Search

IgA vasculitis (IgAV) is a pediatric disease with skin and systemic manifestations. Here, we conducted genome, transcriptome, and proteome-wide association studies in 2,170 IgAV cases and 5,928 controls, generated IgAV-specific maps of gene expression and splicing from blood of 255 pediatric cases, and reconstructed myeloid-specific regulatory networks to define disease master regulators modulated by the newly identified disease driver genes. We observed significant association at the HLA - DRB1 (OR=1.55, P=1.1×10 -25 ) and fine-mapped specific amino-acid risk substitutions in DRβ1. We discovered two novel non-HLA loci: FCAR (OR=1.51, P=1.0×10 -20 ) encoding a myeloid IgA receptor FcαR, and INPP5D (OR=1.34, P=2.2×10 -09 ) encoding a known inhibitor of FcαR signaling. The FCAR risk locus co-localized with a cis-eQTL increasing FCAR expression; the risk alleles disrupted a PRDM1 binding motif within a myeloid enhancer of FCAR . Another risk locus was associated with a higher genetically predicted levels of plasma IL6R. The IL6R risk haplotype carried a missense variant contributing to accelerated cleavage of IL6R into a soluble form. Using systems biology approaches, we prioritized IgAV master regulators co-modulated by FCAR , INPP5D and IL6R in myeloid cells. We additionally identified 21 shared loci in a cross-phenotype analysis of IgAV with IgA nephropathy, including novel loci PAID4, WLS , and ANKRD55 .

Primary vesicoureteral reflux (VUR) is one of the most common urological abnormalities in infants and children. The association of VUR, urinary tract infection (UTI) and renal parenchymal damage is well established. The most serious complications of VUR-associated reflux nephropathy are hypertension and proteinuria with chronic kidney disease. Over the past two decades, our understanding of the natural history of VUR has improved, which has helped to identify patients at increased risk of both VUR and VUR-associated renal injury. The main goals in the treatment of paediatric patients with VUR are the prevention of recurrent UTIs and minimizing the risk of renal scarring and long-term renal impairment. Currently, there are four options for managing primary VUR in infants and children: surveillance or intermittent treatment of UTIs with management of bladder and bowel dysfunction; continuous antibiotic prophylaxis; endoscopic subureteral injection of tissue-augmenting substances; and ureteral reimplantation via open, laparoscopic or robotic-assisted surgery. Current debates regarding key aspects of management include when to perform diagnostic imaging and how to best identify the paediatric patients that will benefit from continuous antibiotic prophylaxis or surgical intervention, including endoscopic injection therapy and minimally invasive ureteral reimplantation. Evolving technologies, such as artificial intelligence, have the potential to assist clinicians in the decision-making process and in the individualization of diagnostic imaging and treatment of infants and children with VUR in the future., (© 2024. Springer Nature Limited.)

The bidirectional interaction between the gut and the central nervous system (CNS), the so-called gut microbiota-brain axis, is reported to influence brain functions, thus having a potential impact on the development or the progression of several neurodegenerative disorders. Within this context, it has been documented that multiple sclerosis (MS), an autoimmune inflammatory, demyelinating, and neurodegenerative disease of the CNS, is associated with gastrointestinal symptoms, including constipation, dysphagia, and faecal incontinence. Moreover, some evidence suggests the existence of an altered gut microbiota (GM) composition in MS patients with respect to healthy individuals, as well as the potential influence of GM dysbiosis on typical MS features, including increased intestinal permeability, disruption of blood-brain barrier integrity, chronic inflammation, and altered T cells differentiation. Starting from these assumptions, the possible involvement of GM alteration in MS pathogenesis seems likely, and its restoration could represent a supplemental beneficial strategy against this disabling disease. In this regard, the present review will explore possible preventive approaches (including several dietary interventions, the administration of probiotics, prebiotics, synbiotics, and postbiotics, and the use of faecal microbiota transplantation) to be pursued as prophylaxis or in combination with pharmacological treatments with the aim of re-establishing a proper GM, thus helping to prevent the development of this disease or to manage it by alleviating symptoms or slowing down its progression., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Published by Elsevier Ltd.)

This narrative review describes the settlement of the neonatal microbiome during the perinatal period and its importance on human health in the long term. Delivery methods, maternal diet, antibiotic exposure, feeding practices, and early infant contact significantly shape microbial colonization, influencing the infant's immune system, metabolism, and neurodevelopment. By summarizing two decades of research, this review highlights the microbiome's role in disease predisposition and explores interventions like maternal vaginal seeding and probiotic and prebiotic supplementation that may influence microbiome development., Conclusion: The perinatal period is a pivotal phase for the formation and growth of the neonatal microbiome, profoundly impacting long-term health outcomes., What Is Known: • The perinatal period is a critical phase for the development of the neonatal microbiome, with factors such as mode of delivery, maternal diet, antibiotic exposure, and feeding practices influencing its composition and diversity, which has significant implications for long-term health. • The neonatal microbiome plays a vital role in shaping the immune system, metabolism, and neurodevelopment of infants., What Is New: • Recent studies have highlighted the potential of targeted interventions, such as probiotic and prebiotic supplementation, and innovative practices like maternal vaginal seeding, to optimize microbiome development during the perinatal period. • Emerging evidence suggests that specific bacterial genera and species within the neonatal microbiome are associated with reduced risks of developing chronic conditions, indicating new avenues for promoting long-term health starting from early life., (© 2024. The Author(s).)

