria (sequential detailed activation mapping or mapping only the ablation site) was achieved in 443 patients (88.6%). The number of RF applications needed to achieve BDB was lower in the MiFi MVG group vs both the MiFi Conv group and the BLZ Conv group (3.2 ± 2 vs 5.2 ± 4 vs 9.3 ± 5, p < 0.0001 for all comparisons). Fluoroscopy time was similar among groups, whereas we observed a reduction in the procedure duration from the BLZ Conv group (61.9 ± 26min) to the MiFi MVG group (50.6 ± 17min, p = 0.048). During a mean follow-up of 548 ± 304 days, 32 (6.2%) patients suffered an AFL recurrence. No differences were found according to BDB achieved by both validation criteria. Conclusions: Ablation was highly effective in achieving acute CTI BDB and long-term arrhythmia freedom irrespective of the ablation strategy or the validation criteria for CTI chosen by the operator. The use of an ablation catheter equipped with mini-electrodes technology seems to improve ablation efficiency. Clinical trial registration: Atrial Flutter Ablation in a Real World Population. (LEONARDO). ClinicalTrials.gov Identifier: NCT02591875 [ABSTRACT FROM AUTHOR]

Radiative corrections for elementary processes as elastic electron-proton scattering and electron-positron annihilation into proton-antiproton (and the time reverse reaction) are discussed. The knowledge of hadron characteristics as electromagnetic form factors heavily depends on the radiative corrections applied to the experimental observables and on the assumed reaction mechanism. A compared analysis of scattering and annihilation reactions, on the basis of fundamental symmetries, allows to formulate model independent statements that are a necessary guide for model calculations. [ABSTRACT FROM AUTHOR]

From the Pioneer Era of the aviation to World War I the evolution of aircraft technology and chemical synthesis enabled a unique coexistence of traditional craftsmanship, artistic decoration practices, and technological advancements. The study of the materials used in these early years of aviation is still an uncharted territory: a vast portion of remaining planes has been partially or completely repaired and restored, usually by total replacement of the fabric. The Italian biplane Ansaldo A.1 (1918) is a fighter aircraft and is one of the few planes in the world that still preserves its own original materials. In the last years, the fabric sections of the airplane have started to become brittle and loose cohesion, severely compromising the integrity of the aircraft, and resulting in a general alteration of the pictorial layers of the painted sections. A chemical investigation was undertaken to unveil the materials, and to elucidate the causes of the degradation. This study presents one of the first steps into the study of early historical aircrafts, defining the background for the conservation plans to preserve these objects for future generations. [ABSTRACT FROM AUTHOR]

This paper compares the performance of probabilistic and deterministic capacity models for reinforced timber members under compression perpendicular to the grain. A database collecting approximately 60 test results has been compiled by reviewing research papers and master's and doctoral theses from the past twenty years. The capacity model proposed for the next generation of Eurocodes assesses the capacity as the minimum between the values associated with two failure modes, one at the contact plate and one at the screw tips. The main drawbacks of the model are the excessive elaborateness, given its limitation in accuracy and the fallacy in predicting the observed failure modes. In detail, the failure by the screw tips seldom occurs, although it was expected in more than half of the selected specimens. The authors attempted to simplify the capacity equation by proposing a generalized expression corresponding to the failure mode at the contact plate, corrected by a factor including the effects of load and screw arrangement and geometric details of the specimen. A deterministic mechanical model obtained by multiplying the timber strength by the contact area with a given coefficient performs better than the Eurocode model, which attempts to include the effect of load diffusion (R 2 ≈ 0.27 ). A constant factor equal to 2 yields a suitable fitting (R 2 ≈ 0.76 ). The best performance is achieved with a four-term polynomial, with adimensional addends, leading to an optimum fitting (R 2 ≈ 0.82 ). [ABSTRACT FROM AUTHOR]

