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Current federal aid allocation policies do an admirable job of targeting aid to school districts serving the neediest students. But these policies have one significant, underlying weakness: they fail to consider states' effort levels (and their capacities to raise revenue). In this article, the authors propose a new federal aid framework that functions similarly to how state finance systems are supposed to work--that is, by distributing federal aid based on both costs/needs as well as states' and districts' ability and willingness to pay their fair shares of bringing all districts up to a minimum adequate level. As a proof of concept, in their report the authors provide extensive calculations and analysis to simulate one reasonable manifestation of that framework: a voluntary supplemental federal aid program in which eligibility is contingent upon fair share state and local contributions (i.e., minimum effort), and new federal funds fill the gaps between that contribution and adequate funding levels in eligible states. While readers are encouraged to read the full report, a summary of this simulation is offered here showing that what's needed to ensure adequate funding for all districts is reasonable and doable.

This literature review rigorously examines the growing scientific interest in computational methods for Tissue Engineering and Regenerative Medicine biofabrication, a leading-edge area in biomedical innovation, emphasizing the need for accurate, multi-stage, and multi-component biofabrication process models. The paper presents a comprehensive bibliometric and contextual analysis, followed by a literature review, to shed light on the vast potential of computational methods in this domain. It reveals that most existing methods focus on single biofabrication process stages and components, and there is a significant gap in approaches that utilize accurate models encompassing both biological and technological aspects. This analysis underscores the indispensable role of these methods in understanding and effectively manipulating complex biological systems and the necessity for developing computational methods that span multiple stages and components. The review concludes that such comprehensive computational methods are essential for developing innovative and efficient Tissue Engineering and Regenerative Medicine biofabrication solutions, driving forward advancements in this dynamic and evolving field.

Cavitation in water only, no matter whether hydrodynamic or acoustic, is a zero-waste circular economy process to convert industrial citrus processing waste into high-performance polysaccharides in high demand in a single-step at room temperature and ambient pressure using a modest amount of electricity as the only energy input. Following previous reports in which we used hydrodynamic cavitation, we now use an industrial acoustic sonicator to demonstrate the general viability of cavitation to convert biowaste residue of the industrial squeezing of pigmented sweet orange (Citrus sinensis) into highly bioactive “IntegroPectin” pectin and micronized cellulose “CytroCell”. From biomedicine through advanced composite membranes, said biomaterials hold great applicative potential. We conclude discussing the economic and technical feasibility of industrial implementation of the “CytroCav” process.

The economic burden of chronic diseases such as cancer could negatively impact patients’ health and quality of life. The daily management of the disease results in economic needs that patients often face directly, which may lead to real toxicity, just defined as financial toxicity. This study aims to explore cancer patients’ experiences, emotions, opinions, and feelings related to the phenomenon of financial toxicity. A phenomenological qualitative descriptive study was conducted through face-to-face interviews with adult oncological patients. The sample (n = 20) was predominantly composed of females (with a meanly 58 years old) with breast cancer and in chemotherapy treatment. The most relevant topics that emerged from the patients’ experiences were the impact on work, the distance from the treatment centre, the economic efforts, the impact on the quality of life, and the healthcare workers’ support during the healthcare pathway. From the phenomenological analysis of the interviews, three main themes and seven related subthemes emerged. This study provided a phenomenological interpretation of financial toxicity in adult cancer patients and underlines that this issue involves families or caregivers, too. Financial problems appear relevant for those who experience cancer and should be included in a routine assessment by healthcare professionals.

Abstract Background Rib fractures are one of the most common traumatic injuries and may result in significant morbidity and mortality. Despite growing evidence, technological advances and increasing acceptance, surgical stabilization of rib fractures (SSRF) remains not uniformly considered in trauma centers. Indications, contraindications, appropriate timing, surgical approaches and utilized implants are part of an ongoing debate. The present position paper, which is endorsed by the World Society of Emergency Surgery (WSES), and supported by the Chest Wall Injury Society, aims to provide a review of the literature investigating the use of SSRF in rib fracture management to develop graded position statements, providing an updated guide and reference for SSRF. Methods This position paper was developed according to the WSES methodology. A steering committee performed the literature review and drafted the position paper. An international panel of experts then critically revised the manuscript and discussed it in detail, to develop a consensus on the position statements. Results A total of 287 studies (systematic reviews, randomized clinical trial, prospective and retrospective comparative studies, case series, original articles) have been selected from an initial pool of 9928 studies. Thirty-nine graded position statements were put forward to address eight crucial aspects of SSRF: surgical indications, contraindications, optimal timing of surgery, preoperative imaging evaluation, rib fracture sites for surgical fixation, management of concurrent thoracic injuries, surgical approach, stabilization methods and material selection. Conclusion This consensus document addresses the key focus questions on surgical treatment of rib fractures. The expert recommendations clarify current evidences on SSRF indications, timing, operative planning, approaches and techniques, with the aim to guide clinicians in optimizing the management of rib fractures, to improve patient outcomes and direct future research.

