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Abstract Background Children and adolescents’ physical inactivity is a global problem. Financial incentives are increasingly utilised to support children’s participation in sport, with programs introduced in multiple jurisdictions globally, however few programs have comprehensive evaluations. This study used a Delphi methodology to develop evaluation recommendations for an existing population-wide financial incentive program based in South Australia. Methods A three-round Delphi study was conducted from October 2022 to April 2023. A diverse range of stakeholders including end-users, government representatives, academics/researchers, and Non-Government Organisation representatives participated in the Delphi panel. Round 1 focussed on the perceived importance of various evaluation components, including reach, process, and effectiveness. Round 2 focussed on identifying evaluation approaches and tools, while Round 3 determined methodological priorities and timeframes. A consensus level of ≥ 70% was set a priori (rating 6 or 7 on 7-point scale). Round 3 results were used to formulate evaluation recommendations. Results Sixty-seven stakeholders agreed to participate, with an average response rate of 76% (87%; 73% and 67% for each round, respectively). All evaluation components gained consensus in Round 1. In Round 2, consensus was gained on 14 evaluation measures, including measuring the cost of sport, awareness of the program amongst eligible families, and reasons for non-participation, with evaluation methods generated for each measure. Round 3 results determined participants’ preferred methods of evaluation and informed the development of evaluation recommendations. Recommended evaluation methods included mixed method approaches for provider and user process evaluations and measuring program awareness using an epidemiological survey. Conclusion This Delphi study sought the views and opinions from diverse stakeholders to create evaluation recommendations for a population-wide sports voucher program. Results suggested that a comprehensive evaluation strategy is needed to understand the reach, effectiveness, and impact of the program. Additionally, there was a consensus on reallocating program funds for this evaluation.

Abstract Extracellular vesicles (EVs) are a new mechanism of cellular communication, by delivering their cargo into target cells to modulate molecular pathways. EV-mediated crosstalk contributes to tumor survival and resistance to cellular stress. However, the role of EVs in B-cell Acute Lymphoblastic Leukaemia (B-ALL) awaits to be thoroughly investigated. We recently published that ActivinA increases intracellular calcium levels and promotes actin polymerization in B-ALL cells. These biological processes guide cytoskeleton reorganization, which is a crucial event for EV secretion and internalization. Hence, we investigated the role of EVs in the context of B-ALL and the impact of ActivinA on this phenomenon. We demonstrated that leukemic cells release a higher number of EVs in response to ActivinA treatment, and they can actively uptake EVs released by other B-ALL cells. Under culture-induced stress conditions, EVs coculture promoted cell survival in B-ALL cells in a dose-dependent manner. Direct stimulation of B-ALL cells with ActivinA or with EVs isolated from ActivinA-stimulated cells was even more effective in preventing cell death. This effect can be possibly ascribed to the increase of vesiculation and modifications of EV-associated microRNAs induced by ActivinA. These data demonstrate that ActivinA boosts EV-mediated B-ALL crosstalk, improving leukemia survival in stress conditions.

Asparagine (Asn) deamidation and aspartic acid (Asp) isomerization are common degradation pathways that affect the stability of therapeutic antibodies. These modifications can pose a significant challenge in the development of biopharmaceuticals. As such, the early engineering and selection of chemically stable monoclonal antibodies (mAbs) can substantially mitigate the risk of subsequent failure. In this study, we introduce a novel in silico approach for predicting deamidation and isomerization sites in therapeutic antibodies by analyzing the structural environment surrounding asparagine and aspartate residues. The resulting quantitative structure-activity relationship (QSAR) model was trained using previously published forced degradation data from 57 clinical-stage mAbs. The predictive accuracy of the model was evaluated for four different states of the protein structure: (1) static homology models, (2) enhancing low-frequency vibrational modes during short molecular dynamics (MD) runs, (3) a combination of (2) with a protonation state reassignment, and (4) conventional full-atomistic MD simulations. The most effective QSAR model considered the accessible surface area (ASA) of the residue, the pKa value of the backbone amide, and the root mean square deviations of both the alpha carbon and the side chain. The accuracy was further enhanced by incorporating the QSAR model into a decision tree, which also includes empirical information about the sequential successor and the position in the protein. The resulting model has been implemented as a plugin named “Forecasting Reactivity of Isomerization and Deamidation in Antibodies” in MOE software, completed with a user-friendly graphical interface to facilitate its use.

