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This study aims to develop a new data-driven methodology for identifying suitable influencers for a brand using data from social media. The increasing presence of such figures in these communication channels makes it challenging to select consistent and influential influencers for a specific audience. This paper introduces an innovative approach to defining these figures based on the analysis of relationships within the brand's network. Specifically, this methodology will be applied to the case study of a brand named “Anemonia”. The approach relies on the sequential application of various steps, including the use of tools such as Social Network Analysis (SNA) centrality, Sentiment Analysis (SA), and Analytical Hierarchical Process (AHP). Through the application of this methodology, the brand has been able to identify influencers consistent with its aesthetics and vision.

Abstract Background Liquid biopsies offer less burdensome sensitive disease monitoring. Bone marrow (BM) metastases, common in various cancers including neuroblastoma, is associated with poor outcomes. In pediatric high-risk neuroblastoma most patients initially respond to treatment, but in the majority the disease recurs with only 40% long-term survivors, stressing the need for more sensitive detection of disseminated disease during therapy. Methods To validate sensitive neuroblastoma mRNA RT-qPCR BM testing, we prospectively assessed serial BM samples from 345 international high‐risk neuroblastoma patients, treated in trials NB2004 (GPOH) or NBL2009 (DCOG), using PHOX2B, TH, DDC, CHRNA3, and GAP43 RT-qPCR mRNA markers and BM GD2-immunocytology. Association between BM-infiltration levels and event-free survival (EFS) and overall survival (OS) was estimated by using Cox regression models and Kaplan-Meier’s methodology. Results BM infiltration >10% by RT-qPCR at diagnosis was prognostic for survival (adjusted hazard ratio (HR) 1.82 [95%CI 1.25‐2.63] and 2.04 [1.33‐3.14] for EFS and OS, respectively). Any post-induction RT-qPCR positivity correlated with poor EFS and OS, with a HR of 2.10 [1.27-3.49] and 1.76 [1.01-3.08] and 5-years EFS of 26.6% [standard error 5.2%] versus 60.4% [6.7] and OS of 43.8% [5.9] versus 65.7% [6.6] for RT-qPCR-positive patients versus RT-qPCR-negative patients. In contrast, post-induction immunocytology positivity was not associated with EFS or OS (HR 1.22 [0.68-2.19] and 1.26 [0.54-2.42]). Conclusion This study validates the association of not clearing of BM metastases by sensitive RT-qPCR detection with very poor outcome. We therefore propose implementation of RT-qPCR for minimal residual disease testing in neuroblastoma to guide therapy.

Abstract Background Children and young adults needing surgery for a primary malignant bone tumour around the knee face a difficult, life-changing decision. A previous study showed that this population wants to be involved more in the decision-making process and that more involvement leads to less decisional stress and regret. Therefore, a well-designed and standardized decision-making process based on the principles of shared decision-making needs to be designed, implemented, and evaluated. Methods We developed a shared decision-making (SDM) model for this patient population, including an online decision aid (DA). This model has been implemented in the standard care of patients with a primary malignant bone tumour around the knee. Following implementation, we will analyse its effect on the decision-making process and the impact on patient experiences using questionnaires and interviews. Moreover, potential areas for improvement will be identified. Discussion Given the importance of involving patients and parents in surgical decision-making, particularly in life-changing surgery such as malignant bone tumour surgery, and given the lack of SDM models applicable for this purpose, we want to share our model with the international community, including our study protocol for evaluating and optimising the model. This study will generate valuable knowledge to facilitate the optimisation of current patient care for local treatment. The sharing of our implementation and study protocol can serve as an example for other centres interested in implementing SDM methods in an era characterized by more empowered patients and parents who desire autonomy and reliable and realistic information.

