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Background: Hepatocellular carcinoma (HCC) poses a significant challenge for patients ineligible for surgical resection or liver transplantation. Local therapies like Stereotactic Body Radiotherapy (SBRT) are crucial for those with liver-limited disease. Insulin-like growth factor-1 (IGF-1) is a potential biomarker for liver function. This study evaluates IGF-1’s prognostic value in predicting survival outcomes in HCC patients undergoing SBRT. Methods: We analyzed 42 HCC patients treated with SBRT between May 2021 and January 2024, with IGF-1 levels measured within four weeks before SBRT. Patient demographics, tumor metrics, and clinical outcomes were examined. The prognostic significance of IGF-1 was assessed using Cox proportional hazards and ROC curve analysis to determine optimal IGF-1 cutoffs for survival prediction. A nomogram predicting 1-year and 2-year survival was constructed using a multivariate Cox model. Results: IGF-1 levels were significantly lower in patients with cirrhosis or sarcopenia. Median overall survival (OS) was 24 months, with a significant survival difference favoring patients with IGF-1 levels above 62.4 ng/ml (Hazard Ratio [HR]: 5.9, P = 0.0025). A multivariable Cox model including Child-Turcotte-Pugh (CTP) score, IGF-1, and tumor volume effectively predicted survival. IGF-1 and tumor volume significantly impacted OS (HR: 6.9 and 1.004, p = 0.014 and 0.0022, respectively). Integrating IGF-1 with CTP score improved predictive accuracy (c-index 0.66 to 0.75, p = 0.052).The nomogram, integrating IGF-1 with the CTP and tumour volume, exhibited robust predictive accuracy with an area under the curve (AUC) of 0.84 for 2-year survival. Conclusion: IGF-1 is a reliable biomarker for liver function and survival prediction in HCC patients undergoing SBRT. Higher IGF-1 levels indicate better prognosis. The developed nomogram, incorporating IGF-1, enhances clinical decision-making for SBRT management. Further validation in larger cohorts is needed.

This study aimed to learn about the impact of generative artificial intelligence (AI) on student creative thinking skills and subsequently provide instructors with information on how to guide the use of AI for creative growth within classroom instruction. This mixed methods study used qualitative and quantitative data collected through an AUT test conducted in a college-level creativity course. The authors measured flexibility, fluency, elaboration, and originality of the data to assess the impact of ChatGPT-3 on students’ divergent thinking. The results advocate for a careful approach in integrating AI into creative education. While AI has the potential to significantly support creative thinking, there are also negative impacts on creativity and creative confidence. The authors of this study believe that creativity is central to learning, developing students’ ability to respond to challenges and find solutions within any field; thus the results of this study can be applicable to any classroom faced with the impact and/or integrating the use of AI on idea generation.

Objective:Mammographic screening and management of breast cancer (BC) in elderly women are controversial and continue to be an important health problem. To investigate, through members of the Senologic International Society (SIS), the current global practices in BC in elderly women, highlighting topics of debate and suggesting perspectives.Materials and Methods:The questionnaire was sent to the SIS network and included 55 questions on definitions of an elderly woman, BC epidemiology, screening, clinical and pathological characteristics, therapeutic management in elderly women, onco-geriatric assessment and perspectives.Results:Twenty-eight respondents from 21 countries and six continents, representing a population of 2.86 billion, completed and submitted the survey. Most respondents considered women 70 years and older to be elderly. In most countries, BC was often diagnosed at an advanced stage compared to younger women, and age-related mortality was high. For this reason, participants recommended that personalized screening be continued in elderly women with a long life expectancy.In addition, this survey highlighted that geriatric frailty assessment tools and comprehensive geriatric evaluations needed to be used more and should be developed to avoid undertreatment. Similarly, multidisciplinary meetings dedicated to elderly women with BC should be encouraged to avoid under- and over-treatment and to increase their participation in clinical trials.Conclusion:Due to increased life expectancy, BC in elderly women will become a more important field in public health. Therefore, screening, personalized treatment, and comprehensive geriatric assessment should be the cornerstones of future practice to avoid the current excess of age-related mortality. This survey described, through members of the SIS, a global picture of current international practices in BC in elderly women.