Background and Objectives: Metabolic syndrome (MetS) is a condition marked by a complex array of physiological, biochemical, and metabolic abnormalities, including central obesity, insulin resistance, high blood pressure, and dyslipidemia (characterized by elevated triglycerides and reduced levels of high-density lipoproteins). The pathogenesis develops from the accumulation of lipid droplets in the hepatocyte (steatosis). This accumulation, in genetically predisposed subjects and with other external stimuli (intestinal dysbiosis, high caloric diet, physical inactivity, stress), activates the production of pro-inflammatory molecules, alter autophagy, and turn on the activity of hepatic stellate cells (HSCs), provoking the low grade chronic inflammation and the fibrosis. This syndrome is associated with a significantly increased risk of developing type 2 diabetes mellitus (T2D), cardiovascular diseases (CVD), vascular, renal, pneumologic, rheumatological, sexual, cutaneous syndromes and overall mortality, with the risk rising five- to seven-fold for T2DM, three-fold for CVD, and one and a half-fold for all-cause mortality. The purpose of this narrative review is to examine metabolic syndrome as a "systemic disease" and its interaction with major internal medicine conditions such as CVD, diabetes, renal failure, and respiratory failure. It is essential for internal medicine practitioners to approach this widespread condition in a "holistic" rather than a fragmented manner, particularly in Western countries. Additionally, it is important to be aware of the non-invasive tools available for assessing this condition. Materials and Methods: We conducted an exhaustive search on PubMed up to July 2024, focusing on terms related to metabolic syndrome and other pathologies (heart, Lung (COPD, asthma, pulmonary hypertension, OSAS) and kidney failure, vascular, rheumatological (osteoarthritis, rheumatoid arthritis), endocrinological, sexual pathologies and neoplastic risks. The review was managed in accordance with the PRISMA statement. Finally, we selected 300 studies (233 papers for the first search strategy and 67 for the second one). Our review included studies that provided insights into metabolic syndrome and non-invasive techniques for evaluating liver fibrosis and steatosis. Studies that were not conducted on humans, were published in languages other than English, or did not assess changes related to heart failure were excluded. Results: The findings revealed a clear correlation between metabolic syndrome and all the pathologies above described, indicating that non-invasive assessments of hepatic fibrosis and steatosis could potentially serve as markers for the severity and progression of the diseases. Conclusions: Metabolic syndrome is a multisystem disorder that impacts organs beyond the liver and disrupts the functioning of various organs. Notably, it is linked to a higher incidence of cardiovascular diseases, independent of traditional cardiovascular risk factors. Non-invasive assessments of hepatic fibrosis and fibrosis allow clinicians to evaluate cardiovascular risk. Additionally, the ability to assess liver steatosis may open new diagnostic, therapeutic, and prognostic avenues for managing metabolic syndrome and its complications, particularly cardiovascular disease, which is the leading cause of death in these patients.

Aims: to measure the clinical impact of contrast-enhanced ultrasound (CEUS) in the diagnosis of -community-acquired pneumonia (CAP), compared to clinical, radiological and ultrasound diagnosis., Methods: 84 patients (47/37 males/females, mean age:78,57±11,7 Y) with clinical suspicion of pneumonia and with ultrasound findings of peripheral lung lesions, were investigated with CEUS for a better characterization. Final diagnosis of 65 cap was obtained with complete disappearance of symptoms and pulmonary nodule(s); 19 neoplasms: 16 patients performed histologically with bronchoscopy; 3 refused (non-invasive diagnosis with basal CT-scan and positron emission tomography (PET) with fluorodeoxyglucose (FDG)). Sensitivity, specificity, overall diagnostic accuracy (ODA) (and corresponding AUROC) of clinical-data (CD), chest X-ray(CXR), Lung-ultrasound(LUS), CEUS were calculated with SPSS 26.0 software., Results: Final diagnosis: 65 CAP, and 19 chest cancers. 9/65 (13%) patients died, of these 7/9 with older age and heart disease as comorbidity. CD: True-Positive (TP):23, True-negative (TN): 17; False-Positive (FP):2; False-negative (FN):42 (sens:35,4% spec:89,5% ODA10%: PPV:92%, NPV:28,8%) (AUROC±SEauc:0,46±0,076); CXR: TP: 36, TN:14; FP:5, FN:29; (sens: 55,4%; spec: 73,7%; ODA: 32%; PPV:87,5%, NPV:32,66%) (AUROC±SEauc:0,645±0,068). US: TP:59; TN: 14; FP:5, FN:6 (sens: 90,8%, spec: 73,7%, ODA: 84,9%, PPV:92,2%, NPV:70%) (AUROC±SEauc:0,9417±0,024); CEUS: TP: 63; TN: 19; FP:0; FN:2 (sens: 96,9%; spec: 100% ODA: 97,5%; PPV: 100%, NPV:90,5%) (AUROC±SEauc:0,98±0,01)., Conclusions: Clinical-data and chest X-RAYS are insufficient to obtain a correct diagnosis of CAP in elderly population; US demonstrated a good accuracy to establish CAP, but with a relatively low specificity; in these cases, CEUS is able to give a correct characterization, allowing you to save the need for a chest contrast-enhanced-CT (CECT).