The purpose of this paper is to analyse the role of natural translation in heritage speakers’ bilingual communication in relation to the family language policies (FLP) adopted to maintain heritage language in Italian and German multilingual families. In order to investigate this, in spring 2023, a semi-structured questionnaire was administered to both parents and children. The sample consists of 60 Russian-speaking bilingual HS living in Italy and Germany, where they have access to regular primary education and attend, in some cases, private Russian courses or schools. The informants do not receive specific translation training from or into the Russian language (they only practice translation at school from or into Italian/German), and they translate, in most cases, as an occasional activity, closer to the function of mediation or brokering. The role of translation in relation to FLP seems particularly relevant when comparing the two samples, considering different family compositions: mostly bi-ethnic in Italy and mono-ethnic in Germany. The survey showed that in daily life, both parents and children use translation, often as a specific kind of bilingual communication. In the Italian part of the sample, the strategy called OPOL prevails, and translation is a frequent activity in the domestic sphere. In the German one, instead, the separation of language use contexts is widespread, and all family members speak both Russian and German, making translation activity less relevant.

Abstract Grid integration constraints are limiting the deployment potential of renewable energy sources in Malta. Large penetrations of photovoltaics in the low voltage (LV) distribution network pose a significant risk to grid stability due to their inherent intermittency and are known to cause overvoltages and reverse power flows. The authors evaluate how self‐consumption strategies with distributed battery energy storage systems can contribute to the voltage regulation in LV networks and the reduction of reverse power flows. The batteries are controlled to absorb the reverse power flow at the dwellings' point of common coupling, before this is injected into the LV network. Simulations show that uncoordinated strategies are not suitable to address the distribution network challenges during reverse power flows and evening peak demands. On the other hand, self‐consumption coordinated by a time‐varying feed‐in tariff (FiT) can provide higher profitability to the prosumers while providing added benefits to the utility. The net‐billing profitability for the prosumers in a self‐consumption scenario with time‐varying FiT is transformed from the downward trend of the uncoordinated scenario to an upward trend against the increasing values of storage capacity.

Abstract Short-acting bronchodilators are a class of medications commonly used to treat asthma, chronic obstructive pulmonary disease, and other respiratory conditions. The use of these medications has evolved over time as we have gained a better understanding of their effectiveness and safety in the pediatric population. This comprehensive review synthesizes the current understanding of short-acting β2-agonists and short-acting anticholinergics in children. It addresses indications, contraindications, safety considerations, and highlights areas where further research is needed to guide the most effective use of short-acting bronchodilators.

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Background: Prostate cancer (PCa) management is moving towards patient-tailored strategies. Advances in molecular and genetic profiling of tumor tissues, integrated with clinical risk assessments, provide deeper insights into disease aggressiveness. This study aims to offer a comprehensive overview of the pivotal genomic tests supporting PCa treatment decisions, analyzing—through real-world data—trends in their use and the growth of supporting literature evidence. Methods: A retrospective analysis was conducted using the extensive PearlDiver™ Mariner database, which contains de-identified patient records, in compliance with the Health Insurance Portability and Accountability Act (HIPAA). The International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes were employed to identify patients diagnosed with PCa during the study period—2011 to 2021. We determined the utilization of primary tissue-based genetic tests (Oncocyte DX®, Prolaris®, Decipher®, and ProMark®) across all patients diagnosed with PCa. Subsequently, within the overall PCa cohort, patients who underwent radical prostatectomy (RP) and received genetic testing postoperatively were identified. The yearly distribution of these tests and the corresponding trends were illustrated with graphs. Results: During the study period, 1,561,203 patients with a PCa diagnosis were recorded. Of these, 20,748 underwent tissue-based genetic testing following diagnosis, representing 1.3% of the total cohort. An increasing trend was observed in the use of all genetic tests. Linear regression analysis showed a statistically significant increase over time in the use of individual tests (all p-values < 0.05). Among the patients who underwent RP, 3076 received genetic analysis following surgery, representing 1.27% of this group. Conclusions: Our analysis indicates a growing trend in the utilization of tissue-based genomic testing for PCa. Nevertheless, they are utilized in less than 2% of PCa patients, whether at initial diagnosis or after surgical treatment. Although it is anticipated that their use may increase as more scientific evidence becomes available, their role requires further elucidation.