Summary: Background: Optimal initial tacrolimus dosing and early exposure of tacrolimus after renal transplantation is not well studied. Methods: In this open-label, 6 months, multicenter, randomized controlled, non-inferiority study, we randomly assigned 432 renal allograft recipients to receive basiliximab induction, mycophenolate and steroids and either standard prolonged-release tacrolimus (trough levels: 7–9 ng/ml; Standard Care arm), or an initial 7-day fixed 5 mg/day dose of prolonged-release tacrolimus followed by lower tacrolimus predose levels (trough levels: 5–7 ng/ml; Slow & Low arm). The primary end point was the combined incidence rate of biopsy-proven acute rejections (BPAR; including borderline), graft failure, or death at 6 months with a non-inferiority margin of 12.5%. (EudraCT-Nr: 2013-001770-19. Findings: The combined primary endpoint in the Slow & Low arm was non-inferior compared to the Standard Care arm (22.1% versus 20.7%; difference: 1.4%, 90% CI −5.5% to 8.3%). The overall rate of BPAR including borderlines was similar (Slow & Low 17.4% versus Standard Care 16.6%). Safety parameters such as delayed graft function, kidney function, donor specific HLA-antibodies, infections, or post-transplantation diabetes mellitus did not differ. Interpretation: This is the first study to show that an initial fixed dose of 5 mg per day followed by lower tacrolimus exposure is non-inferior compared to standard tacrolimus therapy and equally efficient and safe within 6 months after renal transplantation. These data suggest that therapeutic drug monitoring for prolonged release tacrolimus can be abandoned until start of the second week after transplantation. Funding: Investigator-initiated trial, financial support by Astellas Pharma GmbH.

Donor proteinuria (DP) is a common but rarely evaluated aspect of today’s kidney transplant allocation process. While proteinuria after kidney transplantation is a risk factor for impaired graft function and survival, the long-term effects of DP in kidney transplantation have not yet been evaluated. Therefore, this study aims to investigate the impact of DP on the long-term outcome after kidney transplantation. A total of 587 patients were found to be eligible and were stratified into two groups: (1) those receiving a graft from a donor without proteinuria (DP−) and (2) those receiving a graft from a donor with proteinuria (DP+). At 36 months, there was no difference in the primary composite endpoint including graft loss and patient survival (log-rank test, p = 0.377). However, the analysis of DP+ subgroups showed a significant decrease in overall patient survival in the group with high DP (p = 0.017). DP did not adversely affect patient or graft survival over 36 months. Nevertheless, this work revealed a trend towards decreased overall survival of patients with severe proteinuria in the subgroup analysis. Therefore, the underlying results suggest caution in allocating kidneys from donors with high levels of proteinuria.

Background. Normothermic machine perfusion (NMP) is nowadays frequently utilized in liver transplantation. Despite commonly accepted viability assessment criteria, such as perfusate lactate and perfusate pH, there is a lack of predictive organ evaluation strategies to ensure graft viability. Hyperspectral imaging (HSI)—as an optical imaging modality increasingly applied in the biomedical field—might provide additional useful data regarding allograft viability and performance of liver grafts during NMP. Methods. Twenty-five deceased donor liver allografts were included in the study. During NMP, graft viability was assessed conventionally and by means of HSI. Images of liver parenchyma were acquired at 1, 2, and 4 h of NMP, and subsequently analyzed using a specialized HSI acquisition software to compute oxygen saturation, tissue hemoglobin index, near-infrared perfusion index, and tissue water index. To analyze the association between HSI parameters and perfusate lactate as well as perfusate pH, we performed simple linear regression analysis. Results. Perfusate lactate at 1, 2, and 4 h NMP was 1.5 [0.3–8.1], 0.9 [0.3–2.8], and 0.9 [0.1–2.2] mmol/L. Perfusate pH at 1, 2, and 4 h NMP was 7.329 [7.013–7.510], 7.318 [7.081–7.472], and 7.265 [6.967–7.462], respectively. Oxygen saturation predicted perfusate lactate at 1 and 2 h NMP (R2 = 0.1577, P = 0.0493; R2 = 0.1831, P = 0.0329; respectively). Tissue hemoglobin index predicted perfusate lactate at 1, 2, and 4 h NMP (R2 = 0.1916, P = 0.0286; R2 = 0.2900, P = 0.0055; R2 = 0.2453, P = 0.0139; respectively). Conclusions. HSI may serve as a noninvasive tool for viability assessment during NMP. Further evaluation and validation of HSI parameters are warranted in larger sample sizes.