Abstract Here we present the growth of molecular beam epitaxy (MBE) CsPbBr3 perovskite films in the orthorhombic crystal structure, with unique structural and morphological properties. CsPbBr3 MBE perovskite films, with thickness ranging from a few nm to 300 nm, were grown in ultra-high vacuum on a Si(111)7 × 7 reconstructed surface, and after the formation of about 2 nm of SiO2, obtained exposing the clean reconstructed Si surface to molecular oxygen that serves to decouple the film from substrate. X-ray diffraction, and electron microscopies, such as scanning electron microscopy and high-angle annular dark-field scanning transmission electron microscopy measurements showed remarkable structural, as well as morphological features, indicating extremely high crystallinity over a large area and across the bulk of the perovskite film. Through the X-ray diffraction patterns we found very narrow (002) and (110) reflections of CsPbBr3 in pure orthorhombic phase, exhibiting a full width at half maximum of only 0.035°, value similar to a bulk Si single crystals, and a surface morphology composed of flat areas up to micrometres in lateral size. Our results shed new light both on preparation of high crystal quality perovskite films, and on the intrinsic properties of this striking fully-inorganic materials, which are exploitable for potential applications in electronic/optoelectronic devices and next generation photovoltaic solar cells.

The conversion of solar energy into electricity via the photovoltaic (PV) effect has been rapidly developing in the last decades due to its potential for transition from fossil fuels to renewable energy based economies. In particular, the advances in PV technology and on the economy of scale permitted to reduce the cost of the energy produced with solar cells down to the energy cost of conventional fossil fuel. Thus, PV will play an important role to address the biggest challenges of our planet including global warming, climate change and air pollution. In this paper, we will introduce the photovoltaic technology recalling the working principle of the photovoltaic conversion and describing the different PV available on the market and under development. In the last section, we will focus more on the emerging technology of the halide perovskite, which is the research subject of the authors.

Solid Oxide Fuel Cells (SOFCs) have shown unique performance in terms of greater electrical efficiency and thermochemical integrity with the power systems compared to gas turbines and internal combustion engines. Nonetheless, simple and reliable models still must be defined. In this paper, a comparisonbetween a grey-box model and a 1-D model of a SOFC is performed to understand the impact of the heat transfer inside the cell on the internal temperature distribution of the solid electrolyte. Hence, a significant internal temperature peak of the solid electrolyte is observed for a known difference between anode and cathode inlet temperatures. Indeed, it highlights the difference between the 1-D model andthe grey-box model regarding the thermal conditioning of the SOFC. Therefore, the results of this study can be used to investigate the reliability of the thermal results of box models in system-level simulations.

Abstract Introduction Despite an improved understanding of its pathogenesis, dry eye disease (DED) remains relatively underestimated and its treatment challenging. A better alignment between the clinical evaluation and the patient self-assessment also requires capturing the whole patient experience of DED. This project aimed to unveil this experience through narrative medicine (NM). Methods The project involved 38 expert centres in Italy and one in San Marino, targeting adult patients with DED, their informal caregivers and their treating ophthalmologists. Written narratives and sociodemographic and quality of life (QoL)-related data were anonymously collected through the project’s webpage. Narratives were analysed through MAXQDA (VERBI Software, Berlin, Germany), NM classifications and content analysis. Results A total of 171 patients with DED, 37 informal caregivers and 81 ophthalmologists participated in the research. DED was defined as a disabling condition by 19% of patients and 35% of caregivers; 70% of patients reported that a therapeutic alliance is an integral part of DED treatment and 32% hope for more effective therapies. Forty-four per cent of patients assessed their own QoL as good; however, DED emerged as importantly impacting work performance and social events. DED physical, emotional and economic burden and the cruciality of a trusting care relationship represent the main themes that emerged across all narratives, while empathy and effective treatment are among the factors favouring coping with DED. Conclusion This project marked a pioneering initiative investigating the lived experience of patients with DED through NM, simultaneously involving all viewpoints involved in the care pathway. NM enabled the unveiling of factors favouring the ability to cope with DED and its associated QoL implications and provided valuable insights to improve the therapeutic alliance.