Abstract Solar photovoltaics in Malta have increased substantially over the years, both at large scale and residential scale. The present installed capacity is already having a negative impact on Malta's’ grid infrastructure, causing problems due to the reverse power flows (resulting from oversupply) and related issues such as voltage rise. This paper considers the integration of a low voltage regulator in a low voltage feeder in a semi‐rural area in Malta. A thyristor‐controlled transformer‐based low voltage regulator was modelled and simulated in MATLAB/Simulink using the PLECS blockset. Experimental results were also obtained via measurements of the voltage profiles at 70% of the actual low voltage feeder that showed several instances of over and under voltage events. The outputs obtained from the simulation model strongly agreed with those obtained from the field testing thereby validating the simulation models that were developed in this study. Results show that the voltage on the feeder was successfully regulated to around the nominal voltage of 240 V. The regulator failed to correct the voltage to within ±10% in one occurrence where the load demand and hence the voltage drop was too high.

Abstract Notifications of invasive group A streptococcal (iGAS) infections have significantly increased in many European Countries compared to the previous season. In Italy, there has been an increase in streptococcal pharyngitis and scarlet fever cases since January 2023, which sparked concerns about a GAS epidemic in the pediatric population. This rise may be ascribed to the GAS infection season that began earlier than usual (off-season outbreak) and the increase in the spread of respiratory viruses and viral coinfections that raised the risk of iGAS disease. Moreover, this phenomenon was also facilitated by increased travel after reduced GAS circulation during the COVID-19 pandemic. The increase in cases of GAS disease has raised some critical issues regarding the potential reactions to administering amoxicillin, the first-line antibiotic therapy, many of which have been erroneously labeled as “allergy." For these reasons, the Italian Society of Pediatric Allergy and Immunology (SIAIP) intends to provide simple clinical indications to help pediatricians manage GAS pharyngitis, discerning the allergic from non-allergic drug hypersensitivity.

Single-port (SP) robotic surgery is a relatively new technology that is expected to become available on the European market within a year. We investigated the current expectations of robotic surgery experts and opinion leaders practicing in Europe. A 17-item online questionnaire was sent to 120 participants identified as “experts” on the basis of their general contributions to the field of robotic surgery. Overall, 90 responses were registered, with a response rate of 75%. Italy (30%), France (15%), and the UK (12%) provided the most participants, who worked mainly in academic—either public (60%) or private (20%)—hospitals. Most respondents (79%) had no previous experience with “single site” surgery, and attendance at scientific meetings (79%) and perusal of the literature (65%) were the sources of SP knowledge most frequently reported. The perceived advantages of SP robotic surgery included lower invasiveness (61%), easier access to the retroperitoneal or extraperitoneal space (53%), better cosmetic results (44%), and lower postoperative pain (44%). The most “appealing” SP procedures were retroperitoneal partial nephrectomy via an anterior approach (43%) and transvesical simple prostatectomy (43%). Within the limitations of this type of analysis, our findings suggest high interest and a positive attitude towards SP technology overall. Patient summary: Technology for single-port (SP) robotic surgery, in which just one skin incision is made in the abdomen to perform the operation, will soon be available in Europe. We conducted a survey on SP surgery among European experts in urological robotic surgery. The results show that there is high interest in and a positive attitude to SP surgery. The SP approach could result in better cosmetic results and lower postoperative pain for patients.

Chronic sinusitis (CS) is characterized by sinonasal inflammation, mucus overproduction, and edematous mucosal tissue. CS impacts one in seven adults and estimates suggest up to 15% of the general U.S. population may be affected. This research sought to assess a potential role for receptors for advanced glycation end-products (RAGE), an inflammatory receptor expressed in tissues exposed to secondhand smoke (SHS). Human sinus tissue sections were stained for RAGE and S100s, common RAGE ligands. Wild-type mice and mice that over-express RAGE in sinonasal epithelium (RAGE TG) were maintained in room air (RA) or exposed to secondhand smoke (SHS) via a nose-only delivery system five days a week for 6 weeks. Mouse sections were stained for RAGE and tissue lysates were assayed for cleaved caspase 3, cytokines, or matrix metalloproteases. We discovered increased RAGE expression in sinus tissue following SHS exposure and in sinuses from RAGE TG mice in the absence of SHS. Cleaved caspase-3, cytokines (IL-1β, IL-3, and TNF-α), and MMPs (-9 and -13) were induced by SHS and in tissues from RAGE TG mice. These results expand the inflammatory role of RAGE signaling, a key axis in disease progression observed in smokers. In this relatively unexplored area, enhanced understanding of RAGE signaling during voluntary and involuntary smoking may help to elucidate potential therapeutic targets that may attenuate the progression of smoke-related CS.

