Search Results (115)

Depression and anxiety are common comorbidities of stroke. Research has shown that about 30% of stroke survivors develop depression and about 20% develop anxiety. Stroke survivors with such adverse mental outcomes are often attributed to poorer health outcomes, such as higher mortality rates. The objective of this study is to use deep learning (DL) methods to predict the risk of a stroke survivor experiencing post-stroke depression and/or post-stroke anxiety, which is collectively known as post-stroke adverse mental outcomes (PSAMO). This study studied 179 patients with stroke, who were further classified into PSAMO versus no PSAMO group based on the results of validated depression and anxiety questionnaires, which are the industry’s gold standard. This study collected demographic and sociological data, quality of life scores, stroke-related information, medical and medication history, and comorbidities. In addition, sequential data such as daily lab results taken seven consecutive days after admission are also collected. The combination of using DL algorithms, such as multi-layer perceptron (MLP) and long short-term memory (LSTM), which can process complex patterns in the data, and the inclusion of new data types, such as sequential data, helped to improve model performance. Accurate prediction of PSAMO helps clinicians make early intervention care plans and potentially reduce the incidence of PSAMO. Full article

Background/Objectives: Diabetic foot infections (DFIs) are commonly associated with frequent hospitalizations, limb amputations, and premature death due to the profile of the bacteria infecting foot ulcers. DFIs are generally colonized by a polymicrobial net of bacteria that grows in biofilms, developing an increased antimicrobial resistance to multiple antibiotics. DFI treatment is a hurdle, and the need to develop new therapies that do not promote resistance is urgent. Therefore, the antibacterial efficacy of Nisin Z (antimicrobial peptide), a core–shell polycationic polyurea pharmadendrimer (PURE_G4OEI₄₈) (antimicrobial polymer), and amlodipine (antihypertensive drug) was evaluated against S. aureus and P. aeruginosa isolated from a DFI and previously characterized. Methods: The antibacterial activity was analyzed in vitro by determining the minimal inhibitory concentration (MIC) and in vivo in a Galleria mellonella model by assessing the larvae survival and health index. Results: The results indicate that Nisin Z exhibited antibacterial activity against S. aureus in vivo, allowing larvae full survival, and no antibacterial activity against P. aeruginosa. Nisin Z may have reduced the antibacterial effectiveness of both PURE_G4OEI₄₈ and amlodipine. PURE_G4OEI₄₈ significantly increased the survival of the larvae infected with P. aeruginosa, while amlodipine showed no activity against both bacteria in vivo. Conclusions: These findings suggest that both Nisin Z and PURE_G4OEI₄₈ could potentially be used individually as adjunct treatments for mild DFIs. However, further studies are needed to confirm these findings and assess the potential toxicity and efficacy of PURE_G4OEI₄₈ in more complex models. Full article

Cardiovascular disease is the worldwide leading cause of mortality among survivors of cancer due in part to the cardiotoxicity of anticancer therapies. This paper explores the progress in precision cardio-oncology, particularly in genetic testing and therapeutics, and its impact on cardiovascular diseases in clinical and laboratory settings. These advancements enable clinicians to better assess risk, diagnose conditions, and deliver personalised, cost-effective therapeutics. Through case studies of cancer-therapy-related cardiac dysfunction, clonal haematopoiesis of indeterminate potential, and polygenic risk scoring, we demonstrate the benefits of incorporating precision genomics in individualised care in cardio-oncology. Furthermore, leveraging real-world genomic data in clinical settings can advance our understanding of long noncoding RNAs and microRNAs, which play important regulatory roles in cardio-oncology. Additionally, employing human-induced pluripotent stem cells to stratify risk and guide prevention strategies represents a promising avenue for modelling precision cardio-oncology. While these advancements showcase the significant progress in genetic approaches, they also raise substantial ethical, legal, and societal concerns. Regulatory oversight of genetic and genomic technologies should therefore evolve suitably to keep up with rapid advancements in technology and analysis. Provider education is crucial for the appropriate use of new genetic and genomic applications, including on the existing protection available for patients regarding genetic information. This can provide confidence for diverse study groups to advance genetic studies looking to develop a comprehensive understanding and effective clinical applications for heterogeneous populations. In clinical settings, the implementation of genetic and genomic applications within electronic medical records can offer point-of-care clinical decision support, thus providing timely information to guide clinical management decisions. Full article

