Innovative Agents Research Articles

EDI&S SO08 A novel approach to environmentally sustainable surgical theatre by rationalising surgical instrument set – a qualitative analysis

Abstract Background The surgical theatres are a major source of hospital waste generation. The NHS has set a net zero supply chain target by 2045. This aim is supported by the RCS intercollegiate green theatre checklist to reduce the environmental impact of operating theatres. One key area identified in this process, that will support the net-zero target is surgical instrument tray rationalisation. Laparoscopic cholecystectomy was identified as one of the most common surgical procedures performed in England. The purpose of this study was to demonstrate the impact of rationalising the number of surgical instruments, enabling surgeons to drive towards net zero surgery. Method Our Trust participated in this study, in collaboration with NHS England sustainable procurement team and the innovation agency. Total 58 cholecystectomies performed across two sites, Pinderfields and Dewsbury were included in this prospective audit undertaken from January – March 2023. The surgical tray checklists were used to record the actual instrument usage and noted the redundant and supplementary instruments. This data presented to a surgical advisory group, who agreed on routine instruments and proposed removal of redundant. A green pilot tray was approved and used for cholecystectomy. Qualitative questionnaire feedback was collected from surgeons and operation theatre staff from both sites. Results The instrument use matrix revealed almost 50% instruments from the previously used major tray were never used in any of the 58 cholecystectomy surgeries performed. Subsequently, based on the use matrix data, we switched from using major tray containing 84 instruments, to a reduced size tray containing 46 instruments including re-usable metal ports. Survey results revealed tray rationalisation led to easier and faster surgery preparation, improved efficiency and a reduction in waste, thereby reducing the cost to the Trust. It was also noted that having a smaller tray means less time to count instruments during the surgical pause. Conclusion The results of tray rationalisation are very positive and have demonstrated cost savings, carbon reduction and time saved preparing for surgery and the post-operative instrument count. This pilot study has shown that by making the surgical set smaller, savings have been achieved from a reduction of slots required per machine cycle for decontamination. Tray rationalisation goes some way towards the net goal of zero carbon surgery and delivering a sustainable future.

MTOR inhibitors potentially preserve fertility in female patients with haematopoietic malignancies: a narrative review.

Haematologic malignancies are considered among the more common adolescent and young adult (AYA) cancers. Many female AYA patients with haematopoietic malignancies face impaired fertility. Haematologic malignancies patients tend to be treated with more aggressive systemic chemotherapy than that of solid tumours. In adult women, treatment-related contraception causes age-related fertility loss. Graft-versus-host disease (GVHD) after allogeneic haematopoietic stem cell transplantation is associated with decreased fertility. Ovarian cryopreservation is often indicated for haematopoietic malignancies; however, follicle loss associated with ovarian cryopreservation and ovarian minimal residual disease, which result in the withdrawal of the transplantation, are important issues. These problems may not be fully addressed by conventional methods of fertility preservation, such as oocyte, embryo, and ovarian cryopreservation, leaving room for research into new treatment approaches, such as fertility preservation drugs. In recent years, preclinical studies have shown that mTOR inhibitors may preserve chemotherapy-induced follicular loss, may have follicle-preserving effects on follicle loss associated with cryopreservation and transplantation of ovarian tissue, may have fertility-preserving effects on aging-related infertility. Clinical studies have shown that mTOR inhibitors may have the potential for indirect fertility preservation by controlling GVHD, have a limited anti-tumor effect against haematopoietic malignancies. The purpose of this article is to outline the various issues faced by female survivors of haematopoietic malignancies and discuss the potential of mTOR inhibitors as a safe treatment option. Based on current research, mTOR inhibitors seem promising and innovative fertility preservation agents regarding preclinical conditions, and further study, including clinical trials, should be expected.

Green Hydrothermal Synthesis of Gallic Acid Carbon Dots: Characterization and Cytotoxic Effects on Colorectal Cancer Cell Line.

