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Purpose: To assess the impact of neoadjuvant and adjuvant chemotherapy on survival outcomes, within a large multicenter cohort of Upper tract urothelial carcinoma patients treated with Nephroureterectomy. Methods: A multicenter retrospective analysis utilizing the Robotic surgery for Upper Tract Urothelial Cancer Study registry was performed. Baseline, preoperative, perioperative, and pathologic variables of three groups of patients receiving surgery only, neoadjuvant or adjuvant chemotherapy were compared. Categorical and continuous variables among the three subgroups were compared with Chi square and ANOVA tests. The impact of perioperative chemotherapy on survival outcomes was assessed with the Kaplan Meier method. Univariable and multivariable Cox regression analyses were performed to identify predictors of survival. Results: Overall, 1,994 patients were included. Overall and Clavien grade ≥3 complications rates were comparable among the three subgroups (p = 0.65 and p = 0.92). At Kaplan Meier analysis, neoadjuvant chemotherapy significantly improved cancer-specific survival (p = 0.03) and overall survival (p = 0.03) probabilities of patients with cT ≥ 3 tumors and of those with positive cN (p = 0.03 and p = 0.02). On multivariable analysis, neoadjuvant chemotherapy was independently associated with an improvement of cancer-specific survival in cT ≥ 3 patients (HR 0.44; p = 0.04), and of both cancer-specific survival (HR 0.50; p = 0.03) and overall survival (HR 0.53; p = 0.02) probabilities in positive cN patients. Conclusions: This large multicenter retrospective analysis suggests significant survival benefit in Upper tract urothelial carcinoma patients with either locally advanced or clinically positive nodes disease receiving neoadjuvant chemotherapy. These findings can be regarded as "hypothesis generating", stimulating future trials focusing on such advanced stages. [ABSTRACT FROM AUTHOR]

The "Left Perceptual Bias" (LPB) is the effect for which the left side of a picture such as a face is used to a greater extent than its right side as shown in a wide variety of experimental tasks. This effect has been observed for faces, body parts and objects. The present work investigated the presence of a LPB in recognizing hand gestures in two experiments. The role of the side of stimuli presentation (left /right), stimuli orientation (palm/back), participants' handedness and gender were analyzed. Participants were presented with images of meaningless gestures performed by an actor with the right or left hand, from a palm or a back view. Immediately afterward, participants were shown a drawing and had to discriminate whether it represented the same gesture or not. In the first experiment, the task was administered to a sample of right-handed participants, half males. Results showed shorter response times for stimuli presented on the left side and for those shown from the palm. No gender differences were observed. The second experiment included a sample of left-handed participants and the LPB was replicated. Taken together, our results suggest an interpretation of the bias in terms of asymmetries in perceptual processing rather than the involvement of motor representations. [ABSTRACT FROM AUTHOR]

Background: The mechanisms at the basis of depression are still matter of debate, but several studies in the literature suggest common pathways with dementia (genetic predispositions, metabolic and inflammatory mechanisms, neuropathological changes) and other geriatric syndromes. Aims: To evaluate the role of cortisol (as marker of the HPA, hypothalamus–pituitary–adrenal axis hyperactivity) in elderly subjects with depressive symptoms (by the means of the AGICO, AGIng and COrtisol, study), in relationship to the presence of the major geriatric syndromes. Methods: The AGICO study enrolled patients from ten Geriatric Units in Italy. Every subject received a comprehensive geriatric assessment or CGA (including the Mini Mental State Examination or MMSE, Geriatric Depression Scale or GDS and Cornell Scale for Depression in Dementia or CSDD), the neurological examination (with a computed tomography scan or magnetic resonance imaging of the brain), the assessment of the metabolic syndrome (MetS), the evaluation of the cortisol activity by two consecutive urine collections (diurnal and nocturnal), a CGA-derived frailty index (FI) and a modified measure of allostatic load (AL). Results: The MMSE scores were significantly and inversely related to the values of GDS (p < 0.001) and CSDD (p < 0.05), respectively. The patients with depressive symptoms (GDS/CSDD > 8) showed significantly increased disability, MetS, inflammation, FI and AL and significantly reduced MMSE and renal function. The diurnal and nocturnal urinary cortisol levels in the patients with depressive symptoms (GDS/CSDD > 8) were higher with respects to controls (p < 0.05 for nocturnal difference). Discussion: The AGICO study showed that the stress response is activated in the patients with depression. Conclusion: The depression in elderly patient should be reconsidered as a systemic disease, with coexisting major geriatric syndromes (disability, dementia, frailty) and combined pathogenetic mechanisms (metabolic syndrome, impaired renal function, low-grade inflammation, and allostatic load). Cortisol confirmed its role as principal mediator of the aging process in both dementia and metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background: Clinical prediction models (CPM), such as the SCOAP-CERTAIN tool, can be utilized to enhance decision-making for lumbar spinal fusion surgery by providing quantitative estimates of outcomes, aiding surgeons in assessing potential benefits and risks for each individual patient. External validation is crucial in CPM to assess generalizability beyond the initial dataset. This ensures performance in diverse populations, reliability and real-world applicability of the results. Therefore, we externally validated the tool for predictability of improvement in oswestry disability index (ODI), back and leg pain (BP, LP). Methods: Prospective and retrospective data from multicenter registry was obtained. As outcome measure minimum clinically important change was chosen for ODI with ≥ 15-point and ≥ 2-point reduction for numeric rating scales (NRS) for BP and LP 12 months after lumbar fusion for degenerative disease. We externally validate this tool by calculating discrimination and calibration metrics such as intercept, slope, Brier Score, expected/observed ratio, Hosmer–Lemeshow (HL), AUC, sensitivity and specificity. Results: We included 1115 patients, average age 60.8 ± 12.5 years. For 12-month ODI, area-under-the-curve (AUC) was 0.70, the calibration intercept and slope were 1.01 and 0.84, respectively. For NRS BP, AUC was 0.72, with calibration intercept of 0.97 and slope of 0.87. For NRS LP, AUC was 0.70, with calibration intercept of 0.04 and slope of 0.72. Sensitivity ranged from 0.63 to 0.96, while specificity ranged from 0.15 to 0.68. Lack of fit was found for all three models based on HL testing. Conclusions: Utilizing data from a multinational registry, we externally validate the SCOAP-CERTAIN prediction tool. The model demonstrated fair discrimination and calibration of predicted probabilities, necessitating caution in applying it in clinical practice. We suggest that future CPMs focus on predicting longer-term prognosis for this patient population, emphasizing the significance of robust calibration and thorough reporting. [ABSTRACT FROM AUTHOR]

Purpose: To investigate Health Related Quality of Life (HRQoL) features of long survivors after radical cystectomy (RC) compared to healthy population (HP) control. Methods: Patients with cT2-4/N0/M0 or Bacillus Calmette-Guérine (BCG) failure high-grade non-muscle-invasive bladder cancer (NMIBC) undergoing RC and ileal Orthotopic Neobladder (iON) from 2010 to 2015 were enrolled in "BCa cohort". Patients aged ≥ 18 yrs old, with no previous diagnosis of BCa or any genitourinary cancer disease were included from General Practitioner outpatients and enrolled in "HP cohort". A 1:1 propensity score matched (PSM) analysis was performed, and HRQoL outcomes were collected according to European Organization for Research and Treatment of Cancer (EORTC), and generic (QLQ-C30) questionnaires. Results: A total of 401 patients were enrolled in the study, 99 and 302 in BCa and HP cohorts, respectively. After applying 1:1 PSM analysis 67 patients were included for each group. Analysis of self-reported HRQoL outcomes described a better HRQoL in BCa cohort. Particularly, in the long run patients receiving RC and iON significantly experienced higher global health-status/QoL (p < 0.001), emotional (p = 0.003) and cognitive functioning (p < 0.001) than HP cohort, providing a significantly lower impairment in terms of fatigue (p = 0.004), pain (p = 0.004), dyspnea (p = 0.02) and insomnia (p = 0.005). Conclusions: Long survivors after RC and iON seems to have a major awareness of self-reported HRQoL compared to HP control group. [ABSTRACT FROM AUTHOR]

