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Abstract Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology is a groundbreaking and dynamic molecular tool for DNA and RNA “surgery”. CRISPR/Cas9 is the most widely applied system in oncology research. It is a major advancement in genome manipulation due to its precision, efficiency, scalability and versatility compared to previous gene editing methods. It has shown great potential not only in the targeting of oncogenes or genes coding for immune checkpoint molecules, and in engineering T cells, but also in targeting epigenomic disturbances, which contribute to cancer development and progression. It has proven useful for detecting genetic mutations, enabling the large-scale screening of genes involved in tumor onset, progression and drug resistance, and in speeding up the development of highly targeted therapies tailored to the genetic and immunological profiles of the patient’s tumor. Furthermore, the recently discovered Cas12 and Cas13 systems have expanded Cas9-based editing applications, providing new opportunities in the diagnosis and treatment of cancer. In addition to traditional cis-cleavage, they exhibit trans-cleavage activity, which enables their use as sensitive and specific diagnostic tools. Diagnostic platforms like DETECTR, which employs the Cas12 enzyme, that cuts single-stranded DNA reporters, and SHERLOCK, which uses Cas12, or Cas13, that specifically target and cleave single-stranded RNA, can be exploited to speed up and advance oncological diagnostics. Overall, CRISPR platform has the great potential to improve molecular diagnostics and the functionality and safety of engineered cellular medicines. Here, we will emphasize the potentially transformative impact of CRISPR technology in the field of oncology compared to traditional treatments, diagnostic and prognostic approaches, and highlight the opportunities and challenges raised by using the newly introduced CRISPR-based systems for cancer diagnosis and therapy.

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.

Background: Arterial embolization is a minimally invasive treatment that occludes blood vessels supplying pathological tissue. Developed to control bleeding without surgery, it has evolved over decades and is now applied in musculoskeletal oncology as a preoperative treatment, palliative care, or standalone therapy for select tumors. Recently, its use has expanded globally in treating chronic pain syndromes and osteoarthritis. Materials and Methods: We reviewed the literature on arterial embolization in various musculoskeletal conditions. The focus was on established oncologic indications for primary and metastatic bone or soft tissue tumors, and emerging evidence on degenerative diseases like osteoarthritis, inflammatory musculoskeletal pathology, and intractable pain. Emphasis was placed on leading studies regarding efficacy, complications, and recurrence rates. Discussion: Arterial embolization has progressed from bleeding control to a versatile therapeutic option in musculoskeletal medicine. It offers symptom relief, reduces tumor size, and improves quality of life. Applications include oncologic interventions and management of degenerative and inflammatory conditions. Despite its benefits, variations in complications and recurrence rates highlight the need for standardized protocols and further research. Conclusions: Arterial embolization is a safe and effective minimally invasive tool in the multidisciplinary management of a wide range of musculoskeletal pathologies. Ongoing research is crucial to understand long-term efficacy, optimize protocols, and broaden its applications.

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.

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.

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.

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 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 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 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 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 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.

Abstract Precipitation is a critical part of the global hydrological cycle that determines the distribution of water resources. It is also an essential meteorological variable used as input for hydroclimatic models and projections. However, precipitation data frequently lack complete series, especially at daily and sub‐daily precipitation stations, which are usually large, bulky, and complex. To address this, gap filling is commonly used to produce complete hydrometeorological data series without missing values. Several gap‐filling methods have been developed and improved. This study seeks to fill the gaps of 201 daily precipitation time series in Central Italy by localizing the approach used to generate the Serially Complete dataset for the Planet Earth (SC‐Earth). This method combines the outcome of 15 strategies based on four various gap‐filling techniques (quantile mapping, spatial interpolation, machine learning, and multi‐strategy merging). These strategies employ the daily dataset of the neighbouring stations and the matched ERA5 data to estimate missing values at the target stations. Both raw data and the final serially complete station datasets (SCDs) underwent comprehensive quality control. Many accuracy indicators have been utilized to evaluate the performance of the strategies' estimations and the final SCD, such as Correlation Coefficient (CC), Root mean square error (RMSE), Relative bias (Bias %), and Kling‐Gupta efficiency (KGE″). Multi‐strategy merging strategy based on the Modified Kling‐Gupta efficiency (MS1) shows the highest performance as an individual precipitation gap‐filling strategy. However, the machine learning strategy using random forest (ML3) has the most outstanding share in the final estimates among all other strategies. In the end, the temporal–spatial performance of the final SCD is promising and depends on the pattern of the missing values (MV%). The mean values of KGE″, CC, variability (α), and bias term (β) are 0.9, 0.93, 1.064, and 4.98 × 10−7, respectively.

