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Yvan Vandenplas,1 Helen A Brough,2– 4 Alessandro Fiocchi,5 Mohamad Miqdady,6 Zakiudin Munasir,7 Silvia Salvatore,8 Nikhil Thapar,9 Carina Venter,10 Mario C Vieira,11 Rosan Meier12,13 1Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium; 2Department Women and Children’s Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK; 3Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, London, UK; 4Children’s Allergy Service, Evelina Children’s Hospital, Guy’s and St. Thomas’s NHS Foundation Trust, London, UK; 5Translational Research in Pediatric Specialities Area, Division of Allergy, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio, Rome, Italy; 6Department of Pediatrics, Sheikh Khalifa Medical City, College of Medicine & Health Sciences, Khalifa University, Khalifa, United Arab Emirates; 7Department of Child Health, Ciptomangunkusumo Hospital-Medical Faculty Universitas Indonesia, Jakarta, Indonesia; 8Pediatric Department, Hospital “F. Del Ponte”, University of Insubria, Varese, Italy; 9Gastroenterology, Hepatology and Liver Transplant, Queensland Children’s Hospital, Brisbane, Queensland, Australia; 10University of Colorado, Children’s Hospital Colorado, Denver, CO, USA; 11Center for Pediatric Gastroenterology -Hospital Pequeno Príncipe, Curitiba, Brazil; 12Department of Paediatrics, Imperial College, London, UK; 13Department Nutrition and Dietetics, University of Winchester, Winchester, UKCorrespondence: Yvan VandenplasVrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, BelgiumEmail Yvan.vandenplas@uzbrussel.beAbstract: Exclusive breast feeding is recommended in all guidelines as the first choice feeding. Cow milk allergy (CMA) can be diagnosed by a diagnostic elimination diet for 2 to 4 weeks with a hypo-allergenic formula, followed by a challenge test with intact cow milk protein. The most often used hypo-allergenic formula for the diagnostic elimination diet and the therapeutic diet is a CM based extensive hydrolysate. CM-based partial hydrolysates cannot be recommended in the management of CMA because of insufficient efficacy and possible reactions, but about half of the infants with CMA may tolerate a partial hydrolysate. The pros and cons of other dietary options are discussed in this paper. The use of an amino acid-based formula and/or rice based hydrolysate formula during the diagnostic elimination and therapeutic diet is debated. When available, there is sufficient evidence to consider rice hydrolysates as an adequate alternative to CM-based hydrolysates, since some infants will still react to the CM hydrolysate. The pros and cons of dietary options such as soy formula, buckwheat, almond, pea or other plant based dietary products are discussed. Although the majority of the plant-based beverages are nutritionally inadequate, some are nutritionally adapted for toddlers. However, accessibility and content vary by country and, thus far there is insufficient evidence on the efficacy and tolerance of these plant-based drinks (except for soy formula and rice hydrolysates) to provide an opinion on them.Conclusion: A diagnostic elimination diet, followed by a challenge remains the diagnostic standard. The use of an awareness tool may result in a decrease of delayed diagnosis. Breastmilk remains the ideal source of nutrition and when not available a CM extensively hydrolyzed formula, rice hydrolysate or amino acid formula should be recommended. More evidence is needed regarding plant-based drinks.Keywords: amino acid formula, challenge test, cow milk allergy, hydrolysate, plant-based drink, rice hydrolysate, soy formula