Purpose: Aim of this study is to investigate the association between DM and oncological outcomes among patients with muscle-invasive (MI) or high-risk non-muscle invasive (NMI) bladder cancer (BC) who underwent robot-assisted radical cystectomy with intracorporeal urinary diversion (RARC). Methods: An IRB approved multi-institutional BC database was queried, including patients underwent RARC between January 2013 and June 2023. Patients were divided into two groups according to DM status. Baseline, clinical, perioperative, pathologic data were compared. Chi-square and Student t tests were performed to compare categorical and continuous variables, respectively. Kaplan-Meier method and Cox regression analyses were performed to assess the association between DM and oncologic outcomes. Results: Out of 547 consecutive patients, 97 (17.7%) had DM. The two cohorts showed similar preoperative features, except for ASA score (p = 0.01) and Hypertension rates (p < 0.001). No differences were detected for perioperative complications, pT stage, pN stages and surgical margins status (all p > 0.12). DM patients displayed significantly lower 5-yr disease-free survival (DFS) (44.6% vs. 63.3%, p = 0.007), 5-yr cancer-specific survival (CSS) (45.1% vs. 70.1%, p = 0.001) and 5-yr Overall survival (OS) (39.9% vs. 63.8%, p = 0.001). At Multivariable Cox-regression analyses DM status was identified as independent predictor of worse cancer-specific survival (CSS) (HR 2.1; p = 0.001) and overall survival (OS) (HR 2.05; p < 0.001). Conclusion: Among BC patients who underwent RARC, DM patients showed worse oncologic outcomes than the non-DM patients, with DM status playing an independent negative predicting role in CSS and OS. Future prospective studies are awaited, stimulating basic and translational research to identify possible mechanisms of interaction between DM and BC. [ABSTRACT FROM AUTHOR]

Introduction: The need for a standardized core curriculum in regional anesthesia has become essential, particularly with the integration of ultrasound revolutionizing and exponentially increasing clinical practice and possibilities. In fact, numerous novel techniques, often overlapping, can confuse practitioners. This study aims to establish a core curriculum for upper limb, lower limb, paraspinal and fascial plane blocks for residency training, addressing potential educational gaps caused by the multitude of techniques, through a Delphi consensus process involving recognized Italian regional anesthesia experts. Methods: A steering committee was formed in order to select a panel of experts in regional anesthesia. A three-round Delphi consensus was planned: two rounds of electronic voting and a final round of mixed electronic voting and round table discussion. The consensus was defined as ≥ 75% agreement for inclusion and lower than ≤ 25% agreement for exclusion from the core curriculum list. Techniques reaching the 50% threshold were included with low consensus. Results: Twenty-nine techniques were selected to be included in the ultrasound-guided regional anesthesia core curriculum. Twenty-two were included with strong consensus: Upper limb: interscalene brachial plexus block, supraclavicular brachial plexus block, infraclavicular brachial plexus block, axillary brachial plexus block, intermediate cervical plexus block Lower limb: femoral nerve block, pericapsular nerve group block, adductor canal block, sciatic nerve block (transgluteal approach, infragluteal approach, and at the popliteal fossa), ankle block Paraspinal/fascial plane blocks: erector spinae plane block, deep serratus anterior plane block, superficial pectointercostal plane block, interpectoral plane block, pectoserratus plane block, rectus sheath block, ilioinguinal iliohypogastric nerves block, transversus abdominis plane block (with subcostal and midaxillary approaches) The remaining seven techniques were included with low consensus: superficial cervical plexus block, lumbar plexus block, fascia iliaca block (suprainguinal approach), anterior quadratus lumborum block, lateral quadratus lumborum block, paravertebral block, and serratus anterior plane block. Conclusions: This curriculum aims to standardize training and ensure that residents acquire the essential skills required for effective and safe practice regardless of the residents' subsequent specialization. By incorporating these techniques, educational programs can provide a structured and consistent approach to regional anesthesia, enhancing the quality of patient care and improving outcomes. [ABSTRACT FROM AUTHOR]

In the study of biological populations, the Allee effect detects a critical density below which the population is severely endangered and at risk of extinction. This effect supersedes the classical logistic model, in which low densities are favorable due to lack of competition, and includes situations related to deficit of genetic pools, inbreeding depression, mate limitations, unavailability of collaborative strategies due to lack of conspecifics, etc. The goal of this paper is to provide a detailed mathematical analysis of the Allee effect. After recalling the ordinary differential equation related to the Allee effect, we will consider the situation of a diffusive population. The dispersal of this population is quite general and can include the classical Brownian motion, as well as a Lévy flight pattern, and also a “mixed” situation in which some individuals perform classical random walks and others adopt Lévy flights (which is also a case observed in nature). We study the existence and nonexistence of stationary solutions, which are an indication of the survival chance of a population at the equilibrium. We also analyze the associated evolution problem, in view of monotonicity in time of the total population, energy consideration, and long-time asymptotics. Furthermore, we also consider the case of an “inverse” Allee effect, in which low density populations may access additional benefits. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, including alteration in emotional processing and recognition of emotions. We explored the effects of PD on the emotional behavioral ratings using a battery of affective visual stimuli selected from the International Affective Picture System (IAPS). Methods: Twenty-two patients diagnosed with idiopathic PD and 22 healthy controls (HC), matched by age, gender, and education, were enrolled in the study. Following a clinical assessment, each participant was asked to evaluate the arousal and valence of affective visual stimuli, and response time was recorded. Disease-specific measures including the MDS Unified Parkinson's Disease Rating Scale (MDS UPDRS) and the Non-Motor Symptom Scale (NMSS) were also collected. Results: PD patients exhibited higher arousal responses compared to HC for negative/unpleasant pictures (scoring 7.32 ± 0.88 vs 5.43 ± 2.06, p < 0.001). The arousal response to negative/unpleasant pictures was correlated with measures of non-motor burden in PD (MDS UPDRS I and NMSS, rho = 0.480 and p = 0.023, rho = 0.533 and p = 0.010, respectively). Conclusion: Impaired emotional processing characterizes PD patients with mild disease and is related to the non-motor symptom burden. Given the importance of emotional processing for the development and maintenance of close interpersonal relationship and for coping with specific medical situations, it is crucial to direct PD patients towards therapeutic interventions focused on the recognition and processing of emotions. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the incidence of postoperative complications after cytoreductive nephrectomy (CN) following first-line treatment for metastatic renal cell carcinoma (mRCC), and to compare it with postoperative complications of upfront CN. Methods: For this population-based retrospective study, the PearlDiver Mariner database (PearlDiver Technologies, Colorado Springs, CO), a database of insurance billing records was analyzed. Using relevant ICD-9/10 and CPT codes, patients diagnosed with mRCC between 2011 and 2021, who received first-line systemic molecular therapy (SMT), either tyrosine kinase inhibitors (TKI) or immune-checkpoint inhibitors (ICI), were identified. The selected population was stratified into two cohorts according to the timing of CN (deferred: after SMT vs. upfront: before SMT). Propensity-score matching (PSM) was performed as per baseline patients' characteristics to control for potential confounders between the two cohorts. The primary outcome was to compare 30-day postoperative complications rate between patients undergoing upfront vs. deferred CN. Results: After PSM, 162 patients who received upfront CN were compared with 162 patients who underwent deferred CN. The overall rate of 30-day postoperative complications was statistically significantly higher in patients undergoing deferred CN (33.9%), compared to patients treated with upfront CN (21%, p < 0.01). In addition, the rate of both medical (26.5% vs. 14.2%, p < 0.01) and surgical (14.8 vs. 7.4%, p = 0.03) complication rate was statistically significantly higher in deferred vs. upfront CN. Multivariable logistic regression analysis revealed that none of the treatment regimens significantly predicted the occurrence of postoperative complications. Conclusion: Patients undergoing deferred CN experience a higher rates of overall, medical, and surgical 30-day postoperative complications compared to those receiving upfront surgery. Findings from this study should be interpreted within the limitations of this type of analysis. [ABSTRACT FROM AUTHOR]