Objective: This video aims to demonstrate the safety and feasibility of performing deferred cytoreductive nephrectomy (dCN) using robotic assistance in patient treated with immunotherapy for metastatic renal cell carcinoma (mRCC). Patients and surgical procedure: A 62-year-old woman, affected by right metastatic renal cell carcinoma, showed partial response after 4 cycles of Pembrolizumab and Axitinib. Multidisciplinary team consultation decided for cytoreductive right radical nephrectomy with adrenalectomy. After anatomical landmarks identification, inferior vena cava (IVC) was progressively exposed, until identifying the renal hilum. During surgery, small bleeding occurred, and Weck-clips were placed to control the arterial flow. Nephrectomy proceeded without complications. Right adrenal gland, suspected of metastasis, was removed. Results: No intra- and post-operative high-grade Clavien-Dindo complications occurred, and the patient was discharged in post-operative day 3. Final pathology revealed clear cell renal cell carcinoma with sarcomatoid features, Furhman grade 4, with metastatic lesion in the omolateral adrenal gland (pT3a pM1) Conclusion: Robot-assisted dCN is feasible and safe after immune checkpoint inhibitor-based combination therapy in patients affected by mRCC.

This study aimed to explore the rates of motor difficulties in children from the Australian Autism Biobank, and how early motor concerns impacted on children functionally. Children with autism aged 2-7 years, including 441 with a Vineland Adaptive Behavior Scale (VABS-II) motor subscale and 385 with a Mullen Scales of Early Learning (MSEL) fine motor subscale were included (n total = 514; 80% male). Approximately 60% of children on the MSEL and ~ 25% on the VABS-II had clinically significant motor impairments. More children with delayed sitting and walking motor milestones had early childhood parent reported motor difficulties (p < 0.001). Early motor delays or concerns may assist identifying individuals who will likely benefit from early ongoing developmental monitoring and early support.

Il numero che si propone mette in evidenza diversi posizionamenti della ricerca antropologica sul campo. In questa direzione, la nota, che potete leggere di seguito, riprende alcuni punti salienti di un processo che viene definito etnografia della ricerca sul campo. Di seguito, troviamo, una presentazione storica e una più corposa riflessione di ordine teorico-metodologico che affronteranno questo tema. Sarà ripreso brevemente il percorso storico che ha portato a strutturare le tecniche della ricerca etnografica, per approdare poi ad alcuni antropologi contemporanei che hanno perfezionato e potenziato lo strumento di ricerca ampliando così la gamma di tecniche a disposizione del ricercatore sul campo.

Il numero che proponiamo affronta temi e riflessioni che si pongono l’obiettivo d’indagare problematiche legate allo sviluppo dell’identità, personale e professionale, degli adolescenti. Le ricerche proposte si muovono dentro le cornici teoriche e metodologiche dell’antropologia applicata e della psico-pedagogia. Come ormai sappiamo, l’adolescenza è un periodo evolutivo assai travagliato, che è caratterizzata anche per il modificarsi continuo di un corpo che tende verso il compimento del suo sviluppo e la sua maturità psico-emotiva.

Abstract Background Acquisition of psychomotor skills is of utmost importance for competent preclinical restorative dentistry. Recent advancements in haptic feedback technology have been incorporated into preclinical dental education to augment the conventional phantom head-based training. Objective This systematic review aims to assess the effectiveness of haptic feedback device, Simodont, in improving the skill development and learning outcomes of dental students during their preclinical training. Materials and methods Electronic databases Web of Science, Scopus, PubMed were searched for relevant studies since inception up until March, 2023. Only English language studies that assessed the effectiveness of haptic feedback devices in preclinical dental education were included. We excluded studies that did not use Simodont as the haptic feedback device or did not involve preclinical restorative work. Study quality was assessed using the revised Cochrane risk of bias tool and ROBINS-I. The primary goal of the study is to evaluate the efficacy of Simodont as a complementary training modality for dentistry students. Results Results from 9 high-quality studies were analyzed and synthesized to evaluate the overall impact of haptic feedback devices on various aspects of preclinical training. The studies were conducted on 826 undergraduate dental students enrolled in various years of their training across dental colleges and universities in different parts of the world. A majority of studies showed some concerns regarding risk of bias. Haptic feedback devices added a new layer to Virtual Reality (VR) through the perception of touch and force feedback. It assisted junior dental students improve their psychomotor skills and movement skills. Instantaneous feedback on the students' performance helped enhance their self-assessment and correction, and also eliminated the subjectivity of evaluation. Data derived from virtual simulators helped stratify dental students and predict their clinical performance, providing an opportunity to tailor the learning process to meet individual diversity in students' expertise. Conclusion Based on the limited evidence available, Simodont was effective in preclinical training of dental students, offering advantages such as unlimited reproducibility, objective evaluation of preparation by computer assessment, and cost reduction. And further studies are warranted to explore the incorporation of patient's oral environment simulation for better skill training.