Colorectal cancer remains a leading cause of cancer-related deaths worldwide, necessitating the development of novel therapeutic approaches. Carbon dots (CDs) have emerged as promising nanoparticles for biomedical applications due to their unique properties. Gallic acid (GA), a known anticancer agent, is effective against various tumor types. This study explores the potential of gallic acid-derived carbon dots (GA-CDs) as an innovative anticancer agent against HCT-116 colorectal cancer cells, focusing on apoptosis signaling pathways. GA-CDs were synthesized using a one-pot hydrothermal method. Characterization was conducted using transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy, and ultraviolet-visible (UV-Vis) absorption spectroscopy. The cytotoxicity of GA and GA-CDs on HCT-116 cells was evaluated using the MTT assay at various concentrations over 24 and 48 hours. Cellular uptake was assessed via fluorescence microscopy, and apoptosis was analyzed using acridine orange/propidium iodide (AO/PI) staining. Total RNA extraction followed by complementary DNA (cDNA) synthesis via RT-PCR was performed, and real time-PCR (Q-PCR) was conducted to examine the expression of apoptosis-related genes Caspase-3, Bax, and Bcl-2. Characterization confirmed the successful synthesis of spherical GA-CDs. GA-CDs exhibited dose- and time-dependent cytotoxicity, with IC50 values of 88.55 µg/mL for GA-CDs and 192.2 µg/mL for GA after 24 hours. Fluorescence microscopy confirmed the efficient uptake of GA-CDs by HCT-116 cells. AO/PI staining showed a significant increase in apoptotic cell numbers after treatment with GA-CDs. Q-PCR analysis revealed overexpression of Caspase-3 and Bax genes in GA-CD-treated cells, though no significant changes were observed in the expression of Bcl-2 or the Bax/Bcl-2 ratio. GA-CDs demonstrated potent anticancer properties by inducing apoptosis and reducing cell viability in HCT-116 cells. These findings suggest the potential of GA-CDs as a novel therapeutic agent for colorectal cancer treatment, warranting further investigation into their mechanism of action and in vivo efficacy.

Design, Synthesis, and Molecular Docking of Quinazolines Bearing Caffeoyl Moiety for Targeting of PGK1/PKM2/STAT3 Signaling Pathway in the Human Breast Cancer.

PGK1 and PKM2 are glycolytic enzymes, and their expression is upregulated in cancer cells. STAT3 is a transcription factor implicated in breast cancer progression and chemoresistance. Researchers worldwide continue to explore how targeting genes might lead to more effective anti-breast cancer therapies. The present study aims to synthesize quinazolines containing caffeoyl moiety for developing innovative anticancer agents against the human breast cancer cell line (MCF-7). A new quinazoline 2 was synthesized by reacting caffeic acid with 5-amino-phenylpyrazole carboxylate 1 in the presence of PCl3. Compound 2 reacted with NH2NH2.H2O to produce compound 3 through cyclo-condensation. Apoptosis and necrosis as well as inhibition activity compounds 2 and 3 against PGK1, and PKM2 were evaluated. The effect of compounds 2 and 3 on the levels of GSH, GR, SOD, GPx, CAT, MDA, Bax, Bcl-2, caspase-3, P53 and VEGF levels as well as PGK1, PKM2 and STAT3 gene expression were estimated in MCF-7 tumor cells. The viability of MCF-7 cells was reduced to 22.42% and 45.86% after incubation with compounds 2 and 3 for 48 hours, respectively. The IC50 values for compounds 2 and 3 are 62.05 μg/mL and 16.73 μg/mL. Furthermore, compound 3 exhibited more significant apoptosis and necrosis than compound 2. IC50 values of compound 2 against PGK1, and PKM2 at interval concentration equals 1.04, and 0.32 μM/mL, respectively, after 210 minutes of incubation. Moreover, compound 3 were revealed strong inhibition of PGK1, and PKM2 with IC50 values equals 0.55 and 0.21 μg/mL, respectively after 210 minutes of incubation. Our results proved that the incubation of compounds 2 and 3 with MCF-7 cells increased the levels of apoptotic proteins, elevated MDA, Bax, caspase-3 and P53 levels, depleted GSH, GR, SOD, GPx, CAT, Bcl-2 levels and downregulated the levels of STAT3, PGK1, and PKM2 gene expression significantly. Our In-silico results proved that compound 2 showed a stronger estimated binding affinity with a ΔG of -7.2, -7.5, and - 7.9 kcal/mol., respectively towards PGK1, PKM2 and STAT3 proteins. Also, compound 3 exhibits a strong binding affinity with ΔG of -7.9, -8.5, and - 8.7 kcal/mol., towards PGK1, PKM2 and STAT3 proteins. The results show that compounds 2 and 3 induce apoptotic activity by blocking the PGK1- PKM2-STAT3 signaling pathway. The present investigation opens exciting possibilities for developing innovative new anticancer quinazolines bearing caffeoyl moiety.