In vitro propagation, is becoming the predominant method for blackberry propagation due to its advantages compared to agamic traditional propagation methods. Synthetic seed technology represents a promising approach to further enhance the productivity of in vitro propagation facilitating the exchange of plant materials among laboratories and contributing to germplasm conservation efforts. This study aimed to establish an optimal protocol for the storage and sowing of synthetic blackberry seeds obtained through the encapsulation of clump bases. The synthetic seeds were sown without storage (Control) and after storage periods of 30, 60, and 120 days at 4 °C and 25 °C in the dark, in three different substrates (agarised, perlite, and potting). After forty-five days from sowing viability, regeneration rate, shoot and root numbers and lengths, as well as fresh and dry weights of the plantlets, were assessed. Results indicated that agarised substrate consistently exhibited favourable outcomes, with sustained regeneration rates and robust plantlet development even after prolonged storage at 4 °C. Synthetic seeds sown in perlite and potting substrates demonstrated enhanced regeneration rates following storage at 4 °C for 60 and 120 days. On the contrary, storage at 25 °C resulted in a notable decline in regeneration rate, highlighting its inadequacy for blackberry synthetic seed conservation purposes. These findings underscore the importance of sowing substrate selection and storage temperature in optimizing the storage and sowing protocols for synthetic blackberry seeds.Key message: A temperature storage of 4 °C and an agarised sowing substrate guarantee high regeneration rates for blackberry synthetic seeds up to 120 days of storage. [ABSTRACT FROM AUTHOR]

The correction notice from the World Journal of Urology addresses the interchange of Figures 1 and 2 in an article on the role of neoadjuvant chemotherapy in patients with Upper Tract Urothelial Carcinoma. The corrected figures now accurately depict stage-specific Kaplan-Meier analyses comparing survival probabilities between different patient groups. The authors of the original article are listed, and Springer Nature maintains neutrality regarding jurisdictional claims and affiliations. [Extracted from the article]

Patients with heart failure with reduced ejection fraction (HFrEF) and diabetes mellitus (DM) have an increased risk of adverse events, including thromboembolism. In this analysis, we aimed to explore the association between DM and HFrEF using data from the "Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction" (WARCEF) trial. We analyzed factors associated with DM using multiple logistic regression models and evaluated the effect of DM on long-term prognosis, through adjusted Cox regressions. The primary outcome was the composite of all-cause death, ischemic stroke, or intracerebral hemorrhage; we explored individual components as the secondary outcomes and the interaction between treatment (warfarin or aspirin) and DM on the risk of the primary outcome, stratified by relevant characteristics. Of 2294 patients (mean age 60.8 (SD 11.3) years, 19.9% females) included in this analysis, 722 (31.5%) had DM. On logistic regression, cardiovascular comorbidities, symptoms and ethnicity were associated with DM at baseline, while age and body mass index showed a nonlinear association. Patients with DM had a higher risk of the primary composite outcome (Hazard Ratio [HR] and 95% Confidence Intervals [CI]: 1.48 [1.24–1.77]), as well as all-cause death (HR [95%CI]: 1.52 [1.25–1.84]). As in prior analyses, no statistically significant interaction was observed between DM and effect of Warfarin on the risk of the primary outcome, in any of the subgroups explored. In conclusion, we found that DM is common in HFrEF patients, and is associated with other cardiovascular comorbidities and risk factors, and with a worse prognosis. [ABSTRACT FROM AUTHOR]

Purpose: The study aims to demonstrate the effects of Vitamin D (VD) supplementation, prior to oocyte pick-up within IVF protocols, in women with diverse VD status at the enrollment. Methods: A total of 204 women eligible for intra-cytoplasmatic sperm injection (ICSI) cycles were included in the study and two homogeneous groups were selected from the database. Both group of patients with normal VD baseline level (> 40 ng/ml) and patients with low VD baseline level (< 20 ng/ml) were divided into control group and treatment group. The control group followed the standard procedure. The treatment group was supplemented with vitamin D3 as cholecalciferol in combination with Myo-Inositol, folic acid, and melatonin 3 months before standard procedure, once a day in the evening. Results: VD levels significantly increased in the study group of low baseline VD, both in serum and in the follicular fluid compared to controls. The treatment induced a significant improvement of the embryo quality in both group of patients considered. Conclusion: Supplementation of VD in patients undergoing ICSI procedures significantly improved the number of top-quality embryos compared with the control group, either starting from VD normal baseline values or starting from low values. Trial registration number: 07/2018. [ABSTRACT FROM AUTHOR]

Purpose: To define a peak force of insertion (PFOI) threshold for ureteral damage during ureteral access sheath (UAS) placement on an experimental ureteral orifice model. Methods: A specially designed water tank using 2 laparoscopic 5 mm ports and 2 different size (10 Fr and 8 Fr) sealing cap adaptors (SCA) as ureteral orifices was used to perform the test. A 10–12 Fr UAS was fixed to a load cell and the force of insertion (FOI) was continuously recorded with a digital force gauge.13 experts in the field of endourology who participated performed 3 UAS insertions. The FOI was recorded initially with 10 Fr followed by 8 Fr SCA. On the final insertion, the orifice was obstructed, leaving a 5 cm length to insert the UAS. The experts were asked to "Stop at the point they anticipate ureteral damage, and they would not proceed in real life". Results: Using 10 Fr SCA the PFOI was 2.12 ± 0.58 Newton (N) (range:1.48–3.48) while 8 Fr SCA showed a PFOI 5.76 ± 0.96 N (range:4.05–7.35). Six of the experts, said they would stop proceeding when they reached above 5.1 N. Three experts had PFOI < 5.1 N and the other 4 stated they would go with PFOIs of 5.88, 6.16, 6.69 and 7.35 N when using SCA of 8 Fr.The highest load they would stop proceeding had a PFOI of 6.09 ± 1.87 N (range: 2.53–10.74). Conclusion: The PFOI threshold for ureteral damage inserting UAS of the experts is variable. Although FOI is a subjective perception, experience suggests that ureteral injury may occur at an average of 6.05 N perceived by surgeons' tactile feedback. In-vivo measurement of UAS PFOI may confirm a threshold. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is primarily a disease diagnosed in young and middle-aged adults. Although MS is a rare condition in pediatric age, an increasing rate of patients is diagnosed under the age of 18. The disabling nature of the disease cannot be reduced only to physical symptoms. Several additional symptoms such as cognitive impairment, fatigue, and psychological symptoms are common features of pediatric MS. The reviewed literature suggests that, despite the lower physical disability, children and adolescents diagnosed with MS are vulnerable to cognitive impairment even in the early stage of the disease. The neuropsychological profile of pediatric MS may resemble that of adult MS, including an impairment in attention/information processing speed, learning, verbal, and visuospatial memory. However, cognitive difficulties in children and adolescents are more likely to involve also general intelligence and linguistic abilities, presumably due to patients' younger age and cognitive growth stage. Cognitive difficulties, beyond physical disability and relapses, may have a considerable impact on learning and school achievement. Depression and fatigue are other highly prevalent disturbances in pediatric MS and may contribute to patients' low functional outcomes. Overall, these manifestations may cause considerable functional impairment on daily activities and quality of life that may require individualized rehabilitative treatment and extensive psychosocial care. Additional neuropsychological research evaluating larger samples, using more homogenous methods, and exploring the role of MS treatment on cognitive and psychological development is required. [ABSTRACT FROM AUTHOR]