Stefano Salvatore,1 Montserrat Espuña-Pons,2 Andrea Tubaro3 1Urogynecology Unit, Obstetrics and Gynecology Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, Italy; 2Urogynecology Unit, ICGON, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain; 3Department of Urology, Sant’Andrea Hospital, Sapienza University, Rome, ItalyCorrespondence: Stefano SalvatoreUrogynecology Unit, Obstetrics and Gynecology Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, ItalyTel +39 02 26432579Email stefanosalvatore@hotmail.comAbstract: Urgency, defined as “a sudden, compelling desire to pass urine which is difficult to defer”, is not always reported by patients with overactive bladder, and is not usually described in these words. Urgency is known to have a strong negative impact on patients’ quality of life and requires attention from healthcare professionals, as they play a key role in establishing the diagnosis and in deciding, together with the patient, the most appropriate treatment. This topic was debated during the symposium “Urinary Urgency: A Symptom in Need of a Cure?”, held at the 11th Annual Meeting of the European Urogynaecology Association (EUGA) in October 2018 in Milan, Italy. The presentation of two clinical cases, those of a young, active woman and a retired teacher, illustrated the importance of this cornerstone symptom and demonstrated how fesoterodine may represent an important option in the management of this condition. The experts concluded that the physician should not leave urgency undeclared or untreated; that the patient should be involved in the choice of treatment; and that fesoterodine, which offers flexible dosing and has proven, consistent positive results on urgency episodes and urgency urinary incontinence, with very low/no risk of impairment of cognitive function, appears to be one of the good choices in the treatment of this symptom.Keywords: antimuscarinic agents, cognitive function, fesoterodine, incontinence, overactive bladder

The thirty-nine extant genera of Conoderinae known to occur in North America, Central America, and the Caribbean are reviewed based on external morphology. An identification key is provided along with diagnoses, distributions, species counts, and natural history information, when known, for each genus. Morphological character systems of importance for weevil classification are surveyed, potential relationships among the tribes and genera are discussed, and groups most in need of taxonomic and phylogenetic attention are identified. The following genera are transferred to new tribes: Acoptus LeConte, 1876 from the Lechriopini to the Othippiini (new placement) and the South American genus Hedycera Pascoe, 1870 from the Lechriopini to the Piazurini (new placement). Philides Champion, 1906 and Philinna Champion, 1906 are transferred from the Lechriopini to Conoderinae incertae sedis (new placement) although their placement as conoderines is uncertain. The species Copturomimus cinereus Heller, 1895 is designated as the type species of the genus Copturomimus Heller, 1895.

Qubit measurements are central to quantum information processing. In the field of superconducting qubits, standard readout techniques are limited not only by the signal-to-noise ratio, but also by state relaxation during the measurement. In this work, we demonstrate that the limitation due to relaxation can be suppressed by using the many-level Hilbert space of superconducting circuits: In a multilevel encoding, the measurement is corrupted only when multiple errors occur. Employing this technique, we show that we can directly resolve transmon gate errors at the level of one part in 10^{3}. Extending this idea, we apply the same principles to the measurement of a logical qubit encoded in a bosonic mode and detected with a transmon ancilla, implementing a proposal by Hann et al. [Phys. Rev. A 98, 022305 (2018)PLRAAN2469-992610.1103/PhysRevA.98.022305]. Qubit state assignments are made based on a sequence of repeated readouts, further reducing the overall infidelity. This approach is quite general, and several encodings are studied; the codewords are more distinguishable when the distance between them is increased with respect to photon loss. The trade-off between multiple readouts and state relaxation is explored and shown to be consistent with the photon-loss model. We report a logical assignment infidelity of 5.8×10^{-5} for a Fock-based encoding and 4.2×10^{-3} for a quantum error correction code (the S=2, N=1 binomial code). Our results not only improve the fidelity of quantum information applications, but also enable more precise characterization of process or gate errors.

The progression of non-alcoholic fatty liver disease (NAFLD) and the development of hepatic fibrosis is caused by changes in redox balance, leading to an increase of reactive oxygen species (ROS) levels. NAFLD patients are at risk of progressing to non-alcoholic steatohepatitis (NASH), associated to cardiovascular diseases (CVD), coronary heart disease and stroke. Heme Oxygenase-1 (HO-1) is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. The present work was directed to determine whether use of an inhibitor of HO-1 activity affects lipid metabolism and fibrosis process in hepatic cells. Oil Red assay and mRNA analysis were used to evaluate the triglycerides content and the lipid metabolism pathway in HepG2 cells. ROS measurement, RT-PCR and Soluble collagen assay were used to assess the intracellular oxidant, the fibrosis pathway and the soluble collagen in LX2 cells. The activity of HO-1 was inhibited using Tin Mesoporphyrin IX (SnMP). Our study demonstrates that a non-functional HO system results in an increased lipid storage and collagen release in hepatocytes. Consequently, an increase of HO-1 levels may provide a therapeutic approach to address the metabolic alterations associated with NAFLD and its progression to NASH.