Objective: This study aims to assess the long-term safety and efficacy of adding pazopanib to neo-adjuvant radiotherapy followed by surgery in patients with high-risk non-metastatic soft tissue sarcoma of the trunk and extremities treated in the PASART-1 and PASART-2 trials, as well as to compare the PASART cohorts to a control cohort receiving standard treatment during the same time period from the Netherlands Cancer Registry (IKNL) to investigate if adding pazopanib improves Overall Survival (OS). Methods: Updated follow-up data on disease control, survival and long-term toxicities of the PASART-trials were extracted from electronic patient records. The effect of adding pazopanib to neo-adjuvant radiotherapy on OS was investigated by comparing the combined PASART cohorts to the IKNL cohort via direct comparison and exact matching analysis. Results: PASART-trials included 34 patients, IKNL cohort included 487 patients. After a median follow-up of 75.4 months (range: 30–131 months) the 1-year, 2-year and 5-year OS in the PASART-trials were 97% (95% confidence interval [CI]: 91.5–100), 85.3% (95% CI: 74.2–98.1), 79.3% (95% CI: 66.8–94.2), respectively. Matching resulted in 23 PASART and 89 IKNL patients. Adding pazopanib did not significantly improve OS when compared to standard treatment (IKNL) in a direct comparison (hazard ratio [HR]: 0.58; 95% CI: 0.30–1.13) or matched analysis (HR: 0.70; 95% CI: 0.29–1.73). Long-term toxicities, mainly fibrosis (n = 6) and edema (n = 2), were observed in 11 PASART patients and comparable to historical controls. Interpretation: The addition of pazopanib had tolerable long-term toxicity but did not improve OS when compared to a control cohort receiving standard treatment.

ALK is related to poor survival in neuroblastoma patients. We investigated the prognostic relevance of ALK mRNA expression and the relationship with ALK immunohistochemical expression, histological subtype and ALK aberrations. Whole transcriptome sequencing data were available from 54 patients. Overall survival (OS) and event-free survival (EFS) were estimated with Kaplan–Meier’s methodology. ALK protein expression was analyzed by immunohistochemistry. ALK aberrations were detected using whole exome sequencing, single nucleotide polymorphism array, next generation sequencing and/or fluorescence in situ hybridization. OS was 74.8% and EFS was 60%. ALK mRNA expression was not associated with OS (HR 1.127, 95% CI (0.812–1.854), p = 0.331) and adjusted EFS (HR 1.134, 95% CI (0.783–1.644), p = 0.505), but was associated with histological subtype (OR 1.914, 95% CI (1.083–3.382), p = 0.025) and ALK protein expression (negative versus weak: OR 2.829, 95% CI (1.290–6.204), p = 0.009) (negative versus moderate/strong: OR 2.934, 95% CI (0.889–9.679), p = 0.077). ALK mutated tumors had significantly higher ALK mRNA expression than non-mutated tumors (p < 0.001). MYCN-amplified neuroblastomas have higher MYCN mRNA expression (p ≤ 0.001), but not ALK mRNA expression (p = 0.553). ALK mRNA expression is higher in ALK mutated neuroblastomas and is associated with poorer differentiation degree and higher protein expression. ALK mRNA expression is not significantly associated with OS and EFS.

Current prediction models for patients with ostosarcoma are restricted to predictions from a single, static point in time, such as diagnosis or surgery. These approaches discard information which becomes available during follow-up and may have an impact on patient’s prognosis. This study aims at developing a dynamic prediction model providing 5-year overall survival (OS) predictions from different time points during follow-up. The developed model considers relevant baseline prognostic factors, accounting for where appropriate time-varying effects and time-varying intermediate events such as local recurrence (LR) and new metastatic disease (NM). A landmarking approach is applied to 1965 patients with high-grade resectable osteosarcoma from the EURAMOS-1 trial (NCT00143030). Results show that LR and NM negatively affected 5-year OS (HRs: 2.634, 95% CI 1.845–3.761; 8.558, 95% CI 7.367–9.942, respectively). Baseline factors with strong prognostic value (HRs > 2) included poor histological response (≥10% viable tumor), axial tumor location, and the presence of lung metastases. The effect of poor versus good histological response changed over time, becoming non-significant from 3.25 years post-surgery onwards. This time-varying effect, as well as the strong impact of disease-related time-varying variables, show the importance of including updated information collected during follow-up in the model to provide more accurate survival predictions.

This work reports the study of metal fragments from Roman pipes excavated from the archaeological site of Pompeii and currently preserved in the deposits of the National Archaeological Museum of Naples (MANN). The Roman pipe, called the tibia, is a reed wind musical instrument similar to the Greek aulos. It can be made of wood, bone, and/or metal. Materials consisting of metal Cu-based alloys were excavated from archaeological burial environments. This research aims to identify the composition of the alloys, characterize the corrosion patinas, and identify any ancient surface treatments on the fragments. Non-invasive and micro-invasive techniques were used to achieve this aim, i.e., optical microscopy, Raman spectroscopy, attenuated total reflectance Fourier-transform infrared spectrophotometry, scanning electron microscopy, and energy dispersive spectrometry. This research contributes to a deeper understanding of the materials and manufacturing techniques used for these instruments, as well as the degradation processes occurring over the centuries.