Abstract The development of selective and nontoxic immunotherapy targeting prostate cancer (PC) is challenging. Interleukin (IL)30 plays immunoinhibitory and oncogenic roles in PC, and its tumor-specific suppression may have significant clinical implications. CRISPR/Cas9-mediated IL30 gene deletion in PC xenografts using anti-PSCA antibody-driven lipid nanocomplexes (Cas9gRNA-hIL30-PSCA NxPs) revealed significant genome editing efficiency and circulation stability without off-target effects or organ toxicity. Biweekly intravenous administration of Cas9gRNA-hIL30-PSCA NxPs to PC-bearing mice inhibited tumor growth and metastasis and improved survival. Mechanistically, Cas9gRNA-hIL30-PSCA NxPs suppressed ANGPTL 1/2/4, IL1β, CCL2, CXCL1/6, SERPINE1-F1, EFNB2, PLG, PF4, VEGFA, VEGFD, ANG, TGFβ1, EGF and HGF expression in human PC cells while upregulated CDH1, DKK3 and PTEN expression, leading to low proliferation and extensive ischemic necrosis. In the syngeneic PC model, IL30-targeting immunoliposomes downregulated NFKB1 expression and prevented intratumoral influx of CD11b+Gr-1+MDCs, Foxp3+Tregs, and NKp46+RORγt+ILC3, and prolonged host survival by inhibiting tumor progression. This study serves as a proof of principle that immunoliposome-based targeted delivery of Cas9gRNA-IL30 represent a potentially safe and effective strategy for PC treatment.

Abstract Perovskite solar cells have rapidly advanced, achieving over 26% power conversion efficiency on the laboratory scale. However, transitioning to large-scale production remains a challenge due to limitations in conventional fabrication methods like spin coating. Here, we introduce an optimized blade coating process for the scalable fabrication of large-area (15 cm × 15 cm) perovskite solar modules with a nickel oxide hole transport layer, performed in ambient air and utilizing a non-toxic solvent system. Self-assembled monolayers between the nickel oxide and perovskite layer improve the uniformity and morphology of the perovskite film. Perovskite solar modules with a 110 cm2 active area achieve a power conversion efficiency of 12.6%. Moreover, encapsulated modules retained 84% of their initial efficiency after 1,000 hours at 85 °C in air (ISOS-T-1). This study demonstrates progress in the large-scale production of perovskite solar cells that combine efficiency with long-term stability.

Abstract Prostate cancer (PC) is an age-related disease and represents, after lung cancer, the second cause of cancer death in males worldwide. Mortality is due to the metastatic disease, which mainly involves the bones, lungs, and liver. In the last 20 years, the incidence of metastatic PC has increased in Western Countries, and a further increase is expected in the near future, due to the population ageing. Current treatment options, including state of the art cancer immunotherapy, need to be more effective to achieve long-term disease control. The most significant anatomical barrier to overcome to improve the effectiveness of current and newly designed drug strategies consists of the prostatic stroma, in particular the fibroblasts and the extracellular matrix, which are the most abundant components of both the normal and tumor prostatic microenvironment. By weaving a complex communication network with the glandular epithelium, the immune cells, the microbiota, the endothelium, and the nerves, in the healthy prostatic microenvironment, the fibroblasts and the extracellular matrix support organ development and homeostasis. However, during inflammation, ageing and prostate tumorigenesis, they undergo dramatic phenotypic and genotypic changes, which impact on tumor growth and progression and on the development of therapy resistance. Here, we focus on the characteristics and functions of the prostate associated fibroblasts and of the extracellular matrix in health and cancer. We emphasize their roles in shaping tumor behavior and the feasibility of manipulating and/or targeting these stromal components to overcome the limitations of current treatments and to improve precision medicine’s chances of success.

Abstract Point-of-care serological and direct antigen testing offers actionable insights for diagnosing challenging illnesses, empowering distributed health systems. Here, we report a POC-compatible serologic test for Lyme disease (LD), leveraging synthetic peptides specific to LD antibodies and a paper-based platform for rapid, and cost-effective diagnosis. Antigenic epitopes conserved across Borrelia burgdorferi genospecies, targeted by IgG and IgM antibodies, are selected to develop a multiplexed panel for detection of LD antibodies from patient sera. Multiple peptide epitopes, when combined synergistically with a machine learning-based diagnostic model achieve high sensitivity without sacrificing specificity. Blinded validation with 15 LD-positive and 15 negative samples shows 95.5% sensitivity and 100% specificity. Blind testing with the CDC’s LD repository samples confirms the test accuracy, matching lab-based two-tier results, correctly differentiating between LD and look-alike diseases. This LD diagnostic test could potentially replace the cumbersome two-tier testing, improving diagnosis and enabling earlier treatment while facilitating immune monitoring and surveillance.