Serena Salvatore, Aloisa Librando, Mariacristina Esposito, Enzo M VingoloDepartment of Ophthalmology, University La Sapienza, Polo Pontino, Alfredo Fiorini Hospital, Terracina, ItalyPurpose: To evaluate the usefulness of acoustic biofeedback by means of Mozart’s Sonata for Two Pianos in D Major K. 448 to maintain and/or restore visual performance in a patient with macular pucker and glaucoma.Methods: A 74-year-old patient with open angle glaucoma in both eyes and macular pucker in the right eye (RE) underwent visual rehabilitation with acoustic biofeedback by means of the MAIA™ Vision Training Module (Centervue, Padova, Italy) 10 minutes each eye once a week for 5 weeks. The patient was asked to move his eyes according to a sound which changed into Mozart’s Sonata for Two Pianos when the patient locked the fixation target.Results: Best-corrected visual acuity improved in his right eye (RE) and was stable in the left eye (LE). Fixation stability improved in both eyes, and retinal sensitivity decreased in the RE and improved in the LE. The characteristic of the macular pucker did not change during the training as demonstrated with optical coherence tomography. The patient was very satisfied with the training, as demonstrated by a 25-item questionnaire (National Eye Institute – Visual Functioning Questionnaire, NEI-VFQ-25). The patient’s reading speed and the character size which he was able to read improved in his RE.Conclusion: Music could enhance synaptic plasticity and affect neural learning and fixation training by means of MAIA vision training. Therefore it can improve visual performance in patients with macular pucker, postpone the surgical time, and assure a better quality of life for the patient.Keywords: glaucoma, macular cellophane, music, vision training

Enzo Maria Vingolo1,2, Mariacristina Esposito3, Aloisa Librando3, Yu-Hui Huang4, Serena Salvatore1,21Department of Ophthalmology, University La Sapienza of Rome, Terracina, Italy; 2UOC Santa Maria Goretti Hospital, Latina, Italy; 3Department of Ophthalmology, University La Sapienza of Rome, Rome, Italy; 4University of Illinois at Chicago, Chicago, IL, USABackground: The purpose of the study was to evaluate vitreoretinal interface (VRI) alteration with a short-wavelength scanning laser ophthalmoscope (swSLO), the Nidek F-10, and compare the results with those obtained by means of spectral-domain optical coherence tomography (SD-OCT).Methods: Thirty-six eyes were studied (20 patients, mean age 68 ± 12.3 years). All patients underwent a complete ophthalmologic examination, which comprised SD-OCT and Nidek F-10 analysis with short-wavelength blue laser. Eyes were divided into four groups depending on the degree of VRI alteration observed with the swSLO and SD-OCT. Statistical analysis was performed using the Chi-square test. P values less than 0.05 were considered statistically significant.Results: OCT analysis: eight eyes (22%) grade 0 (no abnormalities), 15 eyes (42%) grade 1 (preretinal cellophane); seven (19%) grade 2 (preretinal wrinkling); six (17%) grade 3 (macular pucker or hole). Nidek F-10 analysis: seven (19%) grade 0, 16 (45%) grade 1; seven (19%) grade 2; six (17%) grade 3. Chi-square = 0.099, P = 0.992. There was no statistically significant difference between the two instruments.Conclusion: Nidek F-10 allows both a quantitative and a qualitative evaluation of VRI and is equal to SD-OCT in detecting alteration of the inner portion of the retina, providing an easy way to evaluate and map differences in the inner vitreoretinal surface.Keywords: vitreoretinal interface, macular pucker, macular cellophane, optical coherence tomography (OCT), short wavelength scanning laser ophthalmoscope (swSLO), Nidek F-10

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.