Infections lead to substantial morbidity during treatment of acute lymphoblastic leukemia (ALL) in which the adaptive immune system gets severely affected, leading to declining serum immunoglobulin levels. The aim of this trial was to investigate whether intravenous immunoglobulin (IVIG) prophylaxis in pediatric patients with ALL prevents admissions for fever. This randomized controlled trial was a subtrial of the national Dutch multicenter ALL study. Patients aged 1-19 years with medium risk (MR) ALL were randomized into two groups receiving either IVIG prophylaxis (0.7 g/kg IVIG given every three weeks, starting day 22 after diagnosis) or well defined standard of care (control group). Between October 2012 until March 2019, 91 (51%) patients were randomly assigned to IVIG prophylaxis and 86 (49%) to the control arm. In the IVIG prophylaxis group there were 206 admissions for fever versus 271 in the control group (p=0.011). IVIG prophylaxis was not associated with bacteremia. However, IVIG prophylaxis was associated with significantly less admissions for fever with negative blood cultures compared to the control group (N=113 versus 200, p

Introduction Treating older adults with chemotherapy remains a challenge, given their under-representation in clinical trials and the lack of robust treatment guidelines for this population. Moreover, older patients, especially those with frailty, have an increased risk of developing chemotherapy-related toxicity, resulting in a decreased quality of life (QoL), increased hospitalisations and high healthcare costs. Phase II trials have suggested that upfront dose reduction of chemotherapy can reduce toxicity rates while maintaining efficacy, leading to fewer treatment discontinuations and an improved QoL. The DOSAGE aims to show that upfront dose-reduced chemotherapy in older patients with metastatic colorectal cancer is non-inferior to full-dose treatment in terms of progression-free survival (PFS), with adaption of the treatment plan (monotherapy or doublet chemotherapy) based on expected risk of treatment toxicity.Methods and analysis The DOSAGE study is an investigator-initiated phase III, open-label, non-inferiority, randomised controlled trial in patients aged≥70 years with metastatic colorectal cancer eligible for palliative chemotherapy. Based on toxicity risk, assessed using the Geriatric 8 (G8) tool, patients will be stratified to either doublet chemotherapy (fluoropyrimidine with oxaliplatin) or fluoropyrimidine monotherapy. Patients classified as low risk will be randomised between a fluoropyrimidine plus oxaliplatin in either full-dose or with an upfront dose reduction of 25%. Patients classified as high risk will be randomised between fluoropyrimidine monotherapy in either full-dose or with an upfront dose reduction. In the dose-reduced arm, dose escalation after two cycles is allowed. The primary outcome is PFS. Secondary endpoints include grade≥3 toxicity, QoL, physical functioning, number of treatment cycles, dose reductions, hospital admissions, overall survival, cumulative received dosage and cost-effectiveness. Considering a median PFS of 8 months and non-inferiority margin of 8 weeks, we shall include 587 patients. The study will be enrolled in 36 Dutch Hospitals, with enrolment scheduled to start in July 2024. This study will provide new evidence regarding the effect of dose-reduced chemotherapy on survival and treatment outcomes, as well as the use of the G8 to choose between doublet chemotherapy or monotherapy. Results will contribute to a more individualised approach in older patients with metastatic colorectal cancer, potentially leading to improved QoL while maintaining survival benefits.Ethics and dissemination This trial has received ethical approval by the ethical committee Leiden Den Haag Delft (P24.018) and will be approved by the Institutional Ethical Committee of the participating institutions. The results will be disseminated in peer-reviewed scientific journals.Trial registration number NCT06275958.