Genetic Variants Affecting Iron Metabolism in Healthy Adults: A Systematic Review to Support Personalized Nutrition Strategies

Background/Objectives: Increased interest in personalized nutrition has led to a growing focus on exploring genetic variants and their impact on nutritional uptake (nutrigenomics). Nevertheless, no systematic review to date has compiled scientific evidence on genetic variants (such as single-nucleotide polymorphisms (SNPs)) affecting mineral metabolism in humans. This review aims to fill this gap and enable optimized personalized nutrition recommendations in health care. Methods: Cochrane, Embase and MEDLINE databases were systematically searched for English and German studies published between 2007 and 2023, focusing on genetic variants linked to nutrition. Studies on overweight, diseased, or underage individuals were excluded. Papers with verified findings were assessed for methodological quality using the Joanna Briggs Institute critical appraisal tool. Results: Twenty-one scientific papers on SNPs associated with mineral metabolism were included. The majority were observational studies (n = 19) conducted on Caucasian populations. Women outnumbered men (37.4%) women, 18.9% men, 43.7% sex not reported. All identified SNPs linked to minerals influenced iron parameters, with the TMPRSS6 gene showing the strongest correlation. Two HFE SNPs (rs1800562 and rs1799945) and one TF SNP (rs1799852) exhibited protective effects, while the other 11 SNPs were linked to increased risk of iron deficiency, suggesting potential benefits from iron supplementation for individuals with those genetic variants. Conclusions: This review provides comprehensive insights into the association between genetic variants and mineral metabolism, and the findings highlight the relevance of genetic makeup in optimizing health through nutritional interventions. The generalizability of the findings may be limited to Caucasians, warranting future research with diverse populations. This review was registered with the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) on 12 July 2022, under INPLASY202270068 and funded by the University Centre for Prevention and Sports Medicine at Balgrist University Hospital Zurich and the Swiss Innovation Agency Innosuisse, Switzerland.

Targeting Diabetes with Azole-derived Medicinal Agents.

Azoles have long been regarded as an ideal scaffold for the development of numerous innovative therapeutic agents as well as other incredibly adaptable and beneficial chemicals with prospective uses in a variety of fields, including materials, energetics (explosophores), and catalysis (azole organocatalytic arbitration). Azoles exhibit promising pharmacological activities, including antimicrobial, antidiabetic, antiviral, antidepressant, antihistaminic, antitumor, antioxidant, antiallergic, antihelmintic, and antihypertensive activity. According to a database analysis of U.S. FDAapproved medications, 59% of specific medications are connected to small molecules that have heterocycles having nitrogen atoms. The azole moiety has impressive electron abundance. Azoles promptly attach to various receptors as well as enzymes in the physiological environment via distinct specialized interactions, contributing to their anti-diabetic potential. This review encompasses the recent research progress on potent azole-derived antidiabetic agents that can be used as an alternative for the management of type-2 diabetes.