Several studies highlight the role of inflammatory markers in thrombosis as well as in cancer. However, their combined role in cancer-associated deep vein thrombosis (DVT) and the molecular mechanisms, involved in its pathophysiology, needs further investigations. In the present study, C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1β), matrix metalloproteases-9 (MMP-9), vascular endothelial growth factor (VEGF), tissue factor (TF), fibrinogen and soluble P-selectin, were analyzed in plasma and in monocyte samples from 385 cancer patients, of whom 64 were concomitantly affected by DVT (+). All these markers were higher in cancer patients DVT+ than in those DVT-. Accordingly, significantly higher NF-kB activity was observed in cancer patients DVT+ than DVT-. Significant correlation between data obtained in plasma and monocyte samples was observed. NF-kB inhibition was associated with decreased levels of all molecules in both cancer DVT+ and DVT-. To further demonstrate the involvement of NF-kB activation by the above mentioned molecules, we treated monocyte derived from healthy donors with a pool of sera from cancer patients with and without DVT. These set of experiments further suggest the significant role played by some molecules, regulated by NF-kB, and detected in cancer patients with DVT. Our data support the notion that NF-kB may be considered as a therapeutic target for cancer patients, especially those complicated by DVT. Treatment with NF-kB inhibitors may represent a possible strategy to prevent or reduce the risk of DVT in cancer patients.

NGC 1068 is a nearby, widely studied Seyfert II galaxy presenting radio, infrared, X-ray, and γ-ray emission, along with strong evidence for high-energy neutrino emission. Recently, the evidence for neutrino emission was explained in a multimessenger model, whereby the neutrinos originate from the corona of the active galactic nucleus. In this environment, γ-rays are strongly absorbed, so that an additional contribution is necessary, for instance, from the circumnuclear starburst ring. In this work, we discuss whether the radio jet can be an alternative source of the γ-rays between about 0.1 and 100 GeV, as observed by Fermi-LAT. In particular, we include both leptonic and hadronic processes, namely, accounting for inverse Compton emission and signatures from pp as well as pγ interactions. In order to constrain our calculations, we used VLBA and ALMA observations of the radio knot structures, which are spatially resolved at different distances from the supermassive black hole. Our results show that the best leptonic scenario for the prediction of the Fermi-LAT data is provided by the radio knot closest to the central engine. For that to be the case, a magnetic field strength of ∼1 mG is needed as well as a strong spectral softening of the relativistic electron distribution at (1 − 10) GeV. However, we show that neither such a weak magnetic field strength, nor such a strong softening is expected for that knot. A possible explanation for the ∼10 GeV γ-rays could potentially be provided by hadronic pion production in case of a gas density ≳104 cm−3. Nonetheless, this process is not found to contribute significantly to the low-energy end of the Fermi-LAT range. We conclude that the emission sites in the jet are not sufficient to explain the γ-rays across the whole Fermi-LAT energy band. [ABSTRACT FROM AUTHOR]

A variety of good management practices have been recommended to minimize the impact of water runoff from production nurseries. However, studies have not been conducted to gauge which management practices nursery producers are most likely to adopt in response to education and increased government oversight. We surveyed 85 production nurseries in Southern California about their existing practices to limit the impacts of runoff from their facilities. Of these, 65 in Ventura County were resurveyed with the same questionnaire within 2 years. The positive response rate for following good management practices was 65%, compared to 57% in the initial survey. There were significant increases in every category of practices surveyed, and significant changes in the adoption of 38 specific practices. This suggests that nurseries are amenable to adopting management practices within a short time span in areas where there is increased governmental oversight and educational opportunities for growers.