Drawing language maps is not normally considered an important part of linguists’ work. Nonetheless, language maps influence their users’ perceptions and understandings of the characteristics of the languages that they represent. Therefore, given their communicative power, wide accessibility, and generalized use for educational purposes, attention must be paid as to what messages language maps convey about the languages that they visualize since different cartographic styles can be suited to representing some language ecologies better than others. However, decisions at this level are not normally made explicit by cartographers, and the ways in which certain ideologies surface in language maps can escape the attention of both linguists and cartographers alike. This article clarifies why these issues are especially relevant in a domain such as that of the study of Bantoid languages and proposes some novel cartographic models that have been used for representing the languages of Lower Fungom in western Cameroon. These include some cartographic strategies for the representation of the language ideologies of speaker communities and of individual multilingualism. The latter is both a key and under-researched feature in Bantoid sociolinguistics and the article suggests how scholars who are not sociolinguists may nevertheless contribute to its exploration.

Introduction: Image and performance-enhancing drugs (IPEDs), or lifestyle drugs, are a wide range of products presented as having the potential to improve mental and physical function and health. Little is known about IPEDs consumption during the COVID-19 lockdown. The present study aimed to profile IPEDs during this period characterised by physical distancing, isolation, gym closures, and other altered lifestyle habits. Methods: A cross-sectional observational study investigating the type of IPEDs consumed and purchasing methods was disseminated via a web-based questionnaire in eight countries (United Kingdom, Italy, Lithuania, Hungary, Portugal, Spain, Brazil, and Japan) between April and May 2020. This included the Exercise Addiction Inventory (EAI), the Appearance Anxiety Inventory (AAI), and the Self-Compassion Scale (SCS). Results: A total of 736 IPEDs users were included in the survey. The mean age of the sample was 33.05 years (SD =10.06), with females rate of 64.2%. Among IPEDs users, 6.8% were at risk of exercise addiction (EAI >24), 27.6% presented high levels of appearance anxiety and 24.9% revealed low levels of self-compassion and emotional self-regulation. Most participants (55.6%) purchased IPEDs through pharmacies/specialised shops, while 41.3% purchased IPEDs on the Internet. Online shoppers of IPEDs were mainly men who reported higher scores on the Exercise Addiction Inventory. One or more IPEDs classifiable as “potentially at-risk” were used by 66.3% of the sample. Users of “potentially at-risk IPEDs” were younger and mostly males. They showed higher scores both at Exercise Addiction Inventory and Appearance Anxiety Inventory. Conclusions: This study profiled users of IPEDs during the peak of lockdown policies due to the COVID-19 breakdown. Both purchasing methods and types of IPEDs consumed were associated with distinct socio-demographic aspects and psychopathological traits. Some relevant cross-cultural differences were highlighted. Longitudinal studies will be needed to determine the impact of the COVID-19 lockdown on IPEDs consumption.

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.

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.

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.

Urologic patients with anatomic abnormalities can be particularly susceptible to urinary tract infections (UTI). UTI with urease-producing bacteria can promote struvite urinary calculi and pose unique treatment problems. There is potential for rapid stone growth and bacterial eradication can be difficult secondary to urothelial or stone colonization. Antibiotic resistance among urease-producing organisms further complicates treatment. In this report, we describe the use of intravesical vancomycin in the treatment of a patient with struvite bladder calculi secondary to urease-producing Corynebacterium urealyticum cystitis, resistant to enteral antibiotics. This highlights the potential of intravesical antibiotics for the treatment of UTI.

Abstract Cancer is a leading cause of morbidity and mortality worldwide, and an increase in incidence is estimated in the next future, due to population aging, which requires the development of highly tolerable and low‐toxicity cancer treatment strategies. The use of nanotechnology to tailor treatments according to the genetic and immunophenotypic characteristics of a patient's tumor, and to allow its targeted release, can meet this need, improving the efficacy of treatment and minimizing side effects. Nanomedicine‐based approach for the diagnosis and treatment of cancer is a rapidly evolving field. Several nanoformulations are currently in clinical trials, and some have been approved and marketed. However, their large‐scale production and use are still hindered by an in‐depth debate involving ethics, intellectual property, safety and health concerns, technical issues, and costs. Here, we survey the key approaches, with specific reference to organ‐on chip technology, and cutting‐edge tools, such as CRISPR/Cas9 genome editing, through which nanosystems can meet the needs for personalized diagnostics and therapy in cancer patients. An update is provided on the nanopharmaceuticals approved and marketed for cancer therapy and those currently undergoing clinical trials. Finally, we discuss the emerging avenues in the field and the challenges to be overcome for the transfer of nano‐based precision oncology into clinical daily life.

Abstract Critical challenges remain in clinical translation of extracellular vesicle (EV)-based therapeutics due to the absence of methods to enrich cells with high EV secretion. Current cell sorting methods are limited to surface markers that are uncorrelated to EV secretion or therapeutic potential. Here, we utilize a nanovial technology for enrichment of millions of single cells based on EV secretion. This approach is applied to select mesenchymal stem cells (MSCs) with high EV secretion as therapeutic cells for improving treatment. The selected MSCs exhibit distinct transcriptional profiles associated with EV biogenesis and vascular regeneration and maintain high levels of EV secretion after sorting and regrowth. In a mouse model of myocardial infarction, treatment with high-secreting MSCs improves heart functions compared to treatment with low-secreting MSCs. These findings highlight the therapeutic importance of EV secretion in regenerative cell therapies and suggest that selecting cells based on EV secretion could enhance therapeutic efficacy.