Objectives: While a single 12-month treatment cycle (TrC) with anti-CGRP mAbs is not disease-modifying for most patients, there is limited understanding of the effects of multiple TrCs on migraine course. We evaluated whether a second TrC might modify the migraine course by comparing the occurrence of migraine relapse after discontinuation of the second TrC to that following the cessation of the first TrC. Methods: In a real-life, multicenter, prospective study we considered all consecutive patients diagnosed with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and treated with any anti-CGRP mAbs for ≥ 2 consecutive 12-month TrCs who were responders at week 12. The primary endpoint was the change in monthly migraine days (MMD) for HFEM or monthly headache days (MHD) for CM at the first month of treatment discontinuation after the second TrC (D2) compared to the first TrC (D1). Secondary endpoints included variations in monthly analgesic medications (MAM), Numeric Rating Scale (NRS), and Headache Impact Test (HIT-6) scores, ≥ 50%, ≥ 75%, and 100% response rates, and relapse from episodic migraine to CM and from no-medication overuse (MO) to MO at D2 vs. D1. Results: One-hundred-seventy-eight patients completed two 12-month TrCs with anti-CGRP mAbs. At D2, patients experienced a significant reduction in MMD (– 0.6, p = 0.028), MHD (– 2.6, p < 0.001), monthly analgesic medications (– 2.0, p < 0.001), and HIT-6 score (– 2.2, p < 0.001) compared to D1, indicating improved effectiveness. The ≥ 50% response rate at weeks 45–48 during the first TrC was 95.5%, while at weeks 45–48 of the second TrC was 99.4%. Corresponding rates at D1 was 20.2% whereas at D2 was 51.6% (p < 0.0001). No statistical difference emerged in ≥ 75% and 100% responders. The relapse rate from episodic migraine to CM at D2 was lower than at D1 (12.3% vs 30.4%; p = 0.0002) Fewer patients experienced relapse from no-MO to MO at D2 compared to D1 (29.5% vs 68.7%; p = 0.00001). Discussion: A second TrC with anti-CGRP mAbs demonstrated clinical improvements compared to the first one, as indicated by a milder migraine relapse at D2 compared to D1. Multiple TrCs with anti-CGRP mAbs could progressively modify migraine evolution by reducing CGRP-dependent neuroinflammatory nociceptive inputs to the brain. [ABSTRACT FROM AUTHOR]

Objective: Nearly 60% of migraine patients treated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway experience a ≥ 50% reduction in monthly migraine days (MMD) at 12 weeks compared to baseline (responders). However, approximately half of the patients not responding to anti-CGRP mAbs ≤ 12 weeks do respond ≤ 24 weeks (late responders). We assessed frequency and characteristics of patients responding to anti-CGRP mAbs only > 24 weeks (ultra-late responders). Methods: In this multicenter (n = 16), prospective, observational, real-life study, we enrolled all consecutive adults affected by high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM), with ≥ 3 prior therapeutic failures, treated with any anti-CGRP mAbs for ≥ 48 weeks. We defined responders patients with a ≥ 50% response rate ≤ 12 weeks, late responders those with a ≥ 50% response rate ≤ 24 weeks, and ultra-late responders those achieving a ≥ 50% response only > 24 weeks. Results: A total of 572 migraine patients completed ≥ 48 weeks of anti-CGRP mAbs treatment. Responders accounted for 60.5% (346/572), late responders for 15% (86/572), and ultra-late responders for 15.7% (90/572). Among ultra-late responders, 7.3% (42/572) maintained the ≥ 50% response rate across all subsequent time intervals (weeks 28, 32, 36, 40, 44, and 48) and were considered persistent ultra-late responders, while 8.4% (48/572) missed the ≥ 50% response rate at ≥ 1 subsequent time interval and were classified as fluctuating ultra-late responders. Fifty patients (8.7%) did not respond at any time interval ≤ 48 weeks. Ultra-late responders differed from responders for higher BMI (p = 0.033), longer duration of medication overuse (p < 0.001), lower NRS (p = 0.017) and HIT-6 scores (p = 0.002), higher frequency of dopaminergic symptoms (p = 0.002), less common unilateral pain—either alone (p = 0.010) or in combination with UAS (p = 0.023), allodynia (p = 0.043), or UAS and allodynia (p = 0.012)—a higher number of comorbidities (p = 0.012), psychiatric comorbidities (p = 0.010) and a higher proportion of patients with ≥ 1 comorbidity (p = 0.020). Conclusion: Two-thirds of patients not responding to anti-CGRP mAbs ≤ 24 weeks do respond later, while non-responders ≤ 48 weeks are quite rare (8.7%). These findings suggest to rethink the duration of migraine prophylaxis and the definition of resistant and refractory migraine, currently based on the response after 2–3 months of treatment. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine (CM) negatively impacts the quality of life of 2 to 4% of pediatric patients. In adults, CM is frequently linked to medication overuse headache (MOH), but there is a much lower prevalence of MOH in children. A suboptimal response to acute therapies may lead to their reduced use, thus preventing MOH development in children and adolescents. The frequency of patients with CM who do not respond to acute therapies was examined in the present study. We investigated whether the prevalence of MOH was different between responders and non-responders. We also examined whether patients receiving prophylactic therapy had an improved response to acute therapy. Finally, we investigated if there was a difference in the frequency of psychiatric comorbidities between responders and non-responders. Methods: We retrospectively analysed clinical data of all chronic pediatric migraineurs under the age of 18 referred to the Headache Centre at Bambino Gesù Children Hospital in June 2021 and February 2023. ICHD3 criteria were used to diagnose CM and MOH. We collected demographic data, including the age at onset of migraine and the age of the CM course. At baseline and after 3 months of preventive treatment, we evaluated the response to acute medications. Neuropsychiatric comorbidities were referred by the children's parents during the first attendance evaluation. Results: Seventy patients with CM were assessed during the chosen period. Paracetamol was tried by 41 patients (58.5%), NSAIDs by 56 patients (80.0%), and triptans by 1 patient (1.4%). Fifty-one participants (73%) were non-responder to the abortive treatment. The presence of MOH was detected in 27.1% of the whole populations. Regarding our primary aim, MOH was diagnosed in 29% of non-responder patients and 22% of responders (p > 0.05). All patients received preventative treatment. After 3 months of preventive pharmacological therapy, 65.4% of patients who did not respond to acute medications achieved a response, while 34.6% of patients who were non-responder remain non-responder (p < 0.05). Prophylactic therapy was also effective in 69% of patients who responded to acute medication (p < 0.05). Psychiatric comorbidities were detected in 68.6% of patients, with no difference between responders and non-responders (72.2% vs. 67.3%; p = 0.05). Conclusions: Despite the high prevalence of unresponsiveness to acute therapies in pediatric CM, it does not act as a protective factor for MOH. Moreover, responsiveness to acute drugs is improved by pharmacological preventive treatment and it is not affected by concomitant psychiatric comorbidities. [ABSTRACT FROM AUTHOR]