Objective: This study aimed to evaluate histological modifications of the vaginal mucosa after repeated microablative fractional CO2 laser treatments. As secondary objectives we evaluated the clinical effects associated with repeated microablative fractional CO2 laser treatments using validated questionnaires. Methods: A prospective intervention study was performed in the Division of Gynecology and Obstetrics, Urogynecology Unit, IRCCS San Raffaele Scientific Institute with 15 postmenopausal women complaining of genitourinary syndrome of menopause symptoms. The cohort of patients was submitted to at least two previous laser treatment cycles in the past years. The Vaginal Health Index (VHI), visual analog scale (VAS), Female Sexual Function Index (FSFI), Urinary Distress Inventory-6 (UDI-6), International Consultation on Incontinence Questionnaire – Urinary Incontinence (ICIQ-UI) and 5-point Likert scale were used. Moreover, histological examinations were carried out on all samples. Results: At 4weeks after the last treatment, the VHI score and all FSFI items were significantly increased compared with baseline. We observed a statistically significant decrease in both frequency and severity for all urinary symptoms after the follow-up. We observed a statistically significant increase in the number of epithelial cell layers with a consequent increase in epithelial thickness, in the number of glycogen-filled cells and in the number of papillae after the laser treatment. No signs of fibrosis were observed as neovascularization was observed in each woman. Conclusions: This is the first study demonstrating the histological persistency of efficacy in repeated annually laser treatment cycles, with tissue changes always leading to regenerative results without any sign of fibrosis. [ABSTRACT FROM AUTHOR]

The paper tests longitudinally the hypothesis that educational subcultures in terms of which students interpret their role and their educational setting affect the probability of dropping out of higher education. A logistic regression model was performed to predict drop out at the beginning of the second academic year for the 823 freshmen of a three-year bachelor degree in psychology at an Italian university. The model uses both measures of students' educational subculture and incoming levels of knowledge and skills. The probability of dropping out was used as dependent variable. Results show that the probability of dropping out is significantly associated with students' educational subculture--but not with their incoming level of knowledge and skills. Our results suggest the need to recognize the meaning as a legitimate variable of research and of intervention in the field of educational success.

In this manuscript, the concept of an orthogonal intuitionistic fuzzy b-metric space is initiated as a generalization of an intuitionistic fuzzy b-metric space. We presented some fixed point results in this setting. For the validity of the obtained results, some non-trivial examples are given. In the last part, we established an application on the existence of a unique solution of a Fredholm-type integral equation.

The study aimed to test if Briganti’s 2012 nomogram could be associated with the risk of prostate cancer (PCa) progression in European Association of Urology (EAU) intermediate-risk patients treated with robotic surgery. From January 2013 to December 2021, 527 consecutive patients belonging to the EAU intermediate-risk class were selected. Briganti’s 2012 nomogram, which predicts the risk of pelvic lymph node invasion (PLNI), was assessed as a continuous and dichotomous variable that categorized up to the median of 3.0%. Disease progression defined as biochemical recurrence and/or metastatic progression was evaluated by Cox proportional hazards (univariate and multivariate analysis). After a median follow-up of 95.0 months (95% confidence interval [CI]: 78.5–111.4), PCa progression occurred in 108 (20.5%) patients who were more likely to present with an unfavorable nomogram risk score, independently by the occurrence of unfavorable pathology including tumor upgrading and upstaging as well as PLNI. Accordingly, as Briganti’s 2012 risk score increased, patients were more likely to experience disease progression (hazard ratio [HR] = 1.060; 95% CI: 1.021–1.100; P = 0.002); moreover, it also remained significant when dichotomized above a risk score of 3.0% (HR = 2.052; 95% CI: 1.298–3.243; P < 0.0001) after adjustment for clinical factors. In the studied risk population, PCa progression was independently predicted by Briganti’s 2012 nomogram. Specifically, we found that patients were more likely to experience disease progression as their risk score increased. Because of the significant association between risk score and tumor behavior, the nomogram can further stratify intermediate-risk PCa patients, who represent a heterogeneous risk category for which different treatment paradigms exist.