Purpose: Heart rate variability (HRV) estimates the autonomic nervous system (ANS) influence on the heart and appears sex-specific. Sensory afferents exhibit sex-specificity; although, it is unknown if Capsaicin, an agonist for transient receptor potential vanilloid channel-1 (TRPV1), alters cardiac ANS activity in a sex-dependent manner, which could be important given the predictive nature of HRV on risk of developing hypertension. Thus, we explored if there was sex-specificity in the effect of capsaicin on estimated cardiac ANS activity. Methods: HRV was measured in 38 young males (M: n = 25) and females (F: n = 13), in a blinded-crossover design, after acute ingestion of placebo or capsaicin. Resting HR, RR-interval, root-mean-square of successive differences (RMSSD), natural log-transformed RMSSD (LnRMSSD), standard deviation of n–n intervals (SDNN), number of pairs of successive n–n intervals differing by > 50 ms (NN50), and percent NN50 (PNN50) were obtained using standard techniques. Results: Significant sex differences were observed in mean HR (M: 59 ± 9.3 vs. F: 65 ± 12 beats/min, p = 0.036, η2 = 0.098), minimum HR (M: 47 ± 8.3 vs. F: 56 ± 12 beats/min, p = 0.014, η2 = 0.124), and NN50 (M: 177 ± 143 vs. F: 29 ± 17, p < 0.001, η2 = 0.249). There was a significant interaction of sex*treatment (p = 0.02, η2 = 0.027) for RMSSD, where males increased (78 ± 55 vs. 91 ± 64 ms), and females decreased (105 ± 83 vs. 76 ± 43 ms), placebo vs. capsaicin. Conclusion: This controlled study recapitulates sex differences in HR and HRV, but revealed a sexual dimorphism in the parasympathetic response to capsaicin, perhaps due to differing TRPV1-afferent sensitivity, highlighting a potential mechanism for differential regulation of hemodynamics, and CVD risk, and should be considered in future studies. [ABSTRACT FROM AUTHOR]

The acceleration of pozzolanic reactions, via increasing curing temperature, has practical applications for soil stabilization at geotechnical sites (e.g. pavement layers). In this context, this research aims the following: to evaluate the influence of curing temperature (23°C and 40°C) on a fibre reinforced Osorio sand mixed with fly ash, lime and sodium chloride (NaCl) by measuring freezing and thawing cycles, stiffness and unconfined compressive strength; to determine statistically the influence of lime content, NaCl, polypropylene fibres and dry unit weight (γd) over the measured response variable for both curing temperatures; and to expand pavement design methodologies by correlating durability, strength and stiffness with the porosity/binder index [η/(Biv)0.28]. Regardless of curing temperature the specimen stiffness presented a typical behavior: fibres decreased the mixture stiffness while NaCl increased it. For mixtures without fibres the rupture was brittle, while mixtures with fibres had ductile rupture. Statistical analysis showed that increased compaction (γd of 14kN/m3, 15kN/m3 and 16kN/m3) improved all response variables (unconfined compression strength, stiffness at slight strain modulus and freeze–thaw durability). However, better results were achieved with the temperature increment in the curing process. [ABSTRACT FROM AUTHOR]

Noninvasive estimation of joint loads is still an open challenge in biomechanics. Although musculoskeletal modeling represents a solid resource, multiple improvements are still necessary to obtain accurate predictions of joint loads and to translate such potential into practical utility. The present study, focused on the hip joint, is aimed at reviewing the state-of-the-art literature on the estimation of hip joint reaction forces through musculoskeletal modeling. Our literature inspection, based on well-defined selection criteria, returned seventeen works, which were compared in terms of methods and results. Deviations between predicted and in vivo measured hip joint loads, taken from the OrthoLoad database, were assessed through quantitative deviation indices. Despite the numerous modeling and computational improvements made over the last two decades, predicted hip joint loads still deviate from their experimental counterparts and typically overestimate them. Several critical aspects have emerged that affect muscle force estimation, hence joint loads. Among them, the physical fidelity of the musculoskeletal model, with its parameters and geometry, plays a crucial role. Also, predicted joint loads are markedly affected by the selected muscle recruitment strategy, which reflects the underlying motor control policy. Practical guidelines for researchers interested in noninvasive estimation of hip joint loads are also provided. [ABSTRACT FROM AUTHOR]

The wide use of copper (Cu)-based fungicide has caused a stepwise accumulation of Cu in the environment increasing the occurrence of phytotoxicity in crops. To understand and alleviate this abiotic stress, maize seedlings were grown in hydroponic solution with different combinations of Cu and iron (Fe) forms. Results showed that maize Cu sensitivity is related to the nature of the form supplied and to the chelate-exchange processes that might involve other elements, such as Fe. The use of CuSO4 excess (100 µM) caused severe reduction of plant growth, over accumulation of Cu, high activity of antioxidant enzymes, and impairment of the acquisition of other nutrients. In presence of chelating agents (citrate and ethylenediaminetetraacetic acid, EDTA) the ability of plants to tolerate high Cu-levels depends on the Fe nutritional status. Copper phytotoxicity symptoms do not occur when Cu was supplied chelated by EDTA. The use of synthetic agent EDTA (as Cu-EDTA and Fe-EDTA) prevented the accumulation of toxic Cu-level in plants and allowed a better homeostasis among nutrients. In presence of citrate, high concentration of Cu occurred in plants but its phytotoxicity was limited when even EDTA was available in solution. Results suggest that maize plants can operate a good control of nutritional status when Cu-excess is present concomitantly with a synthetic chelator (as EDTA) even when supplied as a Fe-fertilizer. These results pave the way to provide guidelines for the fertilization managements on Cu-contaminated soils to alleviate phytotoxicity in crops. [ABSTRACT FROM AUTHOR]