Abstract Here, we present the case of an 81‐year‐old male patient, who was hospitalized for a severe form of COVID‐19. Transthoracic echocardiogram (TTE) performed 1 month after symptom onset was normal. Respiratory evolution was favourable, and the patient was discharged at Day 78. At 6 months, despite a good functional recovery, he presented pulmonary sequelae, and the TTE revealed a clear reduction of left ventricular ejection fraction (LVEF) and mild LV dilatation without cardiac symptoms. The cardiac magnetic resonance (CMR) using Lake Louise Criteria (LLC), T1 and T2 mapping showed focal infero‐basal LV wall oedema, elevated T1 and T2 myocardial relaxation times especially in basal inferior and infero‐lateral LV walls, and sub‐epicardial late gadolinium enhancement in those LV walls. The diagnosis of active myocarditis was raised especially based on TTE abnormalities and CMR LLC, T1 and T2 mapping. Currently, we are not aware of published reports of a 6 month post‐COVID‐19 active myocarditis.

Planning alternatives evaluation is often influenced by the evaluator’s background knowledge and preferences, and its objectivity is hard to guarantee. A comprehensive evaluation method combining Geographic Information System (GIS) with system analysis technology is proposed in this paper. Using a land use issue in America as an example, GIS was combined with Fuzzy Logic, and the Analytic Network Process (ANP) method was used to evaluate three planning alternatives. The evaluation value of each qualitative index was obtained by Fuzzy Comprehensive Evaluation, and the quantitative index value was calculated by GIS algorithms. A weighted hypermatrix of ANP network was constructed to reveal the overall relative importance weight of alternatives. The results indicate that, in this case study, the factor weight rankings that influenced the selection of the land use alternative are Ecological factors (above 40%), socioeconomic factors (30%), Physical and Chemical factors (10–17%), and cumulative related factors (10%). In the long run, choices of planning alternatives will greatly affect the natural environment, the physical and chemical environment, and the social economy. The results indicate planners have to pay attention to a wide range of both qualitative and quantitative factors as much as possible in land use decisions. This study illustrates how the GIS-ANP method combine qualitative and quantitative factors in planning for a comprehensive analysis, thus improving the objectivity of evaluating land use planning alternatives and determining the importance of influencing factors. Future work aims to optimize the evaluation index system of planning, and measure index values in a more precise way.

BackgroundDigitalization affects almost every aspect of modern daily life, including a growing number of health care services along with telemedicine applications. Fifth-generation (5G) mobile communication technology has the potential to meet the requirements for this digitalized future with high bandwidths (10 GB/s), low latency (

Analysis of convalescent plasma derived from individuals has shown that IgG3 has the most important role in binding to SARS-CoV-2 antigens; however, this has not yet been confirmed in large studies, and the link between binding and neutralization has not been confirmed. By analyzing plasma pools consisting of 247–567 individual convalescent donors, we demonstrated the binding of IgG3 and IgM to Spike-1 protein and the receptor-binding domain correlates strongly with viral neutralization in vitro. Furthermore, despite accounting for only approximately 12% of total immunoglobulin mass, collectively IgG3 and IgM account for approximately 80% of the total neutralization. This may have important implications for the development of potent therapies for COVID-19, as it indicates that hyperimmune globulins or convalescent plasma donations with high IgG3 concentrations may be a highly efficacious therapy.