The digital age introduced the Digital Ecological Niche (DEN), revolutionizing human interactions. The advent of Digital History (DHy) has marked a methodological shift in historical studies, tracing its roots to Babbage and Lovelace’s 19th-century work on “coding” as a foundational communication process, fostering a new interaction paradigm between humans and machines, termed “person2persons2machines.” This evolution, through digitization and informatization, builds upon ancient coding practices but was significantly advanced by Babbage and Lovelace’s contributions to mathematical linguistic systems, laying the groundwork for Computer Science. This field, central to 20th-century mainframe interaction through programming languages and formalization, situates Digital History within a broader historical context. Here, coding and mathematical methodologies empower historians with advanced technologies for historical data preservation and analysis. Nonetheless, the extent to which computation and Turing machines can fully understand and interpret history remains a subject of debate.

Abstract The synthetic lethal effect observed with the use of PARP inhibitors (PARPi) with tumors characterized by the loss of key players in the homologous recombination (HR) pathway, commonly referred to as “BRCAness”, is maintaining high interest in oncology. While BRCAness is a well-established feature in breast, ovarian, prostate, and pancreatic carcinomas, our recent findings indicate that up to 15% of colorectal cancers (CRC) also harbor defects in the HR pathway, presenting promising opportunities for innovative therapeutic strategies in CRC patients. We developed a new tool called HRDirect, which builds upon the HRDetect algorithm and is able to predict HR deficiency (HRD) from reference-free tumor samples. We validated HRDirect using matched breast cancer and CRC patient samples. Subsequently, we assessed its efficacy in predicting response to the PARP inhibitor olaparib by comparing it with two other commercial assays: AmoyDx HRD by Amoy Diagnostics and the TruSight Oncology 500 HRD (TSO500-HRD) panel by Illumina NGS technology. While all three approaches successfully identified the most PARPi-sensitive CRC models, HRDirect demonstrated superior precision in distinguishing resistant models compared to AmoyDX and TSO500-HRD, which exhibited overlapping scores between sensitive and resistant cells. Furthermore, we propose integrating HRDirect scoring with ATM and RAD51C immunohistochemical analysis as part of our “composite biomarker approach” to enhance the identification of HRD tumors, with an immediate translational and clinical impact for CRC personalized treatment.

Abstract Broadband Coherent anti-Stokes Raman (BCARS) microscopy is an imaging technique that can acquire full Raman spectra (400–3200 cm−1) of biological samples within a few milliseconds. However, the CARS signal suffers from an undesired non-resonant background (NRB), deriving from four-wave-mixing processes, which distorts the peak line shapes and reduces the chemical contrast. Traditionally, the NRB is removed using numerical algorithms that require expert users and knowledge of the NRB spectral profile. Recently, deep-learning models proved to be powerful tools for unsupervised automation and acceleration of NRB removal. Here, we thoroughly review the existing NRB removal deep-learning models (SpecNet, VECTOR, LSTM, Bi-LSTM) and present two novel architectures. The first one combines convolutional layers with Gated Recurrent Units (CNN + GRU); the second one is a Generative Adversarial Network (GAN) that trains an encoder-decoder network and an adversarial convolutional neural network. We also introduce an improved training dataset, generalized on different BCARS experimental configurations. We compare the performances of all these networks on test and experimental data, using them in the pipeline for spectral unmixing of BCARS images. Our analyses show that CNN + GRU and VECTOR are the networks giving the highest accuracy, GAN is the one that predicts the highest number of true positive peaks in experimental data, whereas GAN and VECTOR are the most suitable ones for real-time processing of BCARS images.