Roberto Anichini,1 Sabrina Cosimi,2 Alberto Di Carlo,3 Paola Orsini,4 Alessandra De Bellis,1 Giuseppe Seghieri,1 Flavia Franconi,5 Fabio Baccetti6 1Diabetes Unit, Spedali Riuniti, Pistoia, Italy; 2Diabetes Unit, Hospital of Versilia, Camaiore (LU), Italy; 3Diabetes Unit, Hospital of Lucca, Italy; 4Diabetes Unit, Hospital of Livorno, Italy; 5Department of Biochemical Sciences, University of Sassari, Italy; 6Diabetes Unit, Hospital of Massa, Italy Purpose: To investigate whether gender affects therapeutic response by exenatide twice a day (BID) in type 2 diabetes by using a database concerning patients monitored by five outpatient clinics in Tuscany, Italy. Patients and methods: We considered a cohort of 315 (154 male/161 female) patients experiencing therapeutic failure while on oral therapy (metformin, or combination therapy metformin + sulphonylureas), who were given exenatide (10 µg/BID) and who fully completed 4 months, 8 months, and 12 months of follow-ups. Results: Among patients stratified by gender and well matched for age, body mass index, and hemoglobin A1c (HbA1c), it was found that the length of disease was longer in females than in males (12 ± 8 years versus 10 ± 7 years; P = 0.037), and the ratio of patients on metformin to those on combination therapy was higher in men (P = 0.018). Target glycemic response (1-year HbA1c ≤ 7%) was achieved in a significantly higher proportion of males than females (38% versus 27%;Χ2 = 4.66; P = 0.03). Target weight loss expressed as 1-year weight percent fall from baseline ≥ 75th percentile (8.5%) was significantly higher in females at 8 and 12 months (P < 0.05; for both). One-year glycemic target response was inversely related to baseline HbA1c levels and diabetes duration among males, while metformin therapy (compared to oral combination therapy) was a significant predictor of better glycemic targets among females. Homeostasis model assessment-B, measured in 117 patients, predicted hypoglycemic response only in women (P = 0.009). Target 1-year weight loss was predicted by longer diabetes duration among males and by lower baseline HbA1c among females. Finally, no significant difference between genders was noted as to gastrointestinal side effects after exenatide therapy. Conclusion: According to this “real world” experience, predictors of glycemic control and body weight loss after 12 months of exenatide BID therapy are different between genders in type 2 diabetes. Keywords: GLP-1 agonist therapy, exenatide BID, type 2 diabetes, real world setting

BackgroundOrbital rhabdomyosarcoma (RMS) is often limited to the orbital cavity and has a favorable prognosis. In some cases, the tumor can erode the orbital bone and behave as a parameningeal RMS (PM-RMS); thus, it is treated more intensively. However, the current protocols do not provide any guidance on how to consider different grades of bone erosion (BE) that can vary widely, hampering a uniform classification and the subsequent treatment assignment. With the aim of clarifying the role of BE as a risk factor, we analyzed patients with orbital RMS included in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) protocol.MethodsWe retrospectively analyzed the radiological reports of 199 patients with orbital RMS (PM or not) and defined three grades of BE: minimal (thinning of the bone), moderate (focal bone lysis), and extensive (complete cortical destruction).ResultsBE was present in 55 of the 199 (27.6%) patients, which was classified as minimal in 27, moderate in 7, and extensive in 21. Tumors with extensive BE were more frequently large (>5 cm, p = 0.0008) and invasive (T2, p = 0.001). With a median follow-up of 70.4 months (range = 7.1–167.7), a total of 183 patients are alive, with 5-year event-free survival (EFS) and overall survival (OS) rates of 76% (95%CI = 69.2–81.3) and 92% (95%CI = 86.7–94.8), respectively. Patients without any BE had better OS (95% vs. 81%, p = 0.001), but not EFS. Patients with no/minimal/moderate BE had better EFS and OS compared with patients with extensive BE [EFS of 78.1 (95%CI = 71.1–83.5) vs. 57.1 (95%CI = 33.8–74.9), p = 0.0114, respectively, and OS of 94.0 (95%CI = 89.2–96.8) vs. 71.1 (95%CI = 46.6–85.9), p < 0.0001, respectively]. Events and metastatic relapses (in all cases CNS/meningeal) were more frequent in patients with extensive BE.ConclusionsOnly those patients with orbital RMS and extensive BE should be considered as PM and should be treated accordingly.