Zn(II) enhances the antimicrobial effect of chloroxine and structural analogues against drug-resistant ESKAPE pathogens in vitro

The emerging antibiotic-resistant bacteria, especially the “ESKAPE” pathogens, pose a continuous threat to global health. In this study, we explored metalloantibiotics as promising therapeutics and innovative antimicrobial agents. The role of metal in the antimicrobial activity of chloroxine (5,7-dichloro-8-hydroxyquinoline), as a metalloantibiotic, was investigated by minimal inhibit concentration (MIC) assay and a series of assays, including growth curve, time-killing, and UV–visible spectroscopy and PAR (4-(2-pyridylazo)-resorcinol) competition assays. Both chloroxine and its structural analogues exhibited increased antibacterial potency against Gram-positive bacteria compared to Gram-negative bacteria. The introduction of exogenous manganese or zinc ions significantly boosted chloroxine’s antibacterial efficacy against Gram-negative bacteria, including the notorious ESKAPE pathogens. However, the enhanced antibacterial activity induced by zinc ions could be negated in the presence of copper or ferrous iron ions, as well as changes in oxygen availability, highlighting the involvement of proton motive force, oxidative and antioxidative systems. Notably, chloroxine effectively inhibited the enzymatic activity of superoxide dismutase (SOD). In addition, chloroxine could reverse polymyxin and carbapenem resistance in E. coli in vitro. Therefore, these results suggested that chloroxine with zinc ions are promising therapeutics and antibiotics potentiator to combat multidrug-resistant ESKAPE pathogens

Lichen-associated Fungi Inhabiting from a Mangrove Ecosystem in Sri Lanka: A Novel Source of Antibacterial Agents

The global threat of antimicrobial resistance has spurred interest in discovering innovative antimicrobial agents from diverse sources. Amid the rise of new diseases, the quest for novel drug leads has intensified. This study explores the antibacterial potential of lichen-associated fungi in mangrove ecosystems, using NARA Regional Research Centre in Kalpitiya, Sri Lanka as the study site. Lichen-associated fungi were isolated from collected lichens and the antibacterial activities of the isolates were tested using two gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Bacillus cereus (ATCC 11778) and two gram-negative bacteria: Pseudomonas aeruginosa (ATCC 25853) and Escherichia coli (ATCC 25922). Putative fungal isolates were primarily screened using agar plug diffusion assay and ethyl acetate extracts of fungal isolates with marked activity were secondarily screened using the well diffusion assay in triplicate. Isolate LIF 0803 identified as Trichosporon faecale showed the most outstanding antibacterial activities as 2.58, 3.43, 4.2, 4.5 cm of zone diameter at 100 mg/mL, and 1.95, 3.08, 3.7, 4.3 cm of zone diameter at 50 mg/mL against P. aeruginosa, S. aureus, B. cereus, and E. coli respectively. All nine fungal isolates showed promising antibacterial activity against both gram-positive and negative bacteria. Therefore, this study showed that lichen-associated fungi in mangrove ecosystems have potent antibacterial activities. Hence, bioassay-guided fractionation of active compounds from lichen-associated fungi and structure elucidation are warranted.

Mitigating Effect of the Sea on Temperatures Along Mediterranean Coastal Areas: The Case of the Vine Territory of the Matera DOP in Basilicata (Italy)