Aims: We report the results of a real-world study based on heart failure (HF) patients' continuous remote monitoring strategy using the CardioMEMS system to assess the impact of this device on healthcare outcomes, costs, and patients' management and quality of life., Methods and Results: We enrolled seven patients (69.00 ± 4.88 years; 71.43% men) with HF, implanted with CardioMEMS, and daily remote monitored to optimize both tailored adjustments of home therapy and/or hospital infusions of levosimendan. We recorded clinical, pharmacological, biochemical, and echocardiographic parameters and data on hospitalizations, emergency room access, visits, and costs. Following the implantation of CardioMEMS, we observed a 50% reduction in the total number of hospitalizations and a 68.7% reduction in the number of days in the hospital. Accordingly, improved patient quality of life was recorded with EQ-5D (pre 58.57 ± 10.29 vs. 1 year post 84.29 ± 19.02, P = 0.008). Echocardiographic data show a statistically significant improvement in both systolic pulmonary artery pressure (47.86 ± 8.67 vs. 35.14 ± 9.34, P = 0.022) and E/e' (19.33 ± 5.04 vs. 12.58 ± 3.53, P = 0.023). The Quantikine® HS High-Sensitivity Kit determined elevated interleukin-6 values at enrolment in all patients, with a statistically significant reduction after 6 months (P = 0.0211). From an economic point of view, the net savings, including the cost of CardioMEMS, were on average €1580 per patient during the entire period of observation, while the analysis performed 12 months after the implant vs. 12 months before showed a net saving of €860 per patient. The ad hoc analysis performed on the levosimendan infusions resulted in 315 days of hospital avoidance and a saving of €205 158 for the seven patients enrolled during the observation period., Conclusions: This innovative strategy prevents unplanned access to the hospital and contributes to the efficient use of healthcare facilities, human resources, and costs., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The spread of multidrug-resistant Gram-negative bacterial infections is a significant issue for worldwide public health. Gram-negative organisms regularly develop resistance to antibiotics, especially to β-lactam antimicrobials, which can drastically restrict the number of therapies. A third-generation cephalosporin and the non-β-lactam β-lactamase inhibitor avibactam, which exhibits broad-spectrum β-lactamase inhibition in vitro , are combined to form ceftazidime-avibactam (CAZ-AVI). In this narrative review, we summarize data on pharmacokinetic (PK) parameters for CAZ-AVI in both animal and human models of pneumonia, as well as in healthy individuals. We assessed current literature performing an extensive search of the literature, using as search words 'CAZ-AVI', 'pharmacokinetics', 'pneumonia', 'lung', and 'epithelial lining fluid'. Overall, lung exposure studies of CAZ-AVI revealed that the epithelial lining fluid penetration ranges between 30% and 35% of plasma concentration. Despite the fair lung penetration of CAZ-AVI, this antimicrobial agent has a pivotal role in managing patients with multi-drug resistant Gram-negative pneumonia, however further studies are needed to better assess its PK profile.

Robot-assisted extravesical ureteral reimplantation (REVUR) was described for the first time in 2004. Since then, the surgical approach of vesicoureteral reflux (VUR) has changed dramatically. The benefits of this technique are great when compared to the laparoscopic or traditional open approaches. A literature search of PubMed was performed to identify articles covering any aspect of REVUR in the pediatric population. A total of 108 papers published over the period 2004-2024 were collected. Of these, 40 studies were considered valuable in terms of obtaining a complete overview of the REVUR technique. This review aimed to describe the current state of the art of REVUR and define it as the new standard technique for surgical management of selected patients with VUR.