Students' well-being, learning activities, and learning success are key student outcomes that can be affected by challenging times such as the COVID-19 pandemic. Thus, it is vital to investigate the role of important personal (resilience, self-efficacy) and social resources (support from family, friends, teachers, important other) for central student outcomes (life satisfaction as a vital aspect of well-being, learning activities, and learning success) alongside perception of the COVID-19 situation. While the pandemic affected all of society, adolescents as a group who face core developmental challenges were especially vulnerable towards being negatively affected by the pandemic. Thus, analyses are based on 220 adolescent students (60.9% female, 37.7% male, 1.4% diverse) in Germany who were 16.21 years old on average (SD = 0.88) at time of data collection in May 2021. Students filled out an online questionnaire on sociodemographics and variables of interest. Path models revealed that perceiving the COVID-19 pandemic as stressful was negatively related to life satisfaction ([beta] = -0.27). Furthermore, perceiving the COVID-19 pandemic as stressful was negatively related to students' self-efficacy ([beta] = -0.22) and positively to support from an important other ([beta] = 0.32). Moreover, several resources were mainly positively related to our central student outcomes ([beta] = 0.13-0.41), and perception of the COVID-19 situation mediated two of those relations. Results underscore the importance of students' self-efficacy, which was related to all student outcomes. Furthermore, the results and methodological issues can impact further research and practice.

The aim of our study was to evaluate hyperspectral imaging (HSI) as a rapid, non-ionizing technique for the assessment of organ quality and the prediction of delayed graft function (DGF) in kidney transplantation after static cold storage (SCS, n = 20), as well as hypothermic machine perfusion (HMP, n = 18). HSI assessment of the kidney parenchyma was performed during organ preservation and at 10 and 30 min after reperfusion using the TIVITA® Tissue System (Diaspective Vision GmbH, Am Salzhaff, Germany), calculating oxygen saturation (StO2), near-infrared perfusion index (NIR), tissue haemoglobin index (THI), and tissue water index (TWI). Recipient and donor characteristics were comparable between organ preservation groups. Cold ischemic time was significantly longer in the HMP group (14.1 h [3.6–23.1] vs. 8.7h [2.2–17.0], p = 0.002). The overall presence of DGF was comparable between groups (HMP group n = 10 (55.6%), SCS group n = 10 (50.0%)). Prediction of DGF was possible in SCS and HMP kidneys; StO2 at 10 (50.00 [17.75–76.25] vs. 63.17 [27.00–77.75]%, p = 0.0467) and 30 min (57.63 [18.25–78.25] vs. 65.38 [21.25–83.33]%, p = 0.0323) after reperfusion, as well as NIR at 10 (41.75 [1.0–58.00] vs. 48.63 [12.25–69.50], p = 0.0137) and 30 min (49.63 [8.50–66.75] vs. 55.80 [14.75–73.25], p = 0.0261) after reperfusion were significantly lower in DGF kidneys, independent of the organ preservation method. In conclusion, HSI is a reliable method for intraoperative assessment of renal microperfusion, applicable after organ preservation through SCS and HMP, and predicts the development of DGF.

The effectiveness of iron-based shape memory alloy (Fe-SMA, ‘memory-steel’) reinforcements has been proven in several studies and site applications. Due to the novelty of ribbed memory-steel reinforcement bars, limited research has been performed on their application in structural engineering, however. In this study, the bond behaviour of memory-steel bars in a near-surface-mounted configuration designed for prestressed strengthening of concrete structures was investigated. Memory-steel bars were installed on concrete blocks and activated by resistive heating before being subjected to pull-out load. The effects of heating and hence prestressing, bar ductility, bond length and rigidity of the fixation were studied based on obtained prestress, crack development, slip and bar strain. During activation of the bars, a longitudinal splitting crack with insignificant crack width occured. Two failure modes were observed during subsequent external loading, including tensile rupture of the bar when less ductile material was used, or bond failure when material with higher ductility was under investigation. Initial prestressing did not result in a reduced bond capacity. Based on the differential equation of bond behaviour, an analytical calculation procedure was developed that enables prediction of bond shear stress, slip, bar strain, pull-out load, as well as the use of a non-linear material behaviour.