This study aims to assess temperature variations caused by ongoing climate change in the Basilicata region, southern Italy—Ionian side of the Gulf of Taranto—on the territory of the Matera DOP vineyard. In particular, it aims to assess the influence of the sea on temperature trends, and particularly to its “mitigating effect” in the context of ongoing climate change. Temperature trends were analyzed using ERA5-Land data from 1981 to 2022 and data from weather stations of the Lucanian Agency for Development and Innovation in Agriculture from 2000 to 2023. Temperature trends were studied considering both the period of the vegetative-productive season of the vineyards and the whole year. The results of this study show that, for the historical period analyzed, the Matera DOP area showed a significant upward trend in temperatures, particularly in the inland areas. This increase, especially for minimum temperatures, is more evident at higher elevations than at lower elevations near the sea. Indeed, coastal areas benefit from the thermoregulatory effect of the Ionian Sea, which moderates temperature increases at lower elevations. It follows that the Matera DOP wine-growing areas, and particularly those furthest from the coastal strip, will have to adapt to harsh climatic conditions that will certainly affect the quality and typicality of the wines.

Phytochemical profiling and biological evaluation of the residues from industrial hemp (Cannabis sativa L.) inflorescences trimming: Focus on water extract

The study focused on investigating the phytochemical composition and bio-pharmacological properties of a water extract obtained from industrial hemp by-products, after trimming female inflorescences of Cannabis sativa L., cultivar Kompolti. The extract was found to be rich in phenolic compounds, particularly gallic acid, catechin, coumaric acid, ferulic acid, and benzoic acid. It also contained significant amounts of cannabidiolic acid and cannabigerolic acid as the main terpenophenols. To assess the biological potential of the extract, various ecotoxicological assays were conducted. The extract did not show significant phytotoxic effects on seedling germination in the allelopathic assay. In the brine shrimp (Artemia salina) lethality test, the LC50 value was 1.726 mg/mL, and in the Daphnia magna test, the extract showed no cardiotoxicity effects at the same concentration; thus, confirming its biocompatibility with these eukaryotic organisms. Additionally, the extract did not induce cytotoxicity in the murine C2C12 cell line till to the concentration of 1000 μg/mL. In isolated mouse prostate specimens, the extract (10–1000 μg/mL) also prevented LPS-induced gene expression of pro-inflammatory cytokines, namely tumor necrosis factor (TNF)α, interleukin (IL)-6, and IL-1β. Furthermore, the extract exhibited inhibitory effects on the growth of pathogenic bacterial, fungal, and dermatophyte species commonly associated with prostatitis. These results suggest that the residual powder from female inflorescence trimming can be considered an innovative plant material from the industrial hemp supply chain that deserves to be valorised in terms of recycling and upcycling; thus, reducing the environmental impact of the by-products and also opening the way for innovative health-promoting agents.

Proanthocyanidins protects 3-NPA-induced ovarian function decline by activating SESTRIN2-NRF2-mediated oxidative stress in mice

Abnormal apoptosis of ovarian cells caused by oxidative stress is an important cause of premature ovarian failure (POF). Previous studies revealed that proanthocyanidins (PCs) are powerful natural antioxidants that can safely prevent oxidative damage in humans. However, the protective effect and mechanism of PCs on ovarian function during the course of POF remain unknown. In this study, female mice were injected with 3-nitropropionic acid (3-NPA) to establish an ovarian oxidative stress model; at the same time, the mice were treated with PC via gavage. Thereafter, the expression of various apoptosis genes, hormones, and related molecules was assessed. Compared with those in the control group, the ovarian index, follicle count at all levels, expression of MVH, PCNA and BCL2, and estradiol (E2) and progesterone (P) levels were significantly lower in the POF group, but significant recovery was observed in terms of MVH and PCNA expression and E2 and P levels in the POF + PCs group. The apoptosis marker genes BAX and ROS were significantly increased in the POF group but were notably restored in the POF + PCs group. In addition, the expression of Sestrin2, an antiapoptotic protein, was significantly increased in the PCs treatment group, as were the upstream and downstream regulatory factors NRF2 and SOD2, and the indices of the Sestrin2 overexpression group were similar to those of the PCs treatment group. In summary, these findings suggest that PCs have potential as innovative therapeutic agents for preventing and treating POF by activating the protective SESTRIN2-NRF2 pathway against oxidative stress.