Dopamine facilitates cognition and is implicated in reward processing. Methylphenidate, a dopamine transporter blocker widely used to treat attention-deficit/hyperactivity disorder, can have rewarding and addictive effects if injected. Since methylphenidate's brain uptake is much faster after intravenous than oral intake, we hypothesize that the speed of dopamine increases in the striatum in addition to its amplitude underly drug reward. To test this we use simulations and PET data of [11C]raclopride's binding displacement with oral and intravenous methylphenidate challenges in 20 healthy controls. Simulations suggest that the time-varying difference in standardized uptake value ratios for [11C]raclopride between placebo and methylphenidate conditions is a proxy for the time-varying dopamine increases induced by methylphenidate. Here we show that the dopamine increase induced by intravenous methylphenidate (0.25 mg/kg) in the striatum is significantly faster than that by oral methylphenidate (60 mg), and its time-to-peak is strongly associated with the intensity of the self-report of "high". We show for the first time that the "high" is associated with the fast dopamine increases induced by methylphenidate. Combined PET imaging and mathematical simulations reveal that the rate of dopamine increase in the striatum underlies self-reports of drug "high" in response to oral and intravenous methylphenidate challenges in humans [ABSTRACT FROM AUTHOR]

Background: The second-generation cryoballoon (CB) has proven to be a highly effective ablative strategy in patients with symptomatic atrial fibrillation (AF). This study sought to investigate the anatomical characteristics of pulmonary veins (PVs) and the relationship between their size, ovality, and late reconnections in a large cohort of patients undergoing repeat ablation for recurrence of atrial arrhythmias. Methods and results: A total of 152 consecutive patients (98 males, 64.5%; mean age 64.9 ± 9.6 years) underwent a repeat ablation for recurrent atrial tachyarrhythmias after a median time of 6.5 months [IQR 11] from the index CB ablation. All repeat ablations were performed using a 3-dimensional electro-anatomical mapping system. Among all 593 PVs, 134 (22.6%) showed a late PV reconnection in 95 patients (0.88 per patient), at the time of repeat ablation procedure. There was a significant difference in ovality between left- and right-sided PVs (p < 0.001). Greater diameters of left superior PV, left inferior PV, and right inferior PV ostia (both maximum and minimum) and higher index ovality were significantly associated with late PV reconnection. Conclusions: The rate of late PV reconnection after CB ablation was low (0.88 PVs/patient). Left-sided PVs were more oval than septal PVs. Larger PV dimensions and higher ovality index were significantly associated with reconnections in all PVs except for RSPV. [ABSTRACT FROM AUTHOR]