Background and purpose: Developmental dysplasia (DDH) and Legg–Calvé–Perthes disease (LCPD) are common indications for total hip arthroplasty (THA) at a young age, and may be associated with increased revision risk. We aimed to investigate the 10-year cumulative aseptic cup revision and overall revision risk of THA, and investigated whether these are increased compared with THA for primary osteoarthritis (OA) in patients below 55 years. Methods: All THAs (2007–2019) in patients under the age of 55 for the indications OA, DDH, and LCPD were extracted from the Dutch Arthroplasty register. The 10-year cumulative incidences of aseptic cup failure and overall revision were assessed for the 3 groups, with death as a competing risk. Cox regression analysis was used. Results: 24,263 THAs were identified: 20,645 (85%) for OA, 3,032 (13%) for DDH, and 586 (2%) for LCPD. The 10-year cumulative revision risk for aseptic cup failure was 3.4% (95% confidence interval [CI] 3.0–3.8) for OA, 3.4% (CI 2.4–3.4) for DDH, and 1.7% (CI 0.2–3.1) for LCPD. The 10-year cumulative overall revision risk was 6.0% (CI 5.6–6.5) for OA, 6.0% (CI 4.9–7.2) for DDH, and 5.1% (2.7–7.5) for LCPD. The multivariable Cox regression analysis for aseptic cup failure yielded hazard ratios of 0.7 (0.5–1.2) for DDH, and 0.8 (0.3–2.1) for LCPD compared with OA. No statistically significant differences for overall revision were found. Conclusion: THA performed for DDH or LCDP in patients under the age of 55 was not associated with a statistically significant increased risk of aseptic cup revision or overall revision, compared with THA performed for primary OA in the same age group.

Mechanical properties may drastically change with temperature, which is crucial to characterize materials in environments as similar as possible to their desired application. This paper discusses a new furnace designed for thermomechanical experiments assisted by Digital Image Correlation (DIC) up to 900°C, with six transparent windows that allow for the visualization and lighting of the specimen. Its versatility is demonstrated in three different experimental configurations, namely, dilatometry, three-point bend experiment, and wedge splitting test. Applied forces and full-field data are used for robust calibration of parameters for numerical simulations.

The study concerned a diagnostic spectroscopic campaign carried out on the panel painting depicting the Coronation of the Virgin (first half of the 15th century) by the late-Gothic Italian painter Michele di Matteo. The main aims were the identification of the original painting materials and the characterization of the painter’s artistic technique. A combined approach based on non- and micro-invasive techniques was employed. Visible and ultraviolet-induced fluorescence photography was used to select the areas of interest for spectroscopic analyses; X-ray radiography assessed the state of conservation of the support, while X-ray fluorescence and external reflection Fourier transform infrared spectroscopies allowed the chemical identification of pigments, binders, and varnishes. Attenuated total reflection infrared spectroscopy, optical microscopy, and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy were used to visualize and characterize the materials in the pictorial layers. The results highlighted the presence of pigments, possibly applied with an egg binder, consistent with the period of the production of the painting, as well as modern pigments used during subsequent restorations: an imprimitura with lead white and a gypsum-based ground layer. Concerning the gilding, the guazzo technique was confirmed by identifying a red bolo substrate and gold leaf.

Eysenck’s biopsychological model of stress posits that the extraversion–introversion distinction is associated with different thresholds of arousal, which in turn moderate the stress response. Although higher thresholds of activation have been reported in the context of physiological stress induction, more contemporary research has resulted in mixed findings. The objective of the current study was to revisit Eysenck’s biopsychological model of stress by examining associations between the two personality dimensions (extraversion–introversion and neuroticism–stability) and stress reactivity in response to the Trier Social Stress Test. A total of 122 participants aged 18 to 80 years were recruited. Participants completed a battery of questionnaires, including a personality questionnaire, and were exposed to the TSST, during which salivary cortisol and galvanic skin responses (GSR) were recorded. People scoring higher on extraversion displayed heightened GSR relative to people scoring lower on extraversion. Furthermore, sex-based analyses suggest that this association was driven by females. No significant associations were found for cortisol or with respect to the neuroticism–stability dimension of personality. These findings highlight the need to take a more nuanced approach to investigating the association between personality and stress reactivity, highlighting the importance of the stress induction protocol and the stress-sensitive system under investigation.