Currently, there are a few detailed guidelines on the overall management of children and adolescents with moderate-severe atopic dermatitis. AD ​​is a complex disease presenting with different clinical phenotypes, which require an individualized and multidisciplinary approach. Therefore, appropriate interaction between primary care pediatricians, pediatric allergists, and pediatric dermatologists is crucial to finding the best management strategy. In this manuscript, members of the Italian Society of Pediatric Allergology and Immunology (SIAIP), the Italian Society of Pediatric Dermatology (SIDerP), and the Italian Society of Pediatrics (SIP) with expertise in the management of moderate-severe atopic dermatitis have reviewed the latest scientific evidence in the field. This narrative review aims to define a pathway to appropriately managing children and adolescents with moderate-severe atopic dermatitis.

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren's syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

Participant recruitment is one of the most challenging aspects of a clinical trial, directly impacting both the study’s duration and the quality of its results. Therefore, reporting successful recruitment strategies is crucial. This study aimed to document the recruitment tactics and experiences of a research team during a university-based randomized clinical trial, conducted as part of a clinical research immersion program. Recruitment took place from October 2021 to October 2022. Before the study commenced, study team members received formal training in clinical trial participant recruitment from the Principal Investigator. The recruitment strategies were integrated into initial study design, which was approved by the Institutional Review Board. A multimodal approach was employed, incorporating both direct and indirect recruitment methods. These strategies successfully met the enrollment target within the twelve-month period. Throughout the process, team members acquired valuable knowledge in recruitment design and implementation, along with transferable interpersonal and networking skills. In-person recruitment was the most efficient and cost-effective strategy, followed by personal referrals. The primary challenge was accommodating participants’ availability. Other study teams should consider these recruitment strategies during their study designs. Additionally, the knowledge and skills gained by this study team underscore the value of experiential learning in research education.

The aim of our study is to evaluate the effectiveness and safety of a sutureless off-clamp robot-assisted partial nephrectomy (sl-oc RAPN), particularly its impact on renal function. A multicenter study was conducted from April 2021 to June 2022. Patients diagnosed with a renal mass of >2 cm and a PADUA score of ≤6 consecutively underwent an sl-oc RAPN procedure. Tumor features, patients characteristics, and intraoperative outcomes were assessed. An evaluation of renal function was performed preoperatively, and again at 1 and 3 months after surgery by measuring the creatinine and blood urea nitrogen levels. The renal function of the two separate kidneys was assessed by a sequential renal scintigraphy performed before and at least 30 days after surgery. A total of 21 patients underwent an sl-oc RAPN. The median age was 64 years (IQR 52/70), the median tumor diameter was 40 mm (IQR 29/45), and the median PADUA score was 4 (3.5/5). The intraoperative outcomes included operative time (OT), 90 (IQR 74/100) min; estimated blood loss (EBL), 150 (IQR 50/300) mL; and perioperative complications, CD > 3 1(5%); only two patients presented positive surgical margins in their final histology (2/21, 10%). Compared to the preoperative value, a decrease in renal function was highlighted with a statistically significant median decrease of 10 mL/min (p < 0.01). The renal scintigraphy showed an overall decrease in renal function compared to the preoperative value, with a range in the operated kidney that varied from 0 to 15 mL/s and from 0% to 40%, with a median value of 4 mL/s and 12%. sl-oc RAPN is a safe procedure, with a minimal impact on kidney function alteration. This technique has proven effective in preserving renal function and maintaining optimal oncological outcomes with limited complications.