Abstract Detection of high glycated hemoglobin (A1c) is associated with worse postoperative outcomes, including predisposition to develop systemic and local infectious events. Diabetes and infectious Outcomes in Cardiac Surgery (DOCS) study is a retrospective case–control study aimed to assess in DM and non-DM cardiac surgery patients if a new screening and management model, consisting of systematic A1c evaluation followed by a specialized DM consult, could reduce perioperative infections and 30-days mortality. Effective July 2021, all patients admitted to the cardiac surgery of IRCCS ISMETT were tested for A1c. According to the new protocol, glucose values of patients with A1c ≥ 6% or with known diabetes were monitored. The diabetes team was activated to manage therapy daily until discharge or provide indications for the diagnostic-therapeutic process. Propensity score was used to match 573 patients managed according to the new protocol (the Screen+ Group) to 573 patients admitted before July 2021 and subjected to the traditional management (Screen−). Perioperative prevalence of infections from any cause, including surgical wound infections (SWI), was significantly lower in the Screen+ as compared with the Screen− matched patients (66 [11%] vs. 103 [18%] p = 0.003). No significant difference was observed in 30-day mortality. A1c analysis identified undiagnosed DM in 12% of patients without known metabolic conditions. In a population of patients undergoing cardiac surgery, systematic A1c evaluation at admission followed by specialist DM management reduces perioperative infectious complications, including SWI. Furthermore, A1c screening for patients undergoing cardiac surgery unmasks unknown DM and enhances risk stratification.

In the last decades the mush model has been generalized to the complete trans-crustal magmatic system in which differentiation would be driven by segregation and extraction of trapped melts from crystal-rich mushes. Melt extraction processes involved are porous flow and strain localization, the latter being regarded as the main process acting during transfer through dykes and necks along which high differential stresses are acting on. We combine structural measurements together with petrological analyses and textural observations to constrain the model of emplacement and finally emphasize how shear deformation and strain localization structures promoted the residual melt segregation that occurred in a shallow silica-undersaturated peralkaline intrusion (Suc de Sara, Velay volcanic province, French Massif Central). In this study, we demonstrate that segregation and subsequent extraction of the CO2-rich residual melt occurred during magma ascent and final emplacement of the Suc de Sara tinguaite. Contrasting features of shear deformation between the margins that exhibited different permeabilities highlight that melt segregation started by compaction as a loose packing of emerging microlites and continued with melt filling of an anastomosed C/C′ band network developing in the crystal-rich mush subjected to high shear strain. Subsequent melt extraction throughout the country rock was controlled by the permeability of the hanging wall. Along the western hanging wall of the intrusion, extraction of the residual melt was prevented by the 15 cm thick chilled margin. In contrast, segregated melt circulated through the highly porous and permeable eastern margin, causing the fenitization of the country rock.

Abstract Background The trauma mortality rate is higher in the elderly compared with younger patients. Ageing is associated with physiological changes in multiple systems and correlated with frailty. Frailty is a risk factor for mortality in elderly trauma patients. We aim to provide evidence-based guidelines for the management of geriatric trauma patients to improve it and reduce futile procedures. Methods Six working groups of expert acute care and trauma surgeons reviewed extensively the literature according to the topic and the PICO question assigned. Statements and recommendations were assessed according to the GRADE methodology and approved by a consensus of experts in the field at the 10th international congress of the WSES in 2023. Results The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage, including drug history, frailty assessment, nutritional status, and early activation of trauma protocol to improve outcomes. Acute trauma pain in the elderly has to be managed in a multimodal analgesic approach, to avoid side effects of opioid use. Antibiotic prophylaxis is recommended in penetrating (abdominal, thoracic) trauma, in severely burned and in open fractures elderly patients to decrease septic complications. Antibiotics are not recommended in blunt trauma in the absence of signs of sepsis and septic shock. Venous thromboembolism prophylaxis with LMWH or UFH should be administrated as soon as possible in high and moderate-risk elderly trauma patients according to the renal function, weight of the patient and bleeding risk. A palliative care team should be involved as soon as possible to discuss the end of life in a multidisciplinary approach considering the patient’s directives, family feelings and representatives' desires, and all decisions should be shared. Conclusions The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage based on assessing frailty and early activation of trauma protocol to improve outcomes. Geriatric Intensive Care Units are needed to care for elderly and frail trauma patients in a multidisciplinary approach to decrease mortality and improve outcomes. Graphical abstract

Abstract Perovskite solar cells promise to be part of the future portfolio of photovoltaic technologies, but their instability is slow down their commercialization. Major stability assessments have been recently achieved but reliable accelerated ageing tests on beyond small-area cells are still poor. Here, we report an industrial encapsulation process based on the lamination of highly viscoelastic semi-solid/highly viscous liquid adhesive atop the perovskite solar cells and modules. Our encapsulant reduces the thermomechanical stresses at the encapsulant/rear electrode interface. The addition of thermally conductive two-dimensional hexagonal boron nitride into the polymeric matrix improves the barrier and thermal management properties of the encapsulant. Without any edge sealant, encapsulated devices withstood multifaceted accelerated ageing tests, retaining >80% of their initial efficiency. Our encapsulation is applicable to the most established cell configurations (direct/inverted, mesoscopic/planar), even with temperature-sensitive materials, and extended to semi-transparent cells for building-integrated photovoltaics and Internet of Things systems.