Many existing concrete buildings worldwide require improvement in structural integrity. Previous research has proven the effectiveness of iron-based shape memory alloy (Fe-SMA or memory-steel) reinforcements for the prestressed strengthening of structures. The unique function of the material, i.e., the so-called shape memory effect, enables cost-effectiveness and presents simple ways to prestress defective building components. Ribbed memory-steel bars have only been available recently. This study aimed to investigate their performance in a novel strengthening technique, named near-surface mounted (NSM) method. Bond experiments with short bond lengths were performed to investigate the feasibility of this configuration and to identify the effects of several design parameters including: groove dimensions, bar diameter, bar material, cover depth, mortar strength, and concrete strength. The use of a digital image correlation system enabled detailed measurements of slips, crack width, and surface strain.An analytical procedure based on the differential equation of bond behaviour was developed, which enabled the calculation of slip, strain, bond shear stress, and load capacity. The results show that ribbed memory-steel bars can be used in an NSM configuration due to high bond capacity. The cover depth, substrate strength and elastic modulus had a significant effect on the failure mode and bond capacity.

AimsThe European Senior Program (ESP) aims to avoid waiting list competition between younger and elderly patients applying for renal transplantation. By listing patients ≥65 years on a separate waiting list and locally allocating of grafts ≥65 years exclusively to this cohort, waiting and cold ischemia times are predicted to be shortened, potentially resulting in improved kidney transplantation outcomes. This study compared a historic cohort of renal transplant recipients being simultaneously listed on the general and the ESP waiting lists with a collective exclusively listed on the ESP list in terms of surrogates of the transplantation outcome.MethodsTotal 151 eligible patients ≥ 65 years from Münster transplant Center, Germany, between 1999 and 2014 were included. Graft function, graft and patient survival were compared using surrogate markers of short- and long-term graft function. Patients were grouped according to their time of transplantation.ResultsRecipients and donors in the newESP (nESP) cohort were significantly older (69.6 ± 3.5 years vs 67.1 ± 2 years, pConclusionnESP recipients received significantly older grafts, but experienced significantly shorter time on dialysis. Cold ischemia times were comparable, but graft function in the nESP cohort was significantly better in the long term.

IntroductionEarly conversion to a CNI-free immunosuppression with SRL was associated with an improved 1- and 3- yr renal function as compared with a CsA-based regimen in the SMART-Trial. Mixed results were reported on the occurrence of donor specific antibodies under mTOR-Is. Here, we present long-term results of the SMART-Trial.Methods and materialsN = 71 from 6 centers (n = 38 SRL and n = 33 CsA) of the original SMART-Trial (ITT n = 140) were enrolled in this observational, non-interventional extension study to collect retrospectively and prospectively follow-up data for the interval since baseline. Primary objective was the development of dnDSA. Blood samples were collected on average 8.7 years after transplantation.ResultsDevelopment of dnDSA was not different (SRL 5/38, 13.2% vs. CsA 9/33, 27.3%; P = 0.097). GFR remained improved under SRL with 64.37 ml/min/1.73m2 vs. 53.19 ml/min/1.73m2 (p = 0.044). Patient survival did not differ between groups at 10 years. There was a trend towards a reduced graft failure rate (11.6% SRL vs. 23.9% CsA, p = 0.064) and less tumors under SRL (2.6% SRL vs. 15.2% CsA, p = 0.09).ConclusionsAn early conversion to SRL did not result in an increased incidence of dnDSA nor increased long-term risk for the recipient. Transplant function remains improved with benefits for the graft survival.