The posthospitalization period following a youth's psychiatric emergency is characterized by marked risk for suicide attempts and rehospitalization. Parental anxiety and uncertainty about parenting strategies may become particularly salient during this period due to fear of youth relapse. These parental factors, then, may negatively impact family functioning, a factor known to mitigate suicide risk. The present study tested a theoretical model to elucidate the relationship between parenting factors and family functioning during this transition period, specifically, whether parental anxiety symptoms and parenting confidence are related and contribute to family functioning longitudinally following youth psychiatric hospitalization. The sample included 147 adolescents and a primary caregiver enrolled in a clinical trial. At baseline (BL) and 6 months (M6), caregivers completed measures of global anxiety symptoms (Brief Symptom Inventory) and parenting confidence (Parenting Relationship Questionnaire). Observer-rated family problem solving and limit setting were assessed (Family Assessment Task) at BL and 12 months (M12). These two measures of family functioning were included in separate path analyses that examined the temporal relations between constructs. After accounting for demographics, BL levels of parenting variables, BL youth functioning, and the presence or absence of youth suicide attempts during follow-up, BL parenting confidence negatively predicted M6 parent anxiety in both models. Additionally, M6 parenting confidence positively predicted M12 problem solving and limit setting. Bidirectional relations between parenting confidence and global anxiety were not supported, nor did global anxiety predict family functioning. Findings suggest that specifically addressing parenting confidence in youth treatment may be beneficial to support family adjustment, particularly following crises. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Introduction: There is growing interest in the use of ChatGPT in the writing and reviewing of scientific articles. In line with the nature of ChatGPT, we tested its effectiveness in the scientific article review process., Methods: We compared the findings of a systematic review of the published literature, produced by researchers in the traditional way, with a version created by ChatGPT, obtained by providing the same inputs as the original paper and a set of instructions (prompts) optimized to obtain the same type of result; we also identified the process that led to a comparable result. In order to assess the effectiveness of ChatGPT in analyzing the systematic review, we selected an existing, replicable study on the experience of health care professionals in the use of digital tools in clinical practice, from which we extracted and downloaded the related 17 publications in Pdf format. Subsequently, we uploaded these references into ChatGPT, setting specific prompts detailing the professional profile required, the context of the application, the expected outputs, and the level of creative freedom (temperature) to a minimum to limit the possibility of "hallucinations". After verifying ChatGPT's understanding of the task, we performed several iterations of the prompt until we obtained a result comparable to the original review. Finally, we systematically compared the results obtained by ChatGPT with those of the reference review., Results: The analysis showed that ChatGPT's results are comparable to human results, although 4 iterations of the prompt are required to approach the human benchmark., Discussion: Although ChatGPT showed comparable capabilities in text review, human authors exhibited greater analytical depth in interpretation. Due to their greater creative freedom, the authors offered more details about the benefits of digital tools in the hospital setting. ChatGPT, however, enriched the analysis by including elements not contemplated initially. The final comparison revealed comparable macro-themes between the two approaches, emphasizing the need for careful human validation to ensure the full integrity and depth of the analysis., Conclusions: Generative artificial intelligence (AI), represented by ChatGPT, showed significant potential in revolutionizing the production of scientific literature by supporting healthcare professionals. Although there are challenges that require careful evaluation, ChatGPT's results are comparable to human results. The key element is not so much the superiority of AI over humans but the human ability to configure and direct AI for optimal or even potentially superior human results.

Background: Simulation-based training plays a significant role in surgical education, especially in minimally invasive pediatric surgery and urology. This study aimed to evaluate a novel 3D-printed model as training tool for endoscopic injection of bulking agent., Methods: Forty-three attendees and ten teaching faculty members were invited to complete a post hoc questionnaire after completing training sessions using the Fish Tank Simulation Model (FTSM). The survey consisted of a 7-question 5-point Likert scale to assess the model's realism (face validity) and its effectiveness as training tool (content validity)., Results: Regarding the training status, 20/53 (37.7%) participants were fellow and/or specialist in pediatric surgery and 33/53 (62.3%) were surgeons in training. Their level of confidence in endoscopic injection procedure was defined as novice (< 10 procedures per year) in 33/53 (62.3%), intermediate (10-20 procedures per year) in 10/53 (18.9%), and expert (> 20 procedures per year) in 10/53 (18.9%). Regarding both face validity and content validity assessments, no statistically significant differences were found between scores given by novice vs intermediate/expert groups. Similarly, no statistically significant differences emerged between scores given by participant vs faculty groups assessing the content validity of the FTSM. The FTSM was considered a good teaching tool for beginners by 44/53 (83%) and for pediatric surgeons/urologists by 38/53 (71.7%)., Conclusions: The 3D-printed Fish Tank Simulation Model proved to be a valuable, high-fidelity, easily accessible, cost-effective, hygienic, and domestic-use training tool for pediatric surgeons/urologists conducting the procedure. The model's user-friendly design and realistic environment enhanced learning opportunities for trainees, regardless of their experience level or training status. Nevertheless, further development is necessary, particularly in enhancing the realism of the ureteral hiatus and reproducing more complex anatomy, to make it beneficial for the training of advanced surgeons., (© 2024. The Author(s).)

Protein import and genome replication are essential processes for mitochondrial biogenesis and propagation. The J-domain proteins Pam16 and Pam18 regulate the presequence translocase of the mitochondrial inner membrane. In the protozoan Trypanosoma brucei, their counterparts are TbPam16 and TbPam18, which are essential for the procyclic form (PCF) of the parasite, though not involved in mitochondrial protein import. Here, we show that during evolution, the 2 proteins have been repurposed to regulate the replication of maxicircles within the intricate kDNA network, the most complex mitochondrial genome known. TbPam18 and TbPam16 have inactive J-domains suggesting a function independent of heat shock proteins. However, their single transmembrane domain is essential for function. Pulldown of TbPam16 identifies a putative client protein, termed MaRF11, the depletion of which causes the selective loss of maxicircles, akin to the effects observed for TbPam18 and TbPam16. Moreover, depletion of the mitochondrial proteasome results in increased levels of MaRF11. Thus, we have discovered a protein complex comprising TbPam18, TbPam16, and MaRF11, that controls maxicircle replication. We propose a working model in which the matrix protein MaRF11 functions downstream of the 2 integral inner membrane proteins TbPam18 and TbPam16. Moreover, we suggest that the levels of MaRF11 are controlled by the mitochondrial proteasome., Competing Interests: AS is a member of the PLOS Biology Editorial Board., (Copyright: © 2024 von Känel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A 16-year-old girl with down syndrome came to our attention for recurrent postprandial vomiting and significant weight loss (>5 kgs). Diagnostic assessment (barium swallow study, ultrasonography, and CT) confirmed hypertrophic pyloric stenosis (HPS). Initial attempt with endoscopic dilation was not successful. The patient underwent Heineke-Mikulicz pyloroplasty. Full oral feeding was achieved by Day 7 postoperatively. At 6-month follow-up, the patient reported relief of symptoms, normal feeding habits and substantial weight gain. HPS should be considered in the differential diagnosis of recurrent vomiting, regardless of age. A comprehensive diagnostic work-up, including ultrasonography, endoscopy, and CT, is recommended to confirm the diagnosis., (© 2024 Wiley Periodicals LLC.)