The food industry constantly seeks new starter cultures with superior characteristics to enhance the sensory and overall quality of final products. Starting from a collection of Algerian dairy (goat and camel) lactic acid bacteria, this work focused on the exploration of the technological and probiotic potential of Weissella cibaria (VR81 and LVT1) and Lactiplantibacillus plantarum R12 strains isolated from raw camel milk and fermented milk, respectively. These bioactive strains were selected for their high performance among ten other LAB strains and were used as starter cultures to develop a novel and nutritionally enhanced dairy-like plant-based yogurt using quinoa (Chenopodium quinoa Willd) as a raw matrix. The strains were evaluated for their antagonistic effects against Listeria innocua, Listeria ivanovii, Staphylococcus aureus, Escherichia coli, Salmonella enterica, and Pseudomonas aeruginosa, resilience to acidic and osmotic challenges, and tolerance to gastrointestinal mimicking conditions (i.e., pepsin and bile salt). Their aggregation and adhesion profiles were also analyzed. Furthermore, L. plantarum and W. cibaria were tested in single and co-culture for the fermentation and biocontrol of quinoa. The strains exhibited probiotic properties, including a high potential for biocontrol applications, specifically against L. innocua and P. aeruginosa (20 mm diameter zone with the neutralized cell-free supernatant), which disappeared after protease treatment, suggesting that bioactive peptides might be responsible for the observed antimicrobial effect. Additionally, they demonstrated resilience to acidic (pH 2) and osmotic challenges (1M sucrose), tolerance to gastro-intestinal conditions, as well as good aggregation and adhesion profile. Furthermore, the strains were able to produce metabolites of interest, such as exopolysaccharide (yielding up to 4.7 mg/mL) and riboflavin, reaching considerable production levels of 2.5 mg/L upon roseoflavin selection. The application of W. cibaria and L. plantarum as primary starters (both in single and co-culture) for fermenting quinoa resulted in effective acidification of the matrix (ΔpH of 2.03 units) and high-quality beverage production. in vivo challenge tests against L. innocua showed the complete inhibition of this pathogen when L. plantarum was included in the starter, either alone or in combination with W. cibaria. Both species also inhibited Staphylococcus and filamentous fungi. Moreover, the co-culture of mutant strains of L. plantarum R12d and W. cibaria VR81d produced riboflavin levels of 175.41 µg/100 g in fermented quinoa, underscoring their potential as starters for the fermentation, biopreservation, and biofortification of quinoa while also displaying promising probiotic characteristics.

Abstract Background Dexamethasone is important in the treatment for pediatric acute lymphoblastic leukemia (ALL) but induces muscle atrophy with negative consequences for muscle mass, muscle strength, and functional abilities. The aim of this study was to establish the effect of a dexamethasone course on sarcopenia and physical frailty in children with ALL, and to explore prognostic factors. Methods Patients with ALL aged 3–18 years were included during maintenance therapy. Patients had a sarcopenia/frailty assessment on the first day of (T1) and on the day after (T2) a 5‐day dexamethasone course. Sarcopenia was defined as low muscle strength in combination with low muscle mass. Prefrailty and frailty were defined as having two or ≥three of the following components, respectively: low muscle mass, low muscle strength, fatigue, slow walking speed, and low physical activity. Chi‐squared and paired t‐tests were used to assess differences between T1 and T2. Logistic regression models were estimated to explore patient‐ and therapy‐related prognostic factors for frailty on T2. Results We included 105 patients, 61% were boys. Median age was 5.3 years (range: 3–18.8). At T1, sarcopenia, prefrailty, and frailty were observed in respectively 2.8%, 23.5%, and 4.2% of patients. At T2, the amount of patients with frailty had increased to 17.7% (p = 0.002), whereas the number of patients with sarcopenia and prefrailty remained similar. Higher ASMM (odds ratio [OR]: 0.49, 95% CI: 0.28–0.83), stronger handgrip strength (OR: 0.41, 95% CI: 0.22–0.77) and more physical activity minutes per day (OR: 0.98, 95% CI: 0.96–0.99) decreased the risk of frailty at T2. Slower walking performance (OR: 2, 95% CI: 1.2–3.39) increased the risk. Fatigue levels at T1 were not associated with frailty at T2. Conclusion Physical frailty increased strikingly after a 5‐days dexamethasone course in children with ALL. Children with poor physical state at start of the dexamethasone course were more likely to be frail after the course.

Surgeons are skilled at making complex decisions over invasive procedures that can save lives and alleviate pain and avoid complications in patients. The knowledge to make these decisions is accumulated over years of schooling and practice. Their experience is in turn shared with others, also via peer-reviewed articles, which get published in larger and larger amounts every year. In this work, we review the literature related to the use of Artificial Intelligence (AI) in surgery. We focus on what is currently available and what is likely to come in the near future in both clinical care and research. We show that AI has the potential to be a key tool to elevate the effectiveness of training and decision-making in surgery and the discovery of relevant and valid scientific knowledge in the surgical domain. We also address concerns about AI technology, including the inability for users to interpret algorithms as well as incorrect predictions. A better understanding of AI will allow surgeons to use new tools wisely for the benefit of their patients.