This paper sheds light on the manufacturing processes, techniques, and materials used in the splendid illuminations of the oldest surviving copy of De Balneis Puteolanis, preserved at the Angelica Library in Rome (Ms. 1474). The codex is one of the masterpieces of mid-13th-century Italian-Southern illumination, traditionally referred to as the commission of Manfredi, son of Frederick II. The findings reported in the article result from the interdisciplinary study conducted in 2021–2023 in the framework of “Codex 4D: journey in four dimensions into the manuscript”, a multidisciplinary project involving many competences and dealing with art-historical studies on manuscripts, diagnostic and conservative analyses, scientific dissemination, storytelling, and public engagement. The considerations we present aims at increasing the knowledge of book artefacts while respecting their extraordinary complexity; data from non-invasive diagnostic investigations (X-ray fluorescence, Vis-NIR reflectance and Raman spectroscopies, hyperspectral imaging, and multi-band imaging techniques as ultraviolet, reflectography, and thermography), carried out in situ with portable instruments on the book, have been integrated with observations resulting from the historical-artistic study, and the reading of some ancient treatises on the production and use of the pigments and dyes employed in illumination.

Abstract The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.

Background: Oligo-metastatic disease (OMD) in colon cancer patients exhibits distinct clinical behavior compared to poly-metastatic disease (PMD), with a more responsive and indolent course. This study aims to identify clinical and biological factors uniquely associated with oligo-metastatic behavior. Methods: Metastatic colon cancer patients from an academic center underwent genetic characterization. OMD was defined as ≤3 lesions per organ, each with a total diameter 70 vs.

Abstract Purpose The aim of this study was to quantify meniscal extrusion through ultrasound (US) evaluation in supine and standing positions and to compare the results with those documented through magnetic resonance (MR) imaging in patients affected by knee osteoarthritis (OA). Methods Sixty patients (38 men, 22 women, mean age 60.8 ± 9.7 years) with knee OA were enrolled and underwent a 1.5 T MR evaluation and an US examination of the symptomatic OA knee for the evaluation of the medial and lateral meniscus extrusion both in the supine clinostatic position (clino‐US) with the knee fully extended and in the standing weight‐bearing orthostatic position (ortho‐US). For the three imaging evaluations (MR, clino‐US and ortho‐US), both semi‐quantitative and quantitative measurements were performed. Results The quantitative analysis documented higher values of medial meniscal extrusion at the ortho‐US evaluation (5.2 ± 2.3 mm) compared to MR (4.2 ± 2.2, p

Insulin autoimmune syndrome or Hirata's disease is a rare condition characterized by hypoglycemia associated with endogenous autoimmune hyperinsulinism. This report concerns the case of a 28-year-old Latin American woman with Graves' disease who developed insulin autoimmune syndrome and then subsequently became pregnant. She displayed symptoms related to severe hypoglycemia due to hyperinsulinemia, elevated C-peptide, and anti-insulin antibodies. Prior to pregnancy she was treated with corticosteroids and had ablative treatment with iodine-131. During follow-up of both conditions, the patient became pregnant, and clinically and biochemically hyperthyroid, for which total thyroidectomy was performed during the second trimester of pregnancy. Anti-insulin antibodies, blood glucose, and C-peptide remained normal throughout pregnancy. At 40 weeks of gestation she gave birth to a healthy female newborn with normal blood glucose values. Molecular genetic analysis determined the following genotypes: HLA-DRB1*03:01 / HLA-DRB1*04:01 in the mother; and HLA-DRB1*04:01 / HLA-DRB1*08:02 in the daughter. Because some HLA-DRB1*04 alleles are associated with susceptibility to insulin autoimmune syndrome induced by environmental factors, the patient was advised regarding the future use of drugs with a sulfhydryl group and possible triggering factors for insulin autoimmune syndrome. At 6-month follow-up the daughter presented normal growth and development, as well as normal plasma glucose values, and this remained the case at five-year follow-up.