The development of pressure ulcers, associated with increased temperature and moisture in specific areas of the body, and the risk of microbial infections in patients lying in a static position for prolonged periods of time represents a serious issue in medicine. In order to prevent the formation of pressure ulcers, this work aims to present advanced nanostructured coatings developed by three research groups. Nanometric silver, ash and functionalized torrefied biomass were the basis for the treatment of wound dressings to improve thermal conductivity and antimicrobial properties of the conventional cotton gauzes. Each treatment was performed according to its own optimized method. The treated fabrics were characterized in terms of antimicrobial properties, heat transfer, morphology and hydrophobic behavior. The results demonstrated the effectiveness of the deposition treatments also in synergistic actions. In particular, the antibacterial efficacy was improved in all the samples by the addition of silver treatment, and the thermal conductivity was enhanced by around 58% with nanometric ashes. A further step of the study involved the designing of two multilayer systems evaluated using circuit models for determining the total thermal conductivity. In this way, both systems were designed with the aim to guarantee simultaneous efficacy: high antibacterial and hydrophilic properties at the skin level and more hydrophobic and conductive behaviors toward the external environment.

Partial hospital programs (PHPs) are a vital mental health service for youth at risk for suicide. Yet, few studies have examined trajectories of suicidal ideation and depressive symptoms, two important risk factors for suicidal behavior, over the course of care. Moreover, little is known about factors that may impact these trajectories among youth in PHPs. The present study examined trajectories of suicidal ideation and depressive symptoms, as well as clinical and demographic predictors of these changes, among youth enrolled in two PHPs. A sample of 253 youth ( M = 15.3; SD = 1.4; range = 12-18; 68.8% female; 63.2% White; 75.1% non-Hispanic/Latino/a/x) completed repeated measures of suicidal ideation severity and depressive symptoms during treatment. Trajectories of these outcomes were examined using two separate latent growth models. Recent history of self-injurious behaviors and demographics were tested as predictors of trajectories using a taxonomic approach. Overall, suicidal ideation and depressive symptoms declined over the course of care. Sex, history of self-injury, and sexual identity were associated with variability in one or both trajectories of change. Results suggest individual variability in the rate of change among youth in PHPs. Such information may be used to aid in treatment planning and quality improvement efforts within PHPs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).age = 15.3; SD = 1.4; range = 12-18; 68.8% female; 63.2% White; 75.1% non-Hispanic/Latino/a/x) completed repeated measures of suicidal ideation severity and depressive symptoms during treatment. Trajectories of these outcomes were examined using two separate latent growth models. Recent history of self-injurious behaviors and demographics were tested as predictors of trajectories using a taxonomic approach. Overall, suicidal ideation and depressive symptoms declined over the course of care. Sex, history of self-injury, and sexual identity were associated with variability in one or both trajectories of change. Results suggest individual variability in the rate of change among youth in PHPs. Such information may be used to aid in treatment planning and quality improvement efforts within PHPs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background and Aims: Indocyanine Green Fluorescence (ICG-F)- guided surgery is becoming an increasingly helpful tool in pediatric surgical care. This consensus statement investigates the utility of ICG-F in various pediatric surgical applications, primarily focusing on its evidence base, safety, indications, use across different surgical specialties and dosing strategies. The aim is to establish an international consensus for ICG-F use in pediatric surgery., Methods: An international panel of 15 pediatric surgeons from 9 countries was assembled. The structured process consisted of a rapid scoping review, iterative discussion sessions, mixed-methods studies with key stakeholders, and voting rounds on individual statements to create draft consensus statements., Results: 100 articles were identified during the review and summarized by application. Based on this condensed evidence, consensus statements were generated after 3 iterative rounds of anonymous voting. Key areas of agreement were quality of evidence, the safety of ICG, pediatric surgical indications, utilization per surgical specialty, and dosing of ICG., Conclusion: This consensus statement aims to guide healthcare professionals in managing ICG-F use in pediatric surgical cases based on the best available evidence, key stakeholder consultation, and expert opinions. Despite ICG-F's promising potential, the need for higher-quality evidence, prospective trials, and safety studies is underscored. The consensus also provides a framework for pediatric surgeons to utilize ICG-F effectively., Level of Evidence: III., Competing Interests: Conflict of interest All authors have no disclosures or conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Deep learning (DL) has shown potential to provide powerful representations of bulk RNA-seq data in cancer research. However, there is no consensus regarding the impact of design choices of DL approaches on the performance of the learned representation, including the model architecture, the training methodology and the various hyperparameters. To address this problem, we evaluate the performance of various design choices of DL representation learning methods using TCGA and DepMap pan-cancer datasets and assess their predictive power for survival and gene essentiality predictions. We demonstrate that baseline methods achieve comparable or superior performance compared to more complex models on survival predictions tasks. DL representation methods, however, are the most efficient to predict the gene essentiality of cell lines. We show that auto-encoders (AE) are consistently improved by techniques such as masking and multi-head training. Our results suggest that the impact of DL representations and of pretraining are highly task- and architecture-dependent, highlighting the need for adopting rigorous evaluation guidelines. These guidelines for robust evaluation are implemented in a pipeline made available to the research community., (© 2024. The Author(s).)