High Fischer ratio oligopeptides from Antarctic krill: Ameliorating function and mechanism to alcoholic liver injury through regulating AMPK/Nrf2/IκBα pathways

In this study, we devoted attention to the hepatoprotective functions of high Fischer ratio oligopeptides (HFOPs) from Antarctic krill (HFOPs-AK) on alcoholic liver injury of mice. The results indicated that HFOPs-AK significantly improved the pathological state of mice liver and kidney, reduced alanine aminotransferase (ALT) and aspartate transaminase (AST) activities, regulated lipid metabolism, and alleviated the burden on the liver. In addition, HFOPs-AK depicted anti-inflammatory and antioxidant effects by reducing tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) contents and increasing superoxide dismutase (SOD) and catalase (CAT) activities to reduce malondialdehyde (MDA) level. The hepatoprotective mechanism of HFOPs-AK was further revealed by quantitative reverse transcription PCR (RT-qPCR) analysis, and the results proved that HFOPs-AK had the ability to stimulate the adenosine 5‘-monophosphate-activated protein kinase (AMPK)/nuclearrespiratoty factor 2 (Nrf2)/inhibitor of NF-κB (IκBα) signaling pathways, thereby regulating the expression levels of downstream factors. The activation of these signaling pathways is essential for the regulation of lipid metabolism as well as anti-inflammatory and antioxidant functions. This finding offers a novel approach for the development of innovative hepatoprotective agents utilizing HFOPs-AK.

Exploring educational ecosystems: insights from the implementation of SchoolWeavers tool in Catalonia

ABSTRACT Education has undergone significant changes, leading to more complex and collaborative approaches that recognize schools as ecosystems where diverse stakeholders interact. Consequently, new processes and tools are needed to promote leadership within these ecosystems. To guide school leadership teams, we developed and piloted the online tool ‘SchoolWeavers’, which fosters relationships and collaboration across the ecosystem to improve learning and well-being. This study examines the initial outcomes of using SchoolWeavers as a school leadership strategy in five schools in Catalonia, Spain, by surveying 1,615 members of the ecosystem, including teachers, leaders, staff, families, students, and community professionals. The aim is to investigate school ecosystem dynamics through the domains addressed by the tool, such as empathy, trust, shared purpose, innovation, collaboration, equity, and personalized learning, identifying opportunities for improvement and ways to foster stronger educational ecosystems. Leadership teams showed the highest scores and positive perceptions, while students rated the domains lower. Community professionals had low participation, indicating weaker collaboration with the community. Trust and equity received the highest scores, whereas innovation and personalized learning were less valued. This study highlights the need for tools to strengthen educational ecosystems and identifies areas for improvement, particularly in innovation and student agency.

Characterization of a New Hsp110 Inhibitor as a Potential Antifungal

Fungal infections present a significant global health challenge, prompting ongoing research to discover innovative antifungal agents. The 110 kDa heat shock proteins (Hsp110s) are molecular chaperones essential for maintaining cellular protein homeostasis in eukaryotes. Fungal Hsp110s have emerged as a promising target for innovative antifungal strategies. Notably, 2H stands out as a promising candidate in the endeavor to target Hsp110s and combat fungal infections. Our study reveals that 2H exhibits broad-spectrum antifungal activity, effectively disrupting the in vitro chaperone activity of Hsp110 from Candida auris and inhibiting the growth of Cryptococcus neoformans. Pharmacokinetic analysis indicates that oral administration of 2H may offer enhanced efficacy compared to intravenous delivery, emphasizing the importance of optimizing the AUC/MIC ratio for advancing its clinical therapy.