The oviduct plays a crucial role in the reproductive process, serving as the stage for fertilization and the early stages of embryonic development. When the environment of this organ has been mimicked, it has been shown to enhance in vitro embryo epigenetic reprogramming and to improve the yield of the system. This study explores the anatomical intricacies of two oviduct regions, the uterotubal junction (UTJ) and the ampullary-isthmic junction (AIJ) by using micro-computed tomography (MicroCT). In this study, we have characterized and 3D-reconstructed the oviduct structure, by measuring height and width of the oviduct’s folds, along with the assessments of fractal dimension, lacunarity and shape factor. Results indicate distinct structural features in UTJ and AIJ, with UTJ displaying small, uniformly distributed folds and high lacunarity, while AIJ shows larger folds with lower lacunarity. Fractal dimension analysis reveals values for UTJ within 1.189–1.1779, while AIJ values range from 1.559–1.770, indicating differences in structural complexity between these regions. Additionally, blind sacs or crypts are observed, akin to those found in various species, suggesting potential roles in sperm sequestration or reservoir formation. These morphological differences align with functional variations and are essential for developing an accurate 3D model. In conclusion, this research provides information about the oviduct anatomy, leveraging MicroCT technology for detailed 3D reconstructions, which can significantly contribute to the understanding of geometric-morphological characteristics influencing functional traits, providing a foundation for a biomimetic oviduct-on-a-chip.

Radon is a natural and radioactive noble gas, which may accumulate indoors and cause lung cancers after long term-exposure. Being a decay product of Uranium 238, it originates from the ground and is spatially variable. Many environmental (i.e., geology, tectonic, soils) and architectural factors (i.e., building age, floor) influence its presence indoors, which make it difficult to predict. However, different methods have been developed and applied to identify radon prone areas and buildings. This paper presents the results of a systematic literature review of suitable statistical methods willing to identify buildings and areas where high indoor radon concentrations might be found. The application of these methods is particularly useful to improve the knowledge of the factors most likely to be connected to high radon concentrations. These types of methods are not so commonly used, since generally statistical methods that study factors predictive of radon concentration are focused on the average concentration and aim to identify factors that influence the average radon level. In this paper, an attempt has been made to classify the methods found, to make their description clearer. Four main classes of methods have been identified: descriptive methods, regression methods, geostatistical methods, and machine learning methods. For each presented method, advantages and disadvantages are presented while some applications examples are given. The ultimate purpose of this overview is to provide researchers with a synthesis paper to optimize the selection of the method to identify radon prone areas and buildings.

Objective. To describe an intensive and multimodal ultrasound (US) training program focused on Achilles enthesitis and to illustrate the learning curve of trainees without experience. Methods. Three medical students (trainees) and two rheumatologists experienced in musculoskeletal US (trainers) were involved in the training program, which encompassed one preliminary theoretical-practical meeting and five scanning sessions (two patients per session). The students and one expert performed the US examination of the Achilles enthesis bilaterally. The trainees acquired representative images and assessed the presence of Outcome Measures in Rheumatology (OMERACT) US abnormalities of enthesitis. The experts provided feedback addressing trainees’ misinterpretations, and the quality of the acquired images was evaluated. A dedicated questionnaire was used to evaluate the students’ confidence. After each session, five sets of static images (total=100 images of most commonly scanned entheses) were provided and scored by the students according to OMERACT US definitions. Total agreement and prevalence and bias adjusted kappa (PABAK) were used to evaluate the concordance between the trainees and the expert sonographer. Results. The total agreement and PABAK significantly improved between the first and fifth scanning sessions (76.2% versus 92.9%, p

After harvesting of cones used for beer production, the remaining hop vegetative biomass requires disposal. The hop plant contains bioactive compounds in all its parts—cones, leaves, and roots—exhibiting interesting antioxidant, antiviral, and antibacterial properties. In this work, extracts obtained from hop leaves, a plant material often neglected in the hop cultivation, have been investigated; the qualitative UHPLC-MS/MS and GC-TOF-MS characterization revealed the presence of bioactive compounds such as polyphenols, α- and β-acids and terpenes are present. The extract retained antioxidant activity, as verified by Folin-Ciocalteu, DPPH, ABTS and FRAP assays, and demonstrated some antimicrobial activity when combined with antibiotics, particularly against Gram-positive bacterial strains. Additionally, the extracts showed an ability to interact with proteins as human insulin, amyloid beta peptide, mucin and bovine serum albumin (BSA), has been detected, indicating their potential to counteract inflammatory processes and protect against Alzheimer's disease. These findings suggest that hop vegetative biomass, typically considered waste, can be potentially transformed into a valuable resource with applications in various fields, from nutraceuticals to pharmaceuticals and cosmetics, aligning with a circular economy perspective.

We propose to investigate the time modulation of radioisotope decays deep underground as a method to explore axion dark matter. In this work, we focus on the α-decay of heavy isotopes and develop a theoretical description for the θ-dependence of α-decay half-lives, which enables us to predict the time variation of α-radioactivity in response to an oscillating axion dark matter background. To probe this scenario, we have recently constructed and installed a setup deep underground at the Gran Sasso Laboratory, based on the α-decay of Americium-241. This prototype experiment, named RadioAxion-α, will allow us to explore a broad range of oscillation's periods, from a micro-second up to one year, thus providing competitive limits on the axion decay constant across 13 orders of magnitude in the axion mass, ranging from 10−9 eV to 10−20 eV after one month of data collection, and down to 10−22 eV after three years.