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Molecular property prediction is a fundamental task in the field of drug discovery. Several works use graph neural networks to leverage molecular graph representations. Although they have been successfully applied in a variety of applications, their decision process is not transparent. In this work, we adapt concept whitening to graph neural networks. This approach is an explainability method used to build an inherently interpretable model, which allows identifying the concepts and consequently the structural parts of the molecules that are relevant for the output predictions. We test popular models on several benchmark datasets from MoleculeNet. Starting from previous work, we identify the most significant molecular properties to be used as concepts to perform classification. We show that the addition of concept whitening layers brings an improvement in both classification performance and interpretability. Finally, we provide several structural and conceptual explanations for the predictions. [ABSTRACT FROM AUTHOR]

Suspect screening and untargeted analysis using UHPLC-qToF are two advanced analytical approaches now used to achieve an extensive chemical profile of samples, which are then typically confirmed through targeted analysis. These techniques can detect a large number of chemical features simultaneously and are currently being introduced into the study of contaminants of emerging concern (CECs) and into the study of the extent of human chemical exposure (the exposome). Here is described the use of these techniques to characterize chemical mixtures derived from the OECD 301F ready biodegradability test (RBT) of a chemical and natural formulation currently used to treat reflux disease and functional dyspepsia. Untargeted analysis clearly evidenced a different behavior between formulations containing only natural products with respect to that containing synthetic and non-naturally occurring substances. Suspect screening analysis improved the untargeted analysis of the omeprazole-based medicine, leading to the tentative identification of a number of omeprazole-derived transformation products, thereby enabling their preliminary quali-quantitative evaluation. Targeted analysis was then performed to confirm the preliminary data gained from the suspect screening approach. The validation of the analytical method for the quantitative determination of omeprazole and its major metabolite, omeprazole sulphide, has provided robust data to evaluate the behavior of omeprazole during the OECD 301F test. Using advanced analytical approaches, the RBT performed on the two products under investigation confirmed that omeprazole is not readily biodegradable, while the medical device made of natural substances has proven to be readily biodegradable. [ABSTRACT FROM AUTHOR]

Background: The clinical management of malignant melanoma (MM) has undergone a significant revolution with the implementation of immune checkpoint inhibitors (ICIs). While these therapeutic agents stimulate the host immune system against cancer, they may also lead to immune-related adverse events (IrAEs). Positron emission computed tomography (PET/CT) with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) has proven successful in detecting IrAEs in cancer patients undergoing ICI. In our case, we report a rare occurrence of ICIs-induced concomitant thyroiditis and orchitis detected on [18F]FDG PET/CT. Case presentation: We present a case involving a 61-year-old man referred to our hospital due to MM. Following surgical excision and sentinel lymph node mapping, he underwent an initial [18F]FDG PET/CT, which yielded negative results. However, a follow-up PET/CT after 9 months revealed metastases in the lungs and lymph nodes. Subsequently, he initiated an ICI-based therapeutic regimen. After 3 months, he reported progressively worsening fatigue and the onset of testicular pain. A testicular ultrasound showed heterogeneous echotexture in both testicles with mildly increased vascularity. A subsequent PET/CT demonstrated complete regression of previously described pathological lesions in the lungs and metastatic lymph nodes. However, diffusely increased tracer uptake was observed in both the thyroid gland and testicles, findings absent in the pre-ICI examination. These were interpreted as IrAEs and promptly treated with corticosteroids, resulting in complete resolution of symptoms. Conclusions: [18F]FDG PET/CT plays a crucial role in staging and monitoring treatment response in cancer patients. When assessing subjects undergoing ICI-based therapies, particular emphasis should be given to detecting unusual IrAEs, as exemplified in our case. [ABSTRACT FROM AUTHOR]

The high metabolic flexibility and biodiversity of microalgae make them promising systems for the production of chemicals and high-value metabolites to be utilized in various industrial applications. Currently, microalgae are primarily cultivated in phototrophic processes or in fermenters using glucose as substrate. However, such configurations are often too costly for the majority of potential applications and require improvements. The use of acetate as substrate to enhance biomass productivity and reduce cost and environmental impacts is a promising solution. In a future bio-based economy, acetate can serve as an excellent intermediate to link many industrial facilities, as it can be synthesized using different technologies from renewable resources as CO2 and waste. This work provides a detailed description of acetate synthesis processes alternative to the conventional methanol carbonylation, including the pros and cons of each: aerobic and anaerobic fermentations; thermochemical treatments; C1 gas fermentation; microbial electrosynthesis and artificial photosynthesis. Additionally, the utilization of acetate as substrate for microalgae growth in mixotrophic and heterotrophic conditions is reviewed, covering key metabolic and engineering aspects (strains, yields, growth rate, inhibition, productivity, process configuration). These aspects serve as guidelines for a rationale design of an algal cultivation process based on acetate as a carbon source. Finally, the review critically assesses the state of the art of coupling of acetate-rich streams with algal biomass production, highlighting the pros and cons and addressing the main knowledge gaps to be filled through future research. [ABSTRACT FROM AUTHOR]

Geodetic time series are usually modeled with a deterministic approach that includes trend, annual, and semiannual periodic components having constant amplitude and phase-lag. Although simple, this approach neglects the time-variability or stochasticity of trend and seasonal components, and can potentially lead to inadequate interpretations, such as an overestimation of global navigation satellite system (GNSS) station velocity uncertainties, up to masking important geophysical phenomena. In this contribution, we generalize previous methods for determining trends and seasonal components and address the challenge of their time-variability by proposing a novel linear additive model, according to which (i) the trend is allowed to evolve over time, (ii) the seasonality is represented by a fractional sinusoidal waveform process (fSWp), accounting for possible non-stationary cyclical long-memory, and (iii) an additional serially correlated noise captures the short term variability. The model has a state space representation, opening the way for the evaluation of the likelihood and signal extraction with the support of the Kalman filter (KF) and the associated smoothing algorithm. Suitable enhancements of the basic methodology enable handling data gaps, outliers, and offsets. We demonstrate the advantage of our method with respect to the benchmark deterministic approach using both observed and simulated time series and provide a fair comparison with the Hector software. To that end, various geodetic time series are considered which illustrate the ability to capture the time-varying stochastic seasonal signals with the fSWp. [ABSTRACT FROM AUTHOR]