BackgroundSleep deprivation is a well-known risk factor for the performance of medical professionals. Solid organ transplantation (especially orthotopic liver transplantation (oLT)) appears to be vulnerable since it combines technically challenging operative procedures with an often unpredictable start time, frequently during the night. Aim of this study was to analyze whether night time oLT has an impact on one-year graft and patient survival.Material and methodsDeceased donor oLTs between 2006 and 2017 were retrospectively analyzed and stratified for recipients with a start time at day (8 a.m. and 6 p.m.) or at night (6 p.m. to 8 a.m.). We examined donor as well as recipient demographics and primary outcome measure was one-year patient and graft survival.Results350 oLTs were conducted in the study period, 154 (44%) during daytime and 196 (56%) during nighttime. Donor and recipient variables were comparable. One-year patient survival (daytime 75.3% vs nighttime 76.5%, p = 0.85) as well as graft survival (daytime 69.5% vs nighttime 73.5%, p = 0.46) were similar between the two groups. Frequencies of reoperation (daytime 53.2% vs nighttime 55.1%, p = 0.74) were also not significantly different.ConclusionOur retrospective single center data derived from a German transplant center within the Eurotransplant region provides evidence that oLT is a safe procedure irrespective of the starting time. Our data demonstrate that compared to daytime surgery nighttime liver transplantation is not associated with a greater risk of surgical complications. In addition, one-year graft and patient survival do not display inferior results in patients undergoing nighttime transplantation.

BACKGROUND:The weekend effect describes a phenomenon whereby patients admitted to hospitals on weekends are at higher risk of complications compared to those admitted during weekdays. However, if a weekend effect exists in orthotopic liver transplantation (oLT). METHODS:We analyzed oLT between 2006 and 2016 and stratified patients into weekday (Monday to Friday) and weekend (Saturday, Sunday) groups. Primary outcome measures were one-year patient and graft survival. RESULTS:364 deceased donor livers were transplanted into 329 patients with 246 weekday (74.77%) and 83 weekend (25.23%) patients. Potential confounders (e.g. age, ischemia time, MELD score) were comparable. One-year patient and graft survival were similar. Frequencies of rejections, primary-non function or re-transplantation were not different. The day of transplantation was not associated with one-year patient and graft survival in multivariate analysis. CONCLUSIONS:We provide the first data for the Eurotransplant region on oLT stratified for weekend and weekday procedures and our findings suggest there was no weekend effect on oLT. While we hypothesize that the absent weekend effect is due to standardized transplant procedures and specialized multidisciplinary transplant teams, our results are encouraging showing oLT is a safe and successful procedure, independent from the day of the week.

Current cold storage organ preservation technique fails to preserve marginal donor grafts sufficiently. Evidence from large animal experiments suggests superiority of normothermic machine preservation of liver allografts. Long-term organ preservation using normothermic perfusion might not only allow organ viability assessment before transplantation, but also provide the means for further organ modifications under physiologic conditions. Previous research has shown that porcine livers can be transplanted successfully after normothermic preservation of 20 hours. In the present study we investigate whether similar methodology is capable of further extending the safe limit to 48 hours. In this study, livers from White Landrace pigs were preserved by normothermic, oxygenated sanguineous perfusion. After a 48-hour period of preservation, livers were transplanted into recipient pigs and followed for 5 days. Outcome parameters measured included markers of synthetic and metabolic liver function as well as hepatocellular injury and blood gas analysis during perfusion and follow-up. Histological assessment of morphological liver integrity was performed. All livers showed sustained bile production and metabolic activity throughout the preservation period. Low levels of hepatocellular damage were found. Following transplantation all liver grafts revealed excellent graft function and death-censored graft survival was 100%. Porcine livers were transplanted successfully following 48 hours normothermic machine preservation.

Cobalamin (vitamin B12) deficiency is particularly common in the elderly (>65 years of age) but is often unrecognized because its clinical manifestations are subtle; however, they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. In the elderly, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. Food-cobalamin malabsorption syndrome is a disorder characterized by the inability to release cobalamin from food or its binding proteins. This syndrome is usually caused by atrophic gastritis, related or unrelated to Helicobacter pylori infection, and long-term ingestion of antacids and biguanides. Management of cobalamin deficiency with cobalamin injections is currently well documented but new routes of cobalamin administration (oral and nasal) are being studied, especially oral cobalamin therapy for food-cobalamin malabsorption.

The degradation pathways for polymeric materials and coatings under the influence of light and oxygen are presented and the consequent need for light-protecting agents (light stabilisers) is discussed. The mechanisms of action of hindered amine light stabilisers and certain UV-absorbers are explained. The use of light stabilisers in photographic-, automotive- and wood-coatings as well as cosmetic applications is described.