A systematic review on the epidemiology and treatment options of multiple Myeloma in Asia

Multiple myeloma (MM) accounts for almost 15 % of all neoplastic malignancies around the globe. This systematic review intends to analyse data on the treatment and management of MM in selected regions in Asia to identify and prioritize areas that need attention. A comprehensive review of original articles, published in English from 2005 to 2022, derived from the PubMed/MEDLINE database was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. There were 98 studies from select regions of Asia (China, India, Taiwan, Hong Kong, and Singapore) on newly diagnosed MM and relapsed/refractory MM. This review evaluated the trends in disease outcomes with the gradual shift in treatment regimens from doublet to triplet. Additionally, this review also explored autologous stem cell transplant outcome and anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy in MM patients. This is the first systematic review attempting to collect data on the utility and comparison of innovative agents and modifications in treatment regimens in the context of the Asian population. This review established that the body of evidence for the management of MM was generally of poor quality and there is a need for more versatile studies in the region. Novel and innovative drug regimens may help in combating the illness but consorted efforts by researchers, industry partners, policymakers, and the government are key factors in the long-term survival of MM patients. In the current systematic review, the authors have tried to give a comprehensive account of the available treatments, trends in MM management and prognosis for MM in Asia.

Clinical impact of large genomic explorations at diagnosis in 198 pediatric solid tumors: a monocentric study aiming practical feasibility of precision oncology

IntroductionFaced to the growing development of collecting systematic molecular analyses in relapsed pediatric cancers to transform their targeted matched therapies, this study aimed to assess the clinical and therapeutic indications of systematic diagnostic genomic explorations performed in pediatric solid cancers to determine which type of screening and if it afford at relapse time an accurate targeted strategy.MethodsA total of 280 patients less than 22 years, referred at the University Hospitals of Strasbourg for a newly diagnosed solid tumor from January 2015 to December 2021, were prospectively genomically investigated since diagnosis. Using 7 different molecular tests going from single-gene methods (IHC, FISH, RT-PCR, Sanger sequencing, droplet digital PCR) to largescale analyses (Next-Generation sequencing, RNAsequencing and FoundationOne®CDx), we explored retrospectively the molecular findings in those pediatric solid tumors (except hematolymphoid cancers) to improve diagnosis, prognosis assessment and relapse therapeutics.ResultsOne hundred and ninety-eight patients (71%) underwent molecular biology (MB) at diagnosis. Thirty-eight different histologies were grouped into cerebral tumors (30%), sarcomas (26%, bone and soft tissues), various blastomas (27%), and other entities (17%). Over a median 40-month follow-up, the overall survival rate of patients was 85% and the relapse rate 28%. Of the 326 analyses carried out, 245 abnormalities (single nucleotide variations: 50%, fusions: 25%, copy number alteration: 20%) concerning 70 oncogenes were highlighted. The overall clinical impact rate was 84%. Broad-spectrum analyses had a higher therapeutic impact (57%) than the targeted analyses (28%). 75% of broad-spectrum tests found an actionable variant conducting 23% of patients to receive rapidly a matched targeted therapy since first relapse.ConclusionOur experience highlighted the clinical utility of molecular profiling of solid tumors as soon as at diagnosis in children to expect improving access to innovative agents at relapse.

Strategies for Perioperative Anticoagulant Reversal in Orthopedic Surgery: A Review.

The administration of anticoagulation therapy during major orthopedic surgeries is a clinical challenge due to the risk of thrombotic events and bleeding complications. This review aims to evaluate the current strategies and emerging developments in perioperative anticoagulation reversal. We conducted a literature review on the management of perioperative anticoagulant therapy, which included the current status of anticoagulant reversal agents, as well as personalized medicine, pharmacogenomics, artificial intelligence (AI), and novel drug delivery systems. The review indicates that reversal agents such as idarucizumab and andexanet alfa are crucial in managing bleeding associated with direct oral anticoagulants (DOACs). Personalized medicine, guided by pharmacogenomics, allows for tailored anticoagulation regimens. AI and machine learning (ML) algorithms can enhance the predictive capabilities for bleeding and thrombotic risks. Additionally, nanotechnology and biomarkers offer innovative approaches to drug delivery and personalized treatment. Integrating evidence-based guidelines with innovative reversal agents, personalized medicine, AI and nanotechnology opens a new era in perioperative anticoagulation management. These advancements can ensure patient safety, minimize bleeding risks, and improve surgical outcomes. Future research should focus on the clinical validation of these strategies to ensure their effectiveness across diverse patient populations.