Introduction: Artificial intelligence (AI) tools are increasingly being integrated into computer-aided diagnosis systems that can be applied to improve the recognition and clinical and molecular characterization of allergic diseases, including eosinophilic esophagitis (EoE). This review aims to systematically evaluate current applications of AI, machine learning (ML), and deep learning (DL) methods in EoE characterization and management. Methods: We conducted a systematic review using a registered protocol published in the International Prospective Register of Systematic Reviews (CRD42023451048). The risk of bias and applicability of eligible studies were assessed according to the prediction model study risk of bias assessment tool (PROBAST). We searched PubMed, Embase, and Web of Science to retrieve the articles. The literature review was performed in May 2023. We included original research articles (retrospective or prospective studies) published in English in peer-reviewed journals, studies whose participants were patients with EoE, and studies assessing the application of AI, ML, or DL models. Results: A total of 120 articles were found. After removing 68 duplicates, 52 articles were reviewed based on the title and abstract, and 34 were excluded. Eleven full texts were assessed for eligibility, met the inclusion criteria, and were analyzed for the systematic review. The AI models developed in three studies for identifying EoE based on endoscopic images showed high score performance with an accuracy that ranged from 0.92 to 0.97. Five studies developed AI models that histologically identified EoE with high accuracy (87% to 99%). We also found two studies where the AI model identified subgroups of patients according to their clinical and molecular features. Conclusions: AI technologies could promote more accurate evidence-based management of EoE by integrating the results of molecular signature, clinical, histology, and endoscopic features. However, the era of AI application in medicine is just beginning; therefore, further studies with model validation in the real-world environment are required.

Severe asthma (SA) is still a demanding challenge in clinical practice. Type 2 inflammation is the most common phenotype in children and adolescents with SA. As a result, anti-inflammatory drugs, mainly corticosteroids (CSs), represent the first choice to reduce type 2 inflammation. However, SA patients may require high inhaled and oral CS doses to achieve and maintain asthma control. Some SA patients, despite the highest CS dosages, can even display uncontrolled asthma. Therefore, the biological era constituted a breakthrough in managing this condition. Dupilumab is a monoclonal antibody directed against the IL-4 receptor α-subunit (IL-4Rα), antagonizing against both IL-4 and IL-13, and has been approved for pediatric severe type 2 asthma. This review presents and discusses the most recent published studies on dupilumab in children and adolescents with SA. There is convincing evidence that dupilumab is a safe and effective option in managing SA as it can reduce asthma exacerbations, reduce CS use, and improve lung function, asthma control, and quality of life, also for caregivers. However, a thorough diagnostic pathway is mandatory, mainly concerning phenotyping. In fact, the ideal eligible candidate is a child or adolescent with a type 2 allergic phenotype.

Abstract Background Diagnosing central precocious puberty (CPP) requires an integrated approach based on clinical, biochemical and instrumental data. The diagnostic gold standard is represented by GnRH (gonadotropin-releasing hormone) stimulation test. Some undoubted limitations of this procedure led the international scientific community to look for cheaper and less invasive alternative diagnostic methods, such as luteinizing hormone urinary levels (uLH) measurement. This study aims to define the reliability of urinary LH levels as a biomarker of pubertal development, both concerning the initial diagnostic management and the monitoring of patients with central precocious puberty undergoing therapy with GnRH analogues. Furthermore, the study plans to detect the potential association between LH peak serum (pLH) and urinary LH in patients undergoing diagnostic tests with GnRH and to identify a possible cut-off of uLH that may be suggestive of ensued successful hormonal stimulation. Methods The study includes 130 female patients with suspected precocious puberty or in follow-up during suppressive therapy. After the collection of the informed consent, the patients underwent clinical evaluation, auxological assessment, and hormone assays (basal levels of LH, FSH, and oestradiol; GnRH stimulating test in patients with suspected precocious puberty; urinary LH assay on the first-morning urine sample, collected after waking up). Results Two uLH cut-off values have been identified: the first of 0.25 UI/L [C.I. 95% 0.23–0.27], able to distinguish between pubertal and pre-pubertal patients, the second of 0.45 UI/L [C.I. 95% 0,20 − 0,70] suggestive of occurred hormonal stimulation in patients with diagnosis of CPP at GnRH test. All 30 patients with CPP in follow-up during suppressive therapy presented uLH values ≤ 0.45 IU/L (pU < 0.05), and uLH collected in prepubertal group control. Conclusions uLH assays on the first morning urine specimen could be considered a low-cost and minimally invasive tool for precocious puberty diagnosing and monitoring, making possible to be easily performed even by a general pediatrician. Thus, this could help referring only selected patients to pediatric endocrinologists. After an appropriate validation, this approach could reasonably reduce hospital attendance and costs of performing more invasive procedures, with a more significant emotional impact on the pediatric patient.