Aims: The prevention of pulmonary toxicity is an important goal for patient candidate to radiation therapy for lung cancer. There is a lack of evidence on the role of exercise training for patients with unresectable stage III lung cancer candidated to radical treatment. The aim of this study was to evaluate the feasibility of a home-based pulmonary rehabilitation (PR) program and to identify reliable tools in terms of respiratory function, exercise capacity and quality of life. Methods: Patients' recruitment lasted from April 2020 till February 2022. The PR program was proposed concomitantly to radiation therapy to the first 20 patients (interventional group, IG), and the other 20 patients were identified as an observational group (OG). All patients were assessed at baseline (T0) and after 8 weeks (T2) with 6 minute walking test (6MWT), modified Borg Scale (mBORG), SF-36 questionnaire (SF-36) and pulmonary function test (PFT); after 4 weeks (T1), only SF-36 was administered. Results: A decrease of 13.8 m in the walked-distance was registered in the OG between T0 and T2 (p = 0.083). Instead, an increase of 56.6 m in the distance walked was recorded in the IG between T0 and T2 (p ≤ 0.001). In the OG, the mBORG scores showed a negative trend. On the contrary, in the IG, these scores showed a slight improvement. In the OG, all the items of SF-36 scores decreased between T0 and T1. In the IG, an increased trend from T0 to T2 was observed for all the items of SF-36. No clinically significant variations were detected from baseline to T2 in both groups regarding PFT. Conclusion: The 6MWT, mBORG and SF-36 resulted as useful tools to assess the role of a PR program. A significant gain in functional exercise capacity and a prevention of the physiological impairment of QoL during radio(chemo)therapy was registered. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is associated with systemic toxicity, represented by changes in biomarkers associated with mood episodes, leading to neurological damage, which may reflect cognitive functions and functionality and the progression of the disease. We aimed to analyze the effect of four biomarkers, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and thiobarbituric acid reactive substances (TBA-RS), related to oxidative stress in BD and to correlate them with cognitive functions and functionality. We studied 50 bipolar types I/II patients in the euthymic phase, which was divided into two subgroups with 25 patients each (≤ 3 years and ≥ 10 years of diagnosis, from the first episode of mania) and 25 control patients. To analyze frontal cognitive functions and functionality, we used the Frontal Assessment Battery (FAB) and Functioning Assessment Short Test (FAST) tests, respectively. The scores of the FAST and FAB tests showed an increase and decrease respectively, in both bipolar groups, when compared to the control group, demonstrating impairment in cognitive functions and functionality since the disease onset. In addition, changes occurred in all six domains of the FAST test, and in four domains of the FAB test in bipolar patients when compared to the control group. Regarding oxidative stress biomarkers, we did not find changes in SOD and GSH-Px activities; however, a significant increase in CAT activity and lipid peroxidation was observed in both groups, although the patients were euthymic and medicated. These results allow us to raise the hypothesis that since the beginning of the disease, the euthymic bipolar patient has presented a level of oxidative stress, which gets worse with the evolution of the disease, promoting impairments in the frontal cognitive functions and functionality gradually. [ABSTRACT FROM AUTHOR]

The prevalent use of Li-ion batteries (LIBs) has risen concern about the health hazard they might induce with regard to some of their toxic constituents. Beside chemical safety aspects, the occurrence of performance-enhanced electrodes made of composite materials containing microparticles and nanoparticles is another point to be considered with regard to occupational and user exposure to airborne (nano)particles (NPs) potentially emitted during the life cycle of LIBs. In this study, we investigated the emission of airborne particles during combustion in air at 850 °C (mimicking an accidental scenario of defective devices) and during pyrolysis in nitrogen gas at 1000 °C (mimicking end-of-life treatment) of fresh and aged composite anodes containing Si and Si@C NPs. Cycling of the cells resulted in the loss of surface integrity of the anode active layer and in the partial fusion of the Si-based NPs with a sixfold to eightfold increase in size. Such alteration induced fivefold to tenfold higher levels of particles released by aged anodes compared to fresh ones, with a shift towards larger population sizes, both in combustion and pyrolysis assays. Combustion was 10 to 30 times less emissive than pyrolysis, due to the better completion of the carbon matrix degradation with oxygen. The only significant difference in emission between the Si-based composite anodes and the reference anodes (without Si NPs) was observed with aged anodes during pyrolysis assays (10- to 20-fold increase). From a nanosafety aspect, this point should be mitigated given the size of the emitted particles. [ABSTRACT FROM AUTHOR]

Purpose: Real-world safety data on the use of transcatheter pacing systems particularly in very elderly patients is still limited. The aim of this analysis was to investigate the effect of age on the safety and efficacy of leadless pacemaker implant. Methods: From May 2016 through July 2019, 577 patients were implanted with a leadless single-chamber pacemaker according to current pacing indication in 15 Italian cardiologic centers. The population was divided into age quartiles for evaluation, including (1) < 70 years, (2) 70–77 years, (3) 78–83 years, and (4) ≥ 83 years. Procedural data, complications, and electrical parameters were collected at baseline and during the follow-up. Results: Procedural-related complication occurrence was very low (< 1.0%) and similar in the four subgroups according to age even if the older patients were more frail. No cardiac tamponade was reported. Among the groups, no difference was observed in procedural time, fluoroscopy time duration, and electrical parameters (mean pacing impedance: 750 ± 192 and 599 ± 156, mean pacing threshold: 0.7 ± 0.5 and 0.7 ± 0.6, and mean right ventricular sensing 10.7 ± 6.1 and 11.5 ± 4.8 at implant and last follow-up, respectively). Conclusions: The reported data demonstrated a high degree of safety during leadless implant across all patient ages. Procedural complications and device electrical measurements were similar among the different ages. [ABSTRACT FROM AUTHOR]