Abstract Background The Biology System Description Language (BiSDL) is an accessible, easy-to-use computational language for multicellular synthetic biology. It allows synthetic biologists to represent spatiality and multi-level cellular dynamics inherent to multicellular designs, filling a gap in the state of the art. Developed for designing and simulating spatial, multicellular synthetic biological systems, BiSDL integrates high-level conceptual design with detailed low-level modeling, fostering collaboration in the Design-Build-Test-Learn cycle. BiSDL descriptions directly compile into Nets-Within-Nets (NWNs) models, offering a unique approach to spatial and hierarchical modeling in biological systems. Results BiSDL’s effectiveness is showcased through three case studies on complex multicellular systems: a bacterial consortium, a synthetic morphogen system and a conjugative plasmid transfer process. These studies highlight the BiSDL proficiency in representing spatial interactions and multi-level cellular dynamics. The language facilitates the compilation of conceptual designs into detailed, simulatable models, leveraging the NWNs formalism. This enables intuitive modeling of complex biological systems, making advanced computational tools more accessible to a broader range of researchers. Conclusions BiSDL represents a significant step forward in computational languages for synthetic biology, providing a sophisticated yet user-friendly tool for designing and simulating complex biological systems with an emphasis on spatiality and cellular dynamics. Its introduction has the potential to transform research and development in synthetic biology, allowing for deeper insights and novel applications in understanding and manipulating multicellular systems.

Abstract Kaon physics is at a turning point – while the rare-kaon experiments NA62 and KOTO are in full swing, the end of their lifetime is approaching and the future experimental landscape needs to be defined. With HIKE, KOTO-II and LHCb-Phase-II on the table and under scrutiny, it is a very good moment in time to take stock and contemplate about the opportunities these experiments and theoretical developments provide for particle physics in the coming decade and beyond. This paper provides a compact summary of talks and discussions from the Kaons@CERN 2023 workshop, held in September 2023 at CERN.

Highlights Self-powered direct X-ray detectors, based on FAPbBr3 255-nm-thick films deposited onto mesoporous TiO2 scaffolds, can withstand a 26-day uninterrupted X-ray exposure with negligible signal loss, demonstrating ultra-high operational stability. Bulk specific sensitivity is evaluated to be 7.28 C Gy−1 cm−3 at 0 V, an unprecedented value in the field of thin-film-based photoconductors and photodiodes for “hard” X-rays. Sensitivity of submicrometer-thick perovskite films to the X-rays produced by a medical linear accelerator used for cancer treatment is here demonstrated for the first time.

Abstract Primary human trophoblast stem cells (TSCs) and TSCs derived from human pluripotent stem cells (hPSCs) can potentially model placental processes in vitro. Yet, the pluripotent states and factors involved in the differentiation of hPSCs to TSCs remain poorly understood. In this study, we demonstrate that the primed pluripotent state can generate TSCs by activating pathways such as Epidermal Growth Factor (EGF) and Wingless-related integration site (WNT), and by suppressing tumor growth factor beta (TGFβ), histone deacetylases (HDAC), and Rho-associated protein kinase (ROCK) signaling pathways, all without the addition of exogenous Bone morphogenetic protein 4 (BMP4)—a condition we refer to as the TS condition. We characterized this process using temporal single-cell RNA sequencing to compare TS conditions with differentiation protocols involving BMP4 activation alone or BMP4 activation in conjunction with WNT inhibition. The TS condition consistently produced a stable, proliferative cell type that closely mimics first-trimester placental cytotrophoblasts, marked by the activation of endogenous retroviral genes and the absence of amnion expression. This was observed across multiple cell lines, including various primed induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) lines. Primed-derived TSCs can proliferate for over 30 passages and further specify into multinucleated syncytiotrophoblasts and extravillous trophoblast cells. Our research establishes that the differentiation of primed hPSCs to TSC under TS conditions triggers the induction of TMSB4X, BMP5/7, GATA3, and TFAP2A without progressing through a naive state. These findings propose that the primed hPSC state is part of a continuum of potency with the capacity to differentiate into TSCs through multiple routes.

The success of dental implant placement and prosthetic reconstruction relies on sufficient bone volume at the implant site. Contemporary implantology integrates prosthetic planning with implant placement, emphasizing the importance of pre-established prosthetic goals. Guided Bone Regeneration (GBR) techniques have become crucial for bone reconstruction. This study explores the use of custom-made GBR membranes, designed through CAD-CAM technology, in 10 patients with severe bone defects. Patients underwent meticulous preoperative planning, in which digital diagnostic wax-ups and RealGUIDE™ software for implant positioning were used. The custom-made membranes, which were designed based on the individual defects, exhibited successful adaptation. Surgical phases involved membrane placement, bone grafting, and subsequent implant placement. Clinical–radiographic follow-ups demonstrated favorable bone gain outcomes, which enabled prosthetic rehabilitation. Despite membrane exposure occurring in 30% of cases, it did not compromise overall success. The study underscores the potential of custom-made GBR membranes in achieving prosthetic goals, though challenges like exposure and the need for a second surgery require further investigations. The results indicate a promising alternative for predictable bone regeneration in complex cases, shedding light on the prosthetically guided approach for optimal functional and aesthetic outcomes.