Abstract There is increasing interest in the pathophysiological role of arginine metabolism in schizophrenia, particularly in relation to the modulation of the endogenous messenger nitric oxide (NO). The assessment of specific arginine metabolites that, unlike NO, are stable can provide useful insights into NO regulatory enzymes such as isoform 1 of dimethylarginine dimethylaminohydrolase (DDAH1) and arginase. We investigated the role of arginine metabolomics in schizophrenia by conducting a systematic review and meta-analysis of the circulating concentrations of arginine metabolites associated with DDAH1, arginase, and NO synthesis [arginine, citrulline, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), dimethylamine, and ornithine] in this patient group. We searched PubMed, Scopus, and Web of Science from inception to the 31st of May 2023 for studies investigating arginine metabolites in patients with schizophrenia and healthy controls. The JBI Critical Appraisal Checklist for analytical studies and GRADE were used to assess the risk of bias and the certainty of evidence, respectively (PROSPERO registration number: CRD42023433000). Twenty-one studies were identified for analysis. There were no significant between-group differences in arginine, citrulline, and SDMA. By contrast, patients with schizophrenia had significantly higher ADMA (DDAH1 substrate, standard mean difference, SMD = 1.23, 95% CI 0.86–1.61, p

Abstract Aims A set of indicators to assess the quality of care for patients hospitalized for heart failure was developed by an expert working group of the Italian Health Ministry. Because a better performance profile measured using these indicators does not necessarily translate to better outcomes, a study to validate these indicators through their relationship with measurable clinical outcomes and healthcare costs supported by the Italian National Health System was carried out. Methods and results Residents of four Italian regions (Lombardy, Marche, Lazio, and Sicily) who were newly hospitalized for heart failure (irrespective of stage and New York Heart Association class) during 2014–2015 entered in the cohort and followed up until 2019. Adherence to evidence‐based recommendations [i.e. renin–angiotensin–aldosterone system (RAS) inhibitors, beta‐blockers, mineralocorticoid receptor antagonists (MRAs), and echocardiograms (ECCs)] experienced during the first year after index discharge was assessed. Composite clinical outcomes (cardiovascular hospital admissions and all‐cause mortality) and healthcare costs (hospitalizations, drugs, and outpatient services) were assessed during the follow‐up. The restricted mean survival time at 5 years (denoted as the number of months free from clinical outcomes), the hazard of clinical outcomes (according to the Cox model), and average annual healthcare cost (expressed in euros per person‐year) were compared between adherent and non‐adherent patients. A non‐parametric bootstrap method based on 1000 resamples was used to account for uncertainty in cost‐effectiveness estimates. A total of 41 406 patients were included in this study (46.3% males, mean age 76.9 ± 9.4 years). Adherence to RAS inhibitors, beta‐blockers, MRAs, and ECCs were 64%, 57%, 62%, and 20% among the cohort members, respectively. Compared with non‐adherent patients, those who adhered to ECCs, RAS inhibitors, beta‐blockers, and MRAs experienced (i) a delay in the composite outcome of 1.6, 1.9, 1.6, and 0.6 months and reduced risks of 9% (95% confidence interval, 2–14%), 11% (7–14%), 8% (5–11%), and 4% (−1–8%), respectively; and (ii) lower (€262, €92, and €571 per year for RAS inhibitors, beta‐blockers, and MRAs, respectively) and higher costs (€511 per year for ECC). Adherence to RAS inhibitors, beta‐blockers, and MRAs showed a delay in the composite outcome and a saving of costs in 98%, 84%, and 93% of the 1000 bootstrap replications, respectively. Conclusions Strict monitoring of patients with heart failure through regular clinical examinations and drug therapies should be considered the cornerstone of national guidelines and audits.

Nuclear magnetic resonance (NMR) is a technique used for many years by chemists for elucidation of molecular structure. Technological progress over the years has enabled this technique, making it easier to use. Thus, the LF-NMR (low-field NMR) was introduced as a side technique, characterized by low management costs and shorter analysis time than its main counterpart. The application of 1H LF-NMR for the quantification of ethyl alcohol in different alcoholic matrices is herein described, comparing the results obtained with this technique with those determined by a reference gas chromatographic method.