Available knowledge on the European white oaks (Quercus, sect. Quercus) plastome still exhibits large gaps, mostly in respect of detailed phylogeny and information from southern Europe and adjacent Near East. We investigated DNA sequence polymorphism at two plastid loci on 270 individuals representing 13 white oak species/taxa and retrieved several hundred sequences of the same two DNA regions from GenBank to fill the above gaps, and contribute to a better understanding of white oak diversity and evolution. The modern European sect. Quercus species exhibits a poorly differentiated plastid DNA, despite its current highly diversified taxonomy. Twenty-nine haplotypes were identified across the Euro-Mediterranean and Near East regions, including two ancestral variants that are westerly and south-easterly partitioned. Other high- and low-frequency haplotypes also showed a well-structured geographic distribution consistent with the current phytogeographic framework of the European continent. The climatic and geological events that characterized the end of the Tertiary and Quaternary periods played a crucial role in triggering haplotype mixing, isolation, and in offering niche opportunities for more recent diversification. Euro-Mediterranean southern territories host a high and as yet poorly studied genetic variation; the role of the Italian Peninsula as a crossroad and threshold for haplotype diversity and distribution clearly emerges from this study. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) is recommended in patients with upper tract urothelial carcinoma (UTUC) only when computed tomography (CT) is contraindicated. However, CT does not allow distinguishing ureter wall layers, making impossible to assess muscle invasion, a factor contributing to differentiate high- from low-risk UTUCs, which require different therapeutic approaches. We investigated the feasibility of MRI assessment of UTUC muscle invasion. Methods: From June 2022 to March 2023, we prospectively enrolled patients suspected of UTUC, i.e., with positive urinary tract ultrasound and/or ureteroscopy, or positive urinary cytology and/or hematuria but negative cystoscopy and bladder ultrasound at two Italian centers. They underwent CT followed by MRI (≤ 24 h apart), independently reported by two experienced radiologists, blinded from histopathology results. After imaging confirmation, they all underwent nephroureterectomy and histopathology analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the receiver operating characteristic curve (AUC) were calculated. Results: Thirty-nine lesions were detected in 30 patients on both CT and MRI. Muscle-invasive UTUC prevalence was 81% (21/26) among patients with MRI suspicion and 8% (1/13) among those without MRI suspicion (p < 0.001). Considering the assessment of muscle-layer invasion, the more experienced reader achieved 95% sensitivity (95% confidence interval 82−100), 71% specificity (47−88), 81% PPV (63−93), 92% NPV (70−100), 85% accuracy (67−96), and 0.84 AUC (0.70−0.98). Inter-reader agreement was substantial (κ = 0.73). Conclusions: MRI showed a promising diagnostic performance for the assessment of UTUC risk of muscle invasion. Relevance statement: Resulting feasible both in technical and clinical terms, MRI could be helpful for upper tract urothelial carcinomas pre-operative risk stratification, to allow a personalized patients' management. These results play in favor of promoting preoperative MRI for UTUC, as already proven for bladder cancer. Key points: • Muscle invasion is a crucial information for tailored treatments of upper tract urothelial carcinomas. • CT does not distinguish ureter wall layers, making muscle invasion risk assessment not feasible. • MRI was shown to reliably diagnose muscle-layer invasion by upper tract urothelial carcinomas (sensitivity 95%, specificity 71%). [ABSTRACT FROM AUTHOR]

Background: Despite hypothalamus has long being considered to be involved in the pathophysiology of cluster headache, the inconsistencies of previous neuroimaging studies and a limited understanding of the hypothalamic areas involved, impede a comprehensive interpretation of its involvement in this condition. Methods: We used an automated algorithm to extract hypothalamic subunit volumes from 105 cluster headache patients (57 chronic and 48 episodic) and 59 healthy individuals; after correcting the measures for the respective intracranial volumes, we performed the relevant comparisons employing logist regression models. Only for subunits that emerged as abnormal, we calculated their correlation with the years of illness and the number of headache attacks per day, and the effects of lithium treatment. As a post-hoc approach, using the 7 T resting-state fMRI dataset from the Human Connectome Project, we investigated whether the observed abnormal subunit, comprising the paraventricular nucleus and preoptic area, shows robust functional connectivity with the mesocorticolimbic system, which is known to be modulated by oxytocin neurons in the paraventricular nucleus and that is is abnormal in chronic cluster headache patients. Results: Patients with chronic (but not episodic) cluster headache, compared to control participants, present an increased volume of the anterior–superior hypothalamic subunit ipsilateral to the pain, which, remarkably, also correlates significantly with the number of daily attacks. The post-hoc approach showed that this hypothalamic area presents robust functional connectivity with the mesocorticolimbic system under physiological conditions. No evidence of the effects of lithium treatment on this abnormal subunit was found. Conclusions: We identified the ipsilateral-to-the-pain antero-superior subunit, where the paraventricular nucleus and preoptic area are located, as the key hypothalamic region of the pathophysiology of chronic cluster headache. The significant correlation between the volume of this area and the number of daily attacks crucially reinforces this interpretation. The well-known roles of the paraventricular nucleus in coordinating autonomic and neuroendocrine flow in stress adaptation and modulation of trigeminovascular mechanisms offer important insights into the understanding of the pathophysiology of cluster headache. [ABSTRACT FROM AUTHOR]

The 2MACE score was specifically developed as a risk-stratification tool in atrial fibrillation (AF) to predict cardiovascular outcomes. We evaluated the predictive ability of the 2MACE score in the GLORIA-AF registry. All eligible patients from phase II/III of the prospective global GLORIA-AF registry were included. Major adverse cardiac events (MACEs) were defined as the composite outcome of stroke, myocardial infarction and cardiovascular death. Cox proportional hazards were used to examine the relationship between the 2MACE score and study outcomes. Predictive capability of the 2MACE score was investigated using receiver-operating characteristic curves. A total of 25,696 patients were included (mean age 71 years, female 44.9%). Over 3 years, 1583 MACEs were recorded. Patients who had MACE were older, with more cardiovascular risk factors and were less likely to be managed using a rhythm-control strategy. The median 2MACE score in the MACE and non-MACE groups were 2 (IQR 1–3) and 1 (IQR 0–2), respectively (p < 0.001). The 2MACE score was positively associated with an increase in the risk of MACE, with a score of ≥ 2 providing the best combination of sensitivity (69.6%) and specificity (51.6%), HR 2.47 (95% CI, 2.21–2.77). The 2MACE score had modest predictive performance for MACE in patients with AF (AUC 0.655 (95% CI, 0.641–0.669)). Our analysis in this prospective global registry demonstrates that the 2MACE score can adequately predict the risk of MACE (defined as myocardial infarction, CV death and stroke) in patients with AF. Clinical trial registration:http://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007 and NCT01937377 [ABSTRACT FROM AUTHOR]

Purpose: To identify laser lithotripsy settings used by experts for specific clinical scenarios and to identify preventive measures to reduce complications. Methods: After literature research to identify relevant questions, a survey was conducted and sent to laser experts. Participants were asked for preferred laser settings during specific clinical lithotripsy scenarios. Different settings were compared for the reported laser types, and common settings and preventive measures were identified. Results: Twenty-six laser experts fully returned the survey. Holmium-yttrium-aluminum-garnet (Ho:YAG) was the primary laser used (88%), followed by thulium fiber laser (TFL) (42%) and pulsed thulium-yttrium-aluminum-garnet (Tm:YAG) (23%). For most scenarios, we could not identify relevant differences among laser settings. However, the laser power was significantly different for middle-ureteral (p = 0.027), pelvic (p = 0.047), and lower pole stone (p = 0.018) lithotripsy. Fragmentation or a combined fragmentation with dusting was more common for Ho:YAG and pulsed Tm:YAG lasers, whereas dusting or a combination of dusting and fragmentation was more common for TFL lasers. Experts prefer long pulse modes for Ho:YAG lasers to short pulse modes for TFL lasers. Thermal injury due to temperature development during lithotripsy is seriously considered by experts, with preventive measures applied routinely. Conclusions: Laser settings do not vary significantly between commonly used lasers for lithotripsy. Lithotripsy techniques and settings mainly depend on the generated laser pulse’s and generator settings’ physical characteristics. Preventive measures such as maximum power limits, intermittent laser activation, and ureteral access sheaths are commonly used by experts to decrease thermal injury-caused complications. [ABSTRACT FROM AUTHOR]