Background: During the time-course of cognitive decline, Behavioral and Psychological Symptoms of Dementia (BPSD) may arise, negatively impacting the outcomes. Methods: The aim of this single center, longitudinal study was to evaluate the correlation between frailty and BPSD in a population of older patients with dementia. BPSD were classified into three clusters: “mood/apathy” (depression, apathy, sleep disturbances, appetite disturbances), “psychosis” (delusions, hallucinations, and anxiety), and “hyperactivity” (agitation, elation, motor aberrant behavior, irritability, disinhibition). Using the Clinical Frailty Scale (CFS), patients were categorized as “severely frail”, “mild/moderately frail” and “robust” (CFS ≥ 7, 4–6, and ≤ 3, respectively). Results: In total, 209 patients (mean age 83.24 ± 4.98 years) with a clinical diagnosis of dementia were enrolled. BPSD were prevalent among the severely frail patients. A positive correlation at regression analysis was found between frailty and “hyperactivity” cluster at baseline and follow-up visits (p < 0.001, p = 0.022, p = 0.028, respectively), and was confirmed at the network analysis. Loss of independence in IADL was correlated to hyperactivity and psychosis symptoms (p < 0.001 and p = 0.013, respectively). Conclusions: Scarce literature is available regarding the correlation between frailty and BPSD, which in our study is significant, especially for symptoms in the hyperactivity cluster. Frailty assessment may help identify patients at the highest risk for developing BPDS who might benefit from targeted intervention in the earliest phases of the disease.

Background and Objectives: Functional rehabilitation in patients with hemimandibulectomy remains a challenge no matter what method of reconstruction is chosen by physicians. In this paper, we aim to evaluate the feasibility of an acceptable occlusal restoration in patients who have undergone hemimanidublectomy without the reestablishment of mandibular continuity. Materials and Methods: Data were collected retrospectively on 10 patients with varying degrees of mandible resection. The greatest challenge in the restoration of an acceptable occlusion form is the natural latero-deviation that occurs in patients whose mandibular continuity was not restored. This causes an unbalanced and uncoordinated occlusal plane. Based on our research, this deviation is highly dependent on three main factors: the presence of teeth (which allow for a proprioceptive stimulus that counteracts the deviation), the extension of the defect and the presence or lack of the coronoid process. Results: Based on the presence of dental elements or lack thereof, patients were either rehabilitated with implant-supported dentures or removable partial dentures. Although the gold standard of care for these patients remains the restoration of mandible continuity through use of bone grafts, an acceptable rehabilitation of occlusion and therefore function may be acquired in non-grafted patients. Conclusions: Both physicians and patients must manage their expectations carefully and be eager to find a compromise to provide the best possible solution given the challenges of the premises.

Background and Clinical Significance: We wished to review the use of arterial embolization with n-butyl-cyanoacrylate (NBCA) to treat large high-flow vascular malformations due to its rapid polymerization and ability to permanently occlude large and small vessels. Case Presentation: A 52-year-old male presented with a two-year history of progressively worsening pain and swelling in the right gluteal area. Imaging techniques (color Doppler ultrasonography, CT, DSA, and MRI) were utilized for the diagnosis of a large high-flow intramuscular hemangioma. The mass displaced the surrounding tissues but showed no signs of lymphadenopathy or distant metastasis. The treatment involved targeting different arterial feeders over several sessions. Each procedure used NBCA–Lipiodol under fluoroscopic guidance, progressively reducing the malformation’s size and alleviating his symptoms. After the final embolization, the patient showed significant pain relief and a reduction in the size of the malformation, confirmed by follow-up imaging, demonstrating NBCA embolization’s effectiveness. The protocol’s safety and efficacy in this context are discussed. Conclusions: Arterial embolization with NBCA is a promising treatment for large high-flow vascular malformations, providing symptom relief and reductions in lesion size. While this case report highlights the procedure’s efficacy, further research is needed for a broader understanding of its long-term outcomes and potential complications.

The integrity of the glomerular filtration barrier maintains protein excretion below 150 mg/day. When urinary proteins increase, this indicates damage to the filtration barrier. However, proteinuria is not only a marker of kidney damage but also exacerbates it through various mechanisms involving the glomerular and tubulointerstitial compartments. Therefore, it is essential to intervene with renoprotective action that reduces the proteinuria. In this context, Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are cornerstone treatments. Recent advancements include sodium–glucose cotransporter 2 inhibitors, initially used for glycemic control, now recognized for their renoprotective properties in both diabetic and non-diabetic populations. Another drug, Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has emerged as a promising agent, offering anti-inflammatory and antifibrotic benefits with fewer side effects than traditional steroidal options. Finally, dual inhibition of angiotensin II and endothelin-1 receptors through agents like Sparsentan presents a novel approach with significant antiproteinuric effects in IgA nephropathy and focal segmental glomerulosclerosis. This brief review summarizes the mechanisms by which proteinuria promotes kidney damage and the renoprotective therapeutic approaches available, which can be combined with lifestyle modifications and specific treatments for underlying diseases to mitigate the progression of chronic kidney disease.