Introduction: The COVID-19 pandemic significantly impacted the emotional well-being of adolescents worldwide. Some studies suggested that individuals with high Environmental Sensitivity may have been more likely to experience poor psychological adjustment during the pandemic than those with lower sensitivity. However, there is still limited research on how emotional responses varied across different stages of the pandemic and whether Environmental Sensitivity increased adolescents' vulnerability to the psychological impact of prolonged pandemic restrictions., Methods: To address this gap, this study used a three-year longitudinal design (2020-2022) with a sample of 453 adolescents. They completed an online survey measuring their positive and negative emotions throughout the pandemic period, with Environmental Sensitivity considered a time-invariant covariate., Results: The results revealed that all participants, regardless of their level of Environmental Sensitivity, experienced a decrease in positive emotionality between the first and second years. However, this trend reversed, showing an increase between the second and third years. Regarding negative emotions, highly sensitive adolescents experienced a significant linear increase over time. In contrast, low-and medium-sensitive adolescents exhibited a quadratic trend, with a notable increase in negative emotions between the first and second years, followed by a slight decrease between the second and third years., Discussion: These findings provide further evidence of the negative impact of the pandemic on adolescents' emotional well-being. They also support the notion that Environmental Sensitivity is associated with individuals' ability to respond and adjust to adverse life events, with significant implications for future research and practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Dragone, Colella, Esposito and Bacchini.)

Introduction: Classical neutral mechanical alignment in total knee arthroplasty (TKA) has been a standard paradigm, while more recently, other alignment schemas, such as kinematic, individualized, and functional, have been explored. This study aimed to investigate the effect of three-dimensional (3D) computed tomography (CT)-based surgical robotics inputs on a classically trained surgeon's TKA component positions and alignment targets over time., Materials and Methods: Data from 1,394 consecutive robotically-assisted TKAs by a single surgeon from 2016 to 2020 were analyzed. Metrics collected included pre-balance planned implant component positions, final planned implant component positions after soft tissue balancing, and constitutional alignment from CT scans. Joint line obliquity was plotted against the arithmetic hip-knee angle (aHKA) using coronal plane alignment of the knee (CPAK). Three categories of alignment strategy were defined: true mechanical alignment (tMA), adjusted mechanical alignment (aMA), and no mechanical alignment (noMA)., Results: A shift to overall varus component positioning was observed over the years. Joint line obliquity according to CPAK showed a wider spread in later years, and the distribution of tibial and femoral coronal alignment angles expanded over time., Conclusion: The study revealed a change in alignment targets and final positioning of components away from neutral biomechanical axes in a large volume of TKAs by a single, classically trained surgeon over five years of using a robotic arm-assisted TKA system with CT-based planning. The most dominant factor for this change was the use of 3D CT planning, allowing the surgeon to assess patient-specific anatomy and plan accordingly. Outcome data is needed to determine if this change in behavior and surgical technique was beneficial. In summary, using a CT scan-based robotically assisted technique led to a gradual and complete shift from tMA to predominantly a non-mechanically aligned philosophy in TKA.

Introduction: The dominance behavioral system, a fundamental aspect of human behavior, orchestrates the drive for dominance, regulates dominant-subordinate dynamics, and shapes responses to perceived power dynamics. While the existing literature extensively delves into the components of this system, scant attention is paid to its interplay with mentalization, theory of mind, and assertiveness. Moreover, gender disparities in dominance behaviors are largely studied in terms of biological variables (levels of testosterone) and clinical populations. This study aims to understand the relationships between activation strategies of the dominance behavioral system, mentalization processes, theory of mind abilities, and levels of social discomfort in assertive communication. Moreover, to identify gender differences in the dominance behavioral system in a non-clinical sample., Methods: Our sample was composed of 67 students from a non-clinical population. They claimed the absence of any psychological, neurological, or developmental disorders., Results: A regression analysis was performed, and we found that levels of mentalization predict levels of hyperactivation of dominance behavioral system, but no significant results for the deactivation levels of the system were found. Moreover, no gender differences were found in levels of activations of the dominance behavioral system., Conclusion: These findings underscore the pivotal role of mentalization abilities in interpersonal dynamics, emphasizing the need for individuals to navigate social interactions adeptly. Furthermore, our research unveils implications for individual well-being and psychopathology, urging further investigation into how these dimensions intersect with various psychological disorders. By discerning the intricate mechanisms at play, we can develop targeted therapeutic interventions tailored to specific behavioral patterns, ultimately enhancing psychological resilience and fostering healthier social relationships in a non-clinical population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cerciello, Esposito, La Penna, Sica and Frolli.)