This study sought to analyze the ablation rates of Holmium:YAG (Ho:YAG) and thulium fiber laser (TFL) under different settings combinations. Lasering was carried out by a computed spiral pattern through a stepper motor bearing a laser fiber. BegoStones were placed inside a water container and lasered therein and the ablation rate was calculated. Different combinations were tested for ~12 Watts (W) for Ho:YAG and TFL lasers. Further 25 W combination for TFL were conducted testing higher frequencies. One-hundred-one experiments were conducted. Under ~12 W, the highest ablation rate for Ho:YAG was obtained with 40 Hz/0.3 J, and Virtual Basket™ (VB) emission mode [114.35 (88.30 – 126.40) mg/min] whereas for TFL, using 40 Hz/0.3 J, and long pulse [143.40 (137.40 – 146) mg/min]. A matched-comparison for 12 Hz/1 J settings showed that TFL outperformed Ho:YAG using medium pulse [63.30 (55.30 – 81.30) vs 132.00 (115.70 – 228.60) mg/min, p=0.016] and long pulse [62.90 (51.60 – 78.90) vs 134.70 (110.60 – 149.30) mg/min, p=0.016]. In the 40 Hz/0.3 J settings, TFL outperformed Ho:YAG (p=0.034). Nonetheless, Ho:YAG with VB’s ablation rate increased [114.35 (88.30 – 126.40)], being comparable to that of TFL with medium pulse [127.5 (88.90 – 141.70)] (p=0.400). In TFL 25 W experiments, the ablation rate of 500 Hz / 0.05 J, was higher than those of 1000 Hz / 0.025 J (p=0.049). TFL ablation rate is higher than that of Ho:YAG. Moreover, the Virtual Basket™ emission mode, increased Ho:YAG ablation rates, resulting reaching similar to that of TFL in certain modalities. [ABSTRACT FROM AUTHOR]

The benefits of green areas mostly depend on the trees' dimension, which in the urban environment is not as predictable as it is in woodland. Growth models based on tree height and tree diameter at breast height have been largely employed to predict tree growth also in urbanised contexts. However, city environments differ from natural ones, and in addition to geographical influence, they present high variability in growth conditions within a few metres. Different urban conditions may influence tree vertical and diametral growth. The present study aims to jointly consider the effect of urban environment, maintenance practices and available space on the size growth of some tree species. Dendrometrical, space, management and status parameters of the sampled trees were collected during field surveys 14 years apart. Tree height and diameter at breast height data interpolations were realised and charted by an open-source graphing calculator to build three different growth equations (linear, logarithmic and logistic) for each of the five species considered regardless of tree growth conditions. The comparison between the comprehensive best-fitting models realised within this study and a USA inventory-based study highlighted quite similar tree growth trends, probably due to the consideration of both constrained and unconstrained trees. Furthermore, a study on the curves of same-growth condition trees of the same species was conducted. Generally, heavy pruning techniques such as control and pollard pruning, characterised by the removal of a consistent part of the tree crown, stand out as the main growth-limiting factor for the different species. [ABSTRACT FROM AUTHOR]

Purpose: To summarise the current knowledge regarding diagnostics, prognostication and follow-up in upper tract urothelial carcinoma (UTUC). Methods: A scoping review combined with expert opinion was applied to provide an overview of the current research field. Based on the published literature and the experts' own experience and opinions, consensus was reached through presentations and discussions at the meeting Consultation on UTUC II in Stockholm 2022. Results: The strongest prognostic factors in UTUC are tumour grade and stage. They are correlated, and grade is used for indirect staging. The diagnostic examinations should include multiphase computed tomography urography (CTU) with corticomedullary phase, and urethrocystoscopy with cytology. If there is no clear diagnosis for clinical decision-making, ureterorenoscopy (URS) with focal cytology and biopsies should be performed. Both WHO classification systems (1973/1999 and 2004/2016) should be used. Novel biomarker tests are not yet widespread nor recommended for the detection of UTUC. Long-term, regular follow-up, including URS in patients who have had organ-sparing treatment, is important to check for tumour recurrences, intravesical recurrences, metastases and progression of the tumour. Conclusion: Proper diagnostics with correct grading of UTUC are necessary for appropriate treatment decisions. The diagnostics should include CTU with corticomedullary phase, urine or bladder cytology, URS with focal barbotage cytology, and biopsies when needed for proper diagnosis and risk stratification. Regular, long-term follow-ups are fundamental, due to the high rate of recurrence and risk of progression. [ABSTRACT FROM AUTHOR]

Quantum conference key agreement (QCKA) allows multiple users to establish a secure key from a shared multi-partite entangled state. In a quantum network, this protocol can be efficiently implemented using a single copy of a N-qubit Greenberger-Horne-Zeilinger (GHZ) state to distil a secure N-user conference key bit, whereas up to N-1 entanglement pairs are consumed in the traditional pair-wise protocol. We demonstrate the advantage provided by GHZ states in a testbed consisting of a photonic six-user quantum network, where four users can distil either a GHZ state or the required number of Bell pairs for QCKA using network routing techniques. In the asymptotic limit, we report a more than two-fold enhancement of the conference key rate when comparing the two protocols. We extrapolate our data set to show that the resource advantage for the GHZ protocol persists when taking into account finite-key effects. [ABSTRACT FROM AUTHOR]

The development of probabilistic maps associated with lava flow inundation is essential to assess hazard in open vent volcanoes, especially those that have highly urbanized flanks. In this study we present the new lava flow hazard map linked to the summit eruptions of Mt. Etna, which has been developed using a probabilistic approach that integrates statistical analyses of the volcanological historical data with numerical simulations of lava flows. The statistical analysis of volcanological data (including vent location, duration and lava volumes) about all summit eruptions occurred since 1998 has allowed us both to estimate the spatiotemporal probability of future vent opening and to extract the effusion rate curves for lava flow modelling. Numerical simulations were run using the GPUFLOW model on a 2022 Digital Surface Model derived from optical satellite images. The probabilistic approach has been validated through a back-analysis by calculating the fit between the expected probabilities of inundation and the lava flows actually emplaced during the 2020-2022 period. The obtained map shows a very high probability of inundation of lava flows emitted at vents linked to the South East Crater, according to the observation of the eruptive dynamics in the last decades. [ABSTRACT FROM AUTHOR]

Purpose: To highlight and compare experts' laser settings during endoscopic laser treatment of upper tract urothelial carcinoma (UTUC), to identify measures to reduce complications, and to propose guidance for endourologists. Methods: Following a focused literature search to identify relevant questions, a survey was sent to laser experts. We asked participants for typical settings during specific scenarios (ureteroscopy (URS), retrograde intrarenal surgery (RIRS), and percutaneous treatment). These settings were compared among the reported laser types to find common settings and limits. Additionally, we identified preventive measures commonly applied during surgery. Results: Twenty experts completed the survey, needing a mean time of 12.7 min. Overall, most common laser type was Holmium–Yttrium–Aluminum–Garnet (Ho:YAG) (70%, 14/20) followed by Thulium fiber laser (TFL) (45%, 9/20), pulsed Thulium–Yttrium–Aluminum–Garnet (Tm:YAG) (3/20, 15%), and continuous wave (cw)Tm:YAG (1/20, 5%). Pulse energy for the treatment of distal ureteral tumors was significantly different with median settings of 0.9 J, 1 J and 0.45 J for Ho:YAG, TFL and pulsed Tm:YAG, respectively (p = 0.048). During URS and RIRS, pulse shapes were significantly different, with Ho:YAG being used in long pulse and TFL in short pulse mode (all p < 0.05). We did not find further disparities. Conclusion: Ho:YAG is used by most experts, while TFL is the most promising alternative. Laser settings largely do not vary significantly. However, further research with novel lasers is necessary to define the optimal approach. With the recent introduction of small caliber and more flexible scopes, minimal-invasive UTUC treatment is further undergoing an extension of applicability in appropriately selected patients. [ABSTRACT FROM AUTHOR]