IntroductionSalmonella spp. is the second most common bacteria associated with foodborne gastrointestinal outbreaks in humans, with the highest contamination levels in meat, especially poultry. Salmonella enterica subsp. enterica serovar Infantis is the primary serovar isolated from broilers, without causing any symptomatic disease. Conversely, certain human strains can result in symptomatic illness (fever, headache, and diarrhoea). Therefore, reducing S. Infantis colonization in broilers is important before slaughter, to prevent this pathogen carryover along the food chain.MethodsHere, we report the characterization of two S. Infantis virulent phages, isolated from broiler feces. Isolates were phenotypically and genetically characterized.Results and discussionPhages (ɸ) SaI_NFG_5581 and SaI_NFG_5577 were characterized as strictly lytic versus S. Infantis but with different bacteriolytic activities and genetic features. They both belong to the Caudoviricetes class, but ɸSaI_NFG_5581 (genome length 112,970 bp) belongs to the Demerecviridae family while ɸSaI_NFG_5577 (genome length 42,481 bp) to the Guernseyvirinae family. Genomic analysis excluded the presence of lysogeny, toxin, or antimicrobial resistance genes, and for those reasons, the two phages could be considered safe. Phages are stable under a broad range of pH (4-10) and temperature (4°C-50°C) conditions. In vitro, both ɸSaI_NFG_5581 and ɸSaI_NFG_5577 were able to lower Salmonella counts of about 2.2 LOG/mL and 3.4 LOG CFU/mL respectively, at MOI 0.1 after 2 h of treatment. After 24 h, Salmonella counts treated with both phages remained lower than the control (non-phage-treated Salmonella). These newly isolated phages have promising features, which could be exploited and further studied for potential in vivo application.

Background: The “Young NaPHOS” project was launched in 2021, by Young SIOPE, the group for junior members of the European Society for Paediatric Oncology (SIOPE). The Young NaPHOS project aims to build a network of national representatives of young paediatric haematologists and oncologists to discuss organisational and educational aspects at national and European level, differences in the training paths, and the needs to be addressed in the future. Methods: From June 2021 until September 2022, three online meetings took place and one online survey was conducted. The meetings focused on presenting the structure and organisational aspects of existing national junior organisations in paediatric haematology and oncology, including their national activities. The survey aimed to investigate the European landscape of national organisations and training paths by inviting 39 young national representatives. Results: Ten out of 34 responders confirmed the existence of a junior organisation in their country. Diversity was noted among the countries for the existence of such organisations, the organisations’ activities, or the membership criteria. Further, the training path to become a paediatric oncologist/haematologist differs a lot. Young paediatric oncologists also shared common concerns, especially regarding networking, international collaboration, and educational opportunities. Conclusion: This project resulted in the creation of a European network among young paediatric oncologists and haematologists, in spreading ideas and offering support, and identified differences and areas for future action of Young SIOPE.

Introduction: Data-driven research has improved paediatric cancer outcomes for children. However, challenges in sharing data between institutions prevent the use of artificial intelligence (AI) to address substantial unmet needs in children diagnosed with cancer. Harmonising collected data can enable the application of AI for a greater understanding of paediatric cancers. The main goal of the paper was to analyse the currently used childhood cancer databases to identify a core of variables able to capture the most relevant data on the diagnosis and treatment of children and adolescents with cancer. Methods: We arbitrarily identified different types of existing databases dedicated to collecting data of patients with solid tumours, Umbrella, FAR-RMS; PARTNER; ERN PAEDCAN Registry; INSTRUCT and INRG; the common data elements for Rare Disease by Joint Research Centre. The different elements of the CRFs were analysed and ranked “essential” and “good to have”. Domains that included a group of variables structurally connected were identified. Each variable was defined by name, data type, description, and permissible values. Results: We identified six structural domains: Patient registration, Personal information, Disease History, Diagnosis, Treatment, and Follow-up and Events. For each of them, “essential” and “good to have” variables were defined. Discussion: Data harmonisation is essential for enhancing integration and comparability in research. By standardizing data formats and variables, researchers can facilitate data sharing, collaboration, and analysis across multiple studies and datasets. Embracing data harmonization practices will advance application of AI, scientific knowledge, improve research reproducibility, and contribute to evidence-based decision-making in various fields.