The hot gas cleaning and conditioning unit represents a crucial step in the biomass gasification process to achieve the quality of the syngas required for downstream processes. Catalyst-filled filter candles can be used to convert tar and remove particulate matter. In this work, a laboratory-scale packed bed reactor was used to evaluate the performance of a novel patented Ni-based tar reforming catalyst (C&CS #1050 B). To simulate the impurities of the syngas, a solution of naphthalene, toluene and thiophene (as equivalent H2S) was selected. The steam reforming tests were carried out with a tar content of 13 g/Nm3, two gas hourly space velocities (6000 and 13000 h-1), two thiophene contents (equivalent to 50 and 100 ppmv of H2S) and temperatures ranging between 650 and 800 °C. Superior catalytic performance was observed at 50 ppmv (from 700 to 800 °C) compared to a commercial catalyst at GHSV of 6000 h-1. Furthermore, a conversion rate of 100 % was achieved at each temperature even with an H2S content of 100 ppmv. Although tests at higher GHSV (13000 h-1) have shown worst conversion results, the tar conversion rate was higher than shown by the previously tested commercial catalyst (close to 100% at 800°C and above 95 % at 750 °C). Finally, based on the results, a relative low temperature (650 °C) is sufficient to achieve complete tar conversion even at 100 ppmv of thiophene. These results open up the exploitation of the new catalyst in the sorption enhanced gasification processes where low temperatures are required.

In hot gas cleaning of biomass gasification gas conversion results of a fixed bed MgO-NiO catalyst tested in a simulated biomass gasification gas at a naphthalene inlet content of 5 g / Nm3 in the presence of 100 ppmv H2S have shown so far, that catalytic filtration is feasible, if a temperature of 800°C and a space velocity of 3054 or 3207 h-1, respectively, is applied by integrating the catalyst in the cylindrical hollow space of a hot gas filter candle. In this work a novel patented tar reforming catalyst C&CS #1050 B is presented that exhibits a distinctly superior catalytic performance in direct comparison at a total model tar content of 13 g / Nm3. Complete conversion at a space velocity of 6000 h-1 from 750°C down to 650°C was measured because of its more than 4-fold higher NiO density in a fixed bed compared to the MgO-NiO catalyst and its approx. 3.5 – 4.5 times higher BET surface area compared to typical commercial steam reforming catalysts. Due to its 21-fold higher NiO density compared to a catalyst integrated in a filter candle as catalytic layer, fixed bed based catalytic filter candles are superior to candles of catalytic layer design. Based on the evidence of 99% model tar conversion at 750°C also at a content of 4.9 g / Nm3 naphthalene and 9.3 g / Nm3 toluene of a C&CS #1050 B filled candle of 60 mm outer diameter complete real tar abatement with a capacity of 13 g / Nm3 is estimated at this temperature allowing a more energy-efficient hot gas filtration and enlarging the applicability of catalytic hot gas filters to higher tar inlet contents.

BackgroundImage and Performance-Enhancing Drugs (IPEDs) can enhance mental and physical capabilities and impact one’s overall health. Initially confined in sport environments, IPEDs use has become increasingly widespread in a high-performing society. The present study was aimed at profiling IPEDs use during the COVID-19 lockdown among an international sample of young adults.MethodsA cross-sectional observational study was carried out in eight countries (United Kingdom, Italy, Lithuania, Hungary, Portugal, Spain, Brazil, and Japan) between April and May 2020. The survey questionnaire included validated measurements such as Exercise Addiction Inventory (EAI), Appearance Anxiety Inventory (AAI), and Self-Compassion Scale (SCS) as well as questions about the type of IPEDs, purchasing methods and socio-demographic information.ResultsA total of 736 IPEDs users were included in the survey. Their mean age was 33.05 years (±SD = 10.06), and 64.2% were female participants. Overall, 6.8% were found at risk of exercise addiction (EAI >24), 27.6% presented high levels of appearance anxiety, and 24.9% revealed low levels of emotional regulation’s self-compassion. Most participants (55.6%) purchased IPEDs through pharmacies/specialized shops, while 41.3% purchased IPEDs on the Internet. Online IPEDs buyers were mainly men who had higher scores on the Exercise Addiction Inventory. One or more IPEDs classifiable as “potentially risky” were used by 66.3% of the sample. Users of “potentially risky IPEDs” were younger and primarily men. They showed higher scores both on the Exercise Addiction Inventory and Appearance Anxiety Inventory.ConclusionThis study profiled users of IPEDs when the most restrictive COVID-19 lockdown policies were implemented in all the participating countries. More targeted post-COVID 19 prevention strategies should be implemented according to the emerged socio-demographic and psychopathological traits and cross-cultural differences emerged. Longitudinal studies will also be needed to determine the long-term effect of the COVID-19 lockdown on IPEDs consumption.