The ovarian tumor microenvironment (TME) is characterized by the accumulation of immunosuppressive tumor-associated macrophages (TAMs) and granulocytic cells. Very small size particles (VSSP), comprised of the ganglioside NAcGM3 and Neisseria meningitidis derived outer membrane vesicles, is being developed as a nanoparticulated modulator of innate immunity. Prior studies have shown that VSSP enhanced antigen-specific cytotoxic T cell responses and reduced the suppressive phenotype of splenic granulocytic cells in tumor-bearing mice. Here, we hypothesized that intraperitoneal VSSP would modify myeloid cell accumulation and phenotypes in the ovarian TME and abrogate suppressor function of TAMs and tumor-associated granulocytic cells. In the ID8 syngeneic model of epithelial ovarian cancer, VSSP reduced peritoneal TAMs and induced M1-like polarization in TAMs. In addition, VSSP stimulated peritoneal inflammation characterized by increased granulocytes and monocytes, including inflammatory monocytic cells. VSSP treatment resulted in peritoneal TAMs and granulocytic cells being less suppressive of ex vivo stimulated CD8+ T cell responses. VSSP alone and combined with anti-PD-1 modestly but significantly prolonged survival in tumor-bearing mice. In addition, ex vivo treatment with VSSP induced M1-like polarization in TAMs from patients with metastatic ovarian cancer and variably abrogated their suppressor phenotype. VSSP treatment also partially abrogated the induction of suppressor function in healthy donor neutrophils exposed to ascites supernatants from patients with ovarian cancer. Together, these results point to VSSP reprogramming myeloid responses resulting in abrogation of suppressive pathways and raise the potential for administration of VSSP into the TME to enhance anti-tumor immunity. [ABSTRACT FROM AUTHOR]

Eye-blink rate has been proposed as a biomarker of the brain dopamine system, however, findings have not been consistent. This study assessed the relationship between blink rates, measured after oral placebo) (PL) and after a challenge with oral methylphenidate (MP; 60 mg) and striatal D1 receptor (D1R) (measured at baseline) and D2 receptor (D2R) availability (measured after PL and after MP) in healthy participants. PET measures of baseline D1R ([11C]NNC112) (BL-D1R) and D2R availability ([11C]raclopride) after PL (PL-D2R) and after MP (MP-D2R) were quantified in the striatum as non-displaceable binding potential. MP reduced the number of blinks and increased the time participants kept their eyes open. Correlations with dopamine receptors were only significant for the eye blink measures obtained after MP; being positive for BL-D1R in putamen and MP-D2R in caudate (PL-D2R were not significant). MP-induced changes in blink rates (PL minus MP) were negatively correlated with BL-D1R in caudate and putamen. Our findings suggest that eye blink measures obtained while stressing the dopamine system might provide a more sensitive behavioral biomarker of striatal D1R or D2R in healthy volunteers than that obtained at baseline or after placebo. PET imaging in human participants revealed that D1 and D2 dopamine receptor availability was associated with eye-blink rates following treatment with oral methylphenidate, but not a placebo. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) commonly affects older patients; however, several studies have documented an increase in its incidence among younger patients. Therefore, it is important to investigate if this trend is also found in different geographic regions. The pathology files of diagnostic and therapeutic institutions from different parts of the globe were searched for OSCC cases diagnosed from 1998 to 2018. Data regarding the sex, age, and tumor location of all cases, as well as the histologic grade and history of exposure to risk habits of cases diagnosed as OSCC in young patients (≤ 40 years of age) were obtained. The Chi-square test was used to determine any increasing trend. A total of 10,727 OSCC cases were identified, of which 626 cases affected young patients (5.8%). Manipal institution (India) showed the highest number of young patients (13.2%). Males were the most affected in both age groups, with the tongue and floor of the mouth being the most affected subsites. OSCC in young individuals were usually graded as well or moderately differentiated. Only 0.9% of the cases occurred in young patients without a reported risk habit. There was no increasing trend in the institutions and the period investigated (p > 0.05), but a decreasing trend was observed in Hong Kong and the sample as a whole (p < 0.001). In conclusion there was no increase of OSCC in young patients in the institutions investigated and young white females not exposed to any known risk factor represented a rare group of patients affected by OSCC. [ABSTRACT FROM AUTHOR]