School bullying represents a widespread expression of violence in the peer context. Guided by the social-ecological model, this study investigated the longitudinal and transactional pathways linking domestic and neighborhood/community violence exposure (through direct victimization and witnessing), self-serving cognitive distortions (CDs), and school bullying perpetration. Furthermore, consistent with the previous literature, we tested the cognitive desensitization process that could develop in response to chronically violent contexts. Two four-wave cross-lagged panel mediation models were tested in a sample of 778 high school students (28.1% males; M age [Time 1; T1] = 14.20, SD = 0.58). The results showed differential effects of multiple contexts and forms of violence exposure, with domestic violence victimization and community violence witnessing being associated with self-serving CDs and bullying perpetration over time. Moreover, significant associations between CDs and bullying perpetration over time were found, with bidirectional effects for each of these longitudinal patterns. Finally, self-serving CDs significantly mediated the relationships between both domestic violence victimization and community violence witnessing and school bullying perpetration. These findings highlight the need to consider school bullying as a social phenomenon stemming from a complex and bidirectional interplay between individuals and the environments they inhabit, confirming a basic postulate that "violence breeds violence".

Background: Little is known about the burden of illness experienced by people with cystic fibrosis (pwCF) since the advent of CF transmembrane conductance regulator (CFTR) modulator therapies. Studies that characterize the nature of illness burden are needed to inform the development and implementation of palliative care programs that can serve this population and address quality of life concerns., Methods: Adults with CF treated at five U.S. CF centers were surveyed to obtain baseline data for the Improving Life with CF primary palliative care implementation trial. Consenting patients completed the Integrated Palliative Care Outcome Scale (IPOS), a multidimensional measure of unmet needs for palliative care. Sociodemographic and clinical information was also obtained. The associations among these variables were examined through bivariate and multivariable analyses., Results: Among 256 adults, the most distressing symptoms included not feeling "at peace", communication difficulties with family/friends, anxiety over illness or its treatment, and a lack of energy. In the multivariable analyses, CFTR modulator use was associated with lower IPOS total and physical symptoms scores; female sex and increased hospitalizations were associated with higher scores. Increased age and history of distal intestinal obstructive syndrome were associated with higher IPOS physical symptoms scores., Conclusions: These findings illuminate the nature of illness burden for pwCF in the era of CFTR modulator therapies. Although illness burden is positively affected by modulator therapy, there is a continuing need for palliative care to address physical, emotional, and spiritual distress, and the communication and practical needs experienced by adults with CF., Competing Interests: Declaration of Competing Interest AMG reports personal fees from the Belgian Cystic Fibrosis Foundation/King Baudouin Foundation; grants, personal fees, and travel reimbursement from the Cystic Fibrosis Foundation; grants from the Dutch Cystic Fibrosis Foundation; travel reimbursement from the European Cystic Fibrosis Society; travel reimbursement from the French Cystic Fibrosis Society; personal fees from the Italian Cystic Fibrosis Research Foundation; grants from the National Heart, Lung, and Blood Institute; personal fees from the Saudi Pediatric Pulmonology Association; grants and personal fees from Vertex Pharmaceuticals; and personal fees from Virginia Commonwealth University. RP reports royalties from Oxford University Press and UpToDate, honorarium from the 2023 Sapporo Conference on Palliative and Supportive Care, and travel reimbursement from the 2023 Sapporo Conference on Palliative and Supportive Care. JW reports support from Cystic Fibrosis Foundation Data Safety Monitoring Board and a Cystic Fibrosis Foundation Center grant. DF reports grant funding and travel reimbursement from the Cystic Fibrosis Foundation outside the submitted work. ES reports research funding from the National Institutes of Health (NIH, National Center for Complementary and Integrative Health, National Institute of Neurological Disorders and Stroke), Veterans Health Administration (Headache Centers of Excellence), and the American Heart Association, as well as fees for consulting from GlaxoSmithKline, Theranica, Abbvie, and Click Therapeutics. RWL reports grants to institution, consultant fees, advisory board participation, and travel reimbursement from Vertex Pharmaceuticals and grants to the institution from the Cystic Fibrosis Foundation. PW reports grant funding and travel reimbursement from the Cystic Fibrosis Foundation. BMO reports grant funding and fees as a consultant from the Cystic Fibrosis Foundation and fees as a consultant from Vertex Pharmaceuticals. LD reports royalties from UpToDate and research funding from NIH (National Institute of Nursing Research). No other authors have declarations of interest., (Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