Towards the Concept of Digital Grassroots Youth Innovation

In recent years, young people have acquired a more active role in different areas of public life, such as culture, politics and gender debates. However, the relevance of their role in innovation processes has remained largely undiscussed. Are young people, in particular those from working class backgrounds, a forgotten actor for innovation and technological change policies? This study aims to understand whether the youth population—who are widely connected to the Internet, who do not necessarily participate in formal educational spaces but are increasingly acquiring digital skills autonomously—can be considered as an agent of innovation. Specifically, this study aims to propose and define the concept of Digital Grassroots Youth Innovation. It is based on both empirical and theoretical sources. On the one hand, it relies on a compilation of experiences of innovative activities related to digital technologies led by young people in Argentina. On the other hand, it is supported by a theoretical discussion on (a) the different types of innovations and their subjects, (b) the specificities of the ‘marginal mass’ in informational capitalism and (c) the characterisation of the young population in Argentina as ‘NEET’ (not in education, employment or training). Finally, we ask about the role played by digital technologies and non-formal learning in these particular innovation processes.

Review of Gold Nanoparticles: Synthesis, Properties, Shapes, Cellular Uptake, Targeting, Release Mechanisms and Applications in Drug Delivery and Therapy

The remarkable versatility of gold nanoparticles (AuNPs) makes them innovative agents across various fields, including drug delivery, biosensing, catalysis, bioimaging, and vaccine development. This paper provides a detailed review of the important role of AuNPs in drug delivery and therapeutics. We begin by exploring traditional drug delivery systems (DDS), highlighting the role of nanoparticles in revolutionizing drug delivery techniques. We then describe the unique and intriguing properties of AuNPs that make them exceptional for drug delivery. Their shapes, functionalization, drug-loading bonds, targeting mechanisms, release mechanisms, therapeutic effects, and cellular uptake methods are discussed, along with relevant examples from the literature. Lastly, we present the drug delivery applications of AuNPs across various medical domains, including cancer, cardiovascular diseases, ocular diseases, and diabetes, with a focus on in vitro and in vivo cancer research.

Analysis of Local Innovation Productivity Agents Within Micro and Small Businesses in The Trade, Industry and Services Segments of The Federal District

Objective: To analyze the effects of the Local Innovation Agent – ​​Productivity program on the adoption of innovative practices and its impacts on the productivity of small businesses monitored in the Federal District in 2023. Theoretical Framework: Innovation is a central element for economic development, a strategy to make companies efficient and competitive in the markets in which they operate, through various types of changes in management and production processes, with results that impact productivity and commercial performance. Method: This research adopted a quantitative-exploratory approach based on the ALI Management System database, which uses the Innovation Radar tool to measure the impact on SMEs and bibliographic research focused on the culture of innovation in organizations. Results and Discussion: The results obtained revealed that the companies monitored during the program generally improved their scores in the dimensions analyzed. The results demonstrate that the commerce, industry and services sectors have different impacts and that innovation is still a topic that requires support and access for small businesses. Research Implications: The data collected in this study show the effectiveness of the Local Innovation Agent Program - Productivity in inducing the adoption of innovative practices by small businesses. It is a fact that by adopting measures to monitor entrepreneurs, it is possible to encourage reflection on the part of managers of these businesses so that they prioritize innovative measures that assist and result in business management capable of facing the adversities of market competition. Originality/Value: This study is valuable for analyzing the effectiveness of public innovation policies, with a focus on small businesses. It is clear that other studies are needed to compare results from different territories to better understand the needs of small businesses.