We aimed to investigate the sex-related differences in the clinical course of patients with Atrial Fibrillation (AF) enrolled in the Asia–Pacific-Heart-Rhythm-Society Registry. Logistic regression was utilized to investigate the relationship between sex and oral anticoagulant, rhythm control strategies and the 1-year chance to maintain sinus rhythm. Cox-regression was utilized to assess the 1-year risk of all-cause, and cardiovascular death, thromboembolic events, acute coronary syndrome, heart failure, and major bleeding. In the whole cohort (4121 patients, 69 ± 12 years,34.3% female), females had different cardiovascular risk factors, clinical manifestations, and disease perceptions than men, with more advanced age (72 ± 11 vs 67 ± 12 years, p < 0.001) and dyslipidemia (36.7% vs 41.7%, p = 0.002). Coronary artery disease was more prevalent in males (21.1% vs 16.1%, p < 0.001) as well as the use of antiplatelet drugs. Females had a higher use of oral anticoagulant (84.9% vs 81.3%, p = 0.004) but this difference was non-significant after adjustment for confounders. On multivariable analyses, females were less often treated with rhythm control strategies (Odds Ratio [OR] 0.44,95% Confidence Interval [CI] 0.38–0.51) and were less likely to maintain sinus rhythm (OR 0.27, 95% CI 0.22–0.34) compared to males. Cox-regressions analysis showed no sex-related differences for the risk of death, cardiovascular, and bleeding. The clinical management of Asian AF patients should consider several sex-related differences. [ABSTRACT FROM AUTHOR]

At active volcanoes recurring eruptive events, erosive processes and collapses modify the edifice morphology and impact monitoring and hazard mitigation. At Etna volcano (Italy) between February and October 2021, 57 paroxysmal events occurred from the South-East Crater (SEC), which is currently its most active summit crater. Strombolian activity and high lava fountains (up to 4 km) fed lava flows towards the east, south and south-west, and caused fallout of ballistics (greater than 1 m in diameter) within 1–2 km from the SEC. The impacted area does not include permanent infrastructure, but it is visited by thousands of tourists. Hence, we rapidly mapped each lava flow before deposits became covered by the next event, for hazard mitigation. The high frequency of the SEC paroxysms necessitated integration of data from three remote sensing platforms with different spatial resolutions. Satellite (Sentinel-2 MultiSpectral Instrument, PlanetScope, Skysat and Landsat-8 Operational Land Imager) and drone images (visible and thermal) were processed and integrated to extract digital surface models and orthomosaics. Thermal images acquired by a permanent network of cameras of the Istituto Nazionale di Geofisica e Vulcanologia were orthorectified using the latest available digital surface model. This multi-sensor analysis allowed compilation of a geodatabase reporting the main geometrical parameters for each lava flow. A posteriori analysis allowed quantification of bulk volumes for the lava flows and the SEC changes and of the dense rock equivalent volume of erupted magma. The analysis of drone-derived digital surface models enabled assessment of the ballistics' distribution. The developed methodology enabled rapidly and accurate characterisation of frequently occurring effusive events for near real-time risk assessment and hazard communication. [ABSTRACT FROM AUTHOR]

Plants have always been able to adapt to climate change by reacting through various responses, mainly at the phenological level. The aim of this work is to investigate the behavior of specific tree species located in two phenological gardens in central Italy in relation to the temperature increases recorded in recent years. Specifically, four main phenological phases, BBCH_11, BBCH_19, BBCH_91, and BBCH_65, were monitored during a 14-year time period. The data of the weeks corresponding to the first appearance of each phenological phase and the respective heat accumulations for each species were cross-referenced with the meteorological data recorded by the stations in the two considered areas. Based on average temperature, calculated over reference periods, the species were divided by creating "warm" year groups and "cold" year groups so as to better highlight any differences in the behavior of the same species. In addition, a strong correlation was shown between the maximum temperatures in February and the advances of phenological phases BBCH_11 and BBCH_65. Most of the tree species have shown strong adaptation to climate warming, changing the period of occurrence of the phases themselves. [ABSTRACT FROM AUTHOR]

Infrasound signals are used to investigate and monitor active volcanoes during eruptive and degassing activity. Infrasound amplitude information has been used to estimate eruptive parameters such as plume height, magma discharge rate, and lava fountain height. Active volcanoes are characterized by pronounced topography and, during eruptive activity, the topography can change rapidly, affecting the observed infrasound amplitudes. While the interaction of infrasonic signals with topography has been widely investigated over the past decade, there has been limited work on the impact of changing topography on the infrasonic amplitudes. In this work, the infrasonic signals accompanying 57 lava fountain paroxysms at Mt. Etna (Italy) during 2021 were analyzed. In particular, the temporal and spatial variations of the infrasound amplitudes were investigated. During 2021, significant changes in the topography around the most active crater (the South East Crater) took place and were reconstructed in detail using high resolution imagery from unoccupied aerial system surveys. Through analysis of the observed infrasound signals and numerical simulations of the acoustic wavefield, we demonstrate that the observed spatial and temporal variation in the infrasound signal amplitudes can largely be explained by the combined effects of changes in the location of the acoustic source and changes in the near-vent topography, together with source acoustic amplitude variations. This work demonstrates the importance of accurate source locations and high-resolution topographic information, particularly in the near-vent region where the topography is most likely to change rapidly and illustrates that changing topography should be considered when interpreting local infrasound observations over long time scales. [ABSTRACT FROM AUTHOR]

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982. [ABSTRACT FROM AUTHOR]

Purpose: To report long-term oncologic and functional outcomes of a large consecutive single center series of Robot-assisted radical cystectomy (RARC)- intracorporeal (IC) Urinary Diversion (UD), identifying their predicting factors. Methods: A single center Bladder cancer (BC) database was queried for "RARC" and "ICUD", including patients treated between January 2012 and September 2020. Kaplan–Meier curves were assessed disease-free (DFS), cancer-specific (CSS) and overall survival (OS) probability. Univariable (UV) and multivariable (MV) analysis were adopted to identify predictors of DFS, CSS and OS. Kaplan–Meier method evaluated day- and night-time continence recovery probabilities; UV and MV analysis were adopted to identify predictors of Day-time continence. Results: Overall, 251 patients were included. Among them, 192 patients underwent intracorporeal ileal orthotopic neobladder (ION) (76.5%). Five-year DFS, CSS and OS rates were 66.5%, 65.4% and 61.5%; pT stage ≥ 3 and pathologic nodal involvement were identified as negative independent predictors of DFS (HR 2.39, p = 0.001, HR 4.64, p ≤ 0.001), CSS (HR 2.20, p = 0.01, HR 3.97, p < 0.001) and OS (HR 2.25, p = 0.005, HR 3.95, p < 0.001). In RARC-ION patients, Trifecta rate was 64.1%. One-year day- and night-time continence rates were 78.6% and 48.3%. Age (HR 0.98, p = 0.03), female gender (HR 0.57, p = 0.008) and complications Clavien grade ≥ 3 (HR 0.55, p = 0.03) were identified as independent predictors of day-time incontinence. Conclusions: Long-term oncologic outcomes and their predicting factors seem aligned to the largest historical open series and multi-institutional robotic series data. According to the identified predicting factors undermining a proper achievement of day-time continence, this represents an objective support, in order to properly advice specific sub-group of patients. [ABSTRACT FROM AUTHOR]