This study intricately unfolds a pioneering methodology for remediating contaminants in a persistent light non-aqueous phase liquids (LNAPL)-contaminated site. The remediation strategy seamlessly integrates enhanced desorption and in-situ chemical oxidation (ISCO), orchestrating the injection of PetroCleanze® (a desorbent) and RegenOx® (an oxidizer) through meticulously designed wells. These injections, based on detailed geological and hydrogeological assessments, aim at mobilizing residual contaminants for subsequent extraction. Real-time subsurface dynamics are investigated through geophysical monitoring, employing electrical resistivity tomography (ERT) to trace reagent migration pathways via their effect on bulk electrical conductivity. The integration of groundwater sampling data aims at providing additional insights into the transformations of contaminants in the spatiotemporal context. Vivid two-dimensional time-lapse ERT sections showcase the evolution of resistivity anomalies, providing high-resolution evidence of the heterogeneity, dispersion pathways of desorbent and oxidant, and residual LNAPL mobilization. Hydrochemical analyses complement this, revealing effective mobilization processes with increasing aqueous concentrations of total petroleum hydrocarbons (TPH) over time. Speciation analysis unveils the intricate interplay of desorption and oxidation, portraying the dynamic fractionation of hydrocarbon components. The hydrogeophysical and data-driven framework not only delivers qualitative and quantitative insights into reagent and contaminant distribution but also enhances understanding of spatial and temporal physio-chemical changes during the remediation process. Time-lapse ERT visually narrates the reagent's journey through time, while chemical analyses depict the unfolding processes of desorption and oxidation across space and time. The coupling of hydrogeophysical and chemical findings pictures the transformations of pollutants following the sequence of product injection and the push and pull activities, capturing the removal of mobilized contaminants through hydraulic barrier wells. This enhanced understanding proves instrumental towards optimizing and tailoring remediation efforts, especially in heterogeneous environmental settings. This study establishes a new standard for a sophisticated and innovative contaminant remediation approach, advancing environmental practices through the harmonized analysis of geophysical and chemical data., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background : To investigate anatomical and functional changes of the macula caused by epiretinal membrane (ERM) peeling procedures in patients with or without posterior vitreous detachment (PVD). Methods : This is a multicentric prospective observational study on thirty-seven (37) patients affected by symptomatic ERM who underwent 25-gauge pars plana vitrectomy (PPV), induction of a PVD (as needed) and peeling of both the internal limiting membrane (ILM) and ERM. Optical coherence tomography-angiography (OCT-A) ( RS 3000 , Nidek, Japan) and microperimetry ( MP-3 , Nidek, Japan) were performed; central retinal thickness (CRT), foveal avascular zone (FAZ) area and perimeter, vessel density and perfusion density, retinal sensitivity and fixation stability (as a total mean retinal sensitivity (MRS), and MRS in the ellipse area and bivariate contour ellipse area (BCEA)) were recorded at baseline and up to postoperative month 3. Results : Eyes were classified as having complete PVD (51.4%) or incomplete PVD (48.6%). At baseline, patients with incomplete PVD had worse best-corrected distance visual acuity (BCDVA), total MRS, MRS in the ellipse area and BCEA, and higher CRT than patients with complete PVD. At month 3, the differences in BCDVA between the two groups remained statistically significant, with patients with incomplete PVD having worse results (difference: 0.199 logMAR, p < 0.001). The difference in the MRS in the ellipse area was statistically significant at month 3 (-3.378 Db, p = 0.035), with greater improvement in patients with complete PVD. Conclusions : Our study shows that patients with incomplete PVD have worse conditions at baseline than patients with complete PVD, and the differences in visual acuity and retinal sensitivity were maintained postoperatively.

The COVID-19 pandemic drastically affected many areas and contexts of today's society, including school and family. Several studies focused on the worldwide effects of school closures on students' learning outcomes, context, and well-being. However, the data emerging from these studies are often inconsistent and fragmentary, highlighting the need of a comprehensive analysis of the phenomenon. This need is especially urgent for the countries with the most severe school closure, like Italy. This systematic review aims to collect the opinions of parents, teachers, and students on: other dimensions of Italian primary school students affected by school closures, beyond academic performance; hypothetical agreement between the opinions of parents, teachers, and students regarding the different effects of school closures on Italian primary school students; possible differences between the effects of school closures on Italian primary school students and the students in other countries. Our search was conducted using PRISMA 2020 guidelines on Web of Science, Pubmed, Scopus, and EBSCOHost. The results obtained from 34 articles revealed a strong concern on the part of all stakeholders involved in learning during the pandemic, with evident negative effects for Italian school students. The constraint on distance learning led to a drastic change in everyone's routine, and a negative emotional change on the part of young students. Parents and teachers generally considered distance learning to be ineffective for the education of their children and students; they encountered technical-practical difficulties in the use of electronic devices for participation in school activities; overall learning deficits on the part of students, especially in mathematics, as confirmed by INVALSI results were also found. The investigation reveals a condition of shared emotional and academic performance difficulty, and a further challenging circumstance for students previously at risk of marginalization. Further research in this field is paramount to identify new and adequate recovery strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Trotta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Posidonia oceanica (L.) Delile 1813 banquette provides precious ecosystem services for Mediterranean beach nourishment and protection, representing an important way of energy transfer through marine-coastal habitats. It is surprising to note how it is poorly investigated, especially concerning its double role as potential sink and source of chemicals. In particular, few studies exist about the metal (loid)s occurrence and no data are available on emerging contaminants, such as Rare Earth Elements (REEs). The present research investigated for the first time the concentrations of twenty-eight metal(loid)s and fifteen REEs in a well-structured banquette along the Italian coast (Central Tyrrhenian Sea) showing that (i) metal(loid)s and REEs occur in banquettes, with higher relative concentrations of some metal(loid)s (B, Sr, Mn, Fe, Al, Zn) and REEs (Ce, Y, La, Nd) with no statistically significant seasonal variations; (ii) Posidonia banquettes may represent an interesting biological model for chemicals monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)