Radiolabelled fibroblast activation protein inhibitor (FAPI) tracers have the potential to overcome the limitations of 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) and improve the diagnosis and staging of hepato-pancreato-biliary (HPB) cancers. This study aims to compare the diagnostic performance of radiolabelled FAPI versus [¹⁸F]FDG PET imaging in HPB cancers. A systematic search of PubMed, Embase, Web of Science and Cochrane Library was performed to identify eligible studies on the diagnostic performance of FAPI PET for primary HPB tumours (hepatocellular carcinoma (HCC), pancreatic cancer (PC) and biliary tract cancer (BTC)) and for liver metastases of gastrointestinal origin. The diagnostic performance was defined as a combination of detection rate and semi-quantitative tracer uptake. A random-effects model was used to calculate the risk differences. In total, 28 studies were included. Histopathology was the reference standard for the primary tumour in 26 studies (93%). The detection rate of radiolabelled FAPI in comparison to [¹⁸F]FDG was significantly higher in HCC (0.33, 95% CI: 0.20–0.47 and 0.34, 95% CI: 0.23–0.45) and BTC (0.27, 95% CI: 0.11–0.43 and 0.28, 95% CI: 0.08–0.48), in the patient- and lesion-based analyses, respectively. In PC, no differences were observed. Radiolabelled FAPI outperformed [¹⁸F]FDG in the lesion-based detection of lymph node, liver and extra-hepatic metastases. In all HPB cancers, the mean SUVmax was significantly higher with radiolabelled FAPI compared to [¹⁸F]FDG. Molecular imaging with FAPI PET seems to have several benefits over [¹⁸F]FDG PET in HPB cancer diagnostics, with an overall higher tracer uptake, and higher detection rates in HCC and BTC. Full article

Background: Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) using the original 30 min protocol has shown limited benefits in patients with peritoneal metastasis of colorectal cancer (PMCRC), likely due to the short duration, which limits drug penetration into tumor nodules. Bevacizumab, an antiangiogenic antibody that modifies the tumor microenvironment, may improve drug delivery during HIPEC. This in silico study evaluates the availability of oxaliplatin within tumor nodules when HIPEC is performed after bevacizumab treatment. Methods: Using a computational fluid dynamics (CFD) model of HIPEC, the temperature and oxaliplatin distribution within the rat abdomen were calculated, followed by a model of drug transport within tumor nodules located at various sites in the peritoneum. The vascular normalization effect of the bevacizumab treatment was incorporated by adjusting the biophysical parameters of the tumor nodules. The effective penetration depth values, including the thermal enhancement ratio of cytotoxicity, were then compared between HIPEC alone and HIPEC combined with the bevacizumab treatment. Results: After bevacizumab treatments at doses of 0.5 mg/kg and 5 mg/kg, the oxaliplatin availability increased by up to 20% and 45% when HIPEC was performed during the vascular normalization phase, with the penetration depth increasing by 1.5-fold and 2.3-fold, respectively. Tumors with lower collagen densities and larger vascular pore sizes showed higher oxaliplatin enhancement after the combined treatment. Bevacizumab also enabled a reduction in the oxaliplatin dose (up to half at 5 mg/kg bevacizumab) while maintaining effective drug levels in the tumor nodules, potentially reducing systemic toxicity. Conclusions: These findings suggest that administering oxaliplatin-based HIPEC during bevacizumab-induced vascular normalization could significantly improve drug penetration and enhance treatment efficacy. Full article

Normal tissue reactions vary significantly among patients receiving the same radiation treatment regimen, reflecting the multifactorial etiology of late radiation toxicity. Predicting late radiation toxicity is crucial, as it aids in the initial decision-making process regarding the treatment modalities. For patients undergoing radiotherapy, anticipating late toxicity allows for planning adjustments to optimize individualized care. Various dosimetric parameters have been shown to influence the incidence of late toxicity, and the literature available on this topic is extensive. This narrative review examines patient-related determinants of late toxicity following external beam radiotherapy for pelvic tumors, with a focus on prostate and cervical cancer patients. In Part I, we address various methods for quantifying radiation toxicity, providing context for interpreting toxicity data. Part II examines the current insights into the clinical risk factors for late toxicity. While certain factors—such as previous abdominal surgery, smoking behavior, and severe acute toxicity—have consistently been reported, most of the others show inconsistent associations. In Part III, we explore the influence of genetic factors and discuss promising predictive assays. Single-nucleotide polymorphisms (SNPs) likely elevate the risk in specific combinations. Advances in artificial intelligence now allow for the identification of SNP patterns from large datasets, supporting the development of polygenic risk scores. These innovations hold promise for improving personalized treatment strategies and reducing the burden of late toxicity in cancer survivors. Full article

Background: Recent advancements in cancer treatment have shown the potential of immune checkpoint blockade (ICB) plus Viscum album L. therapy in improving survival rates for patients with advanced or metastatic non-small-cell lung cancer (NSCLC). The objective of this study was to investigate factors associated with improved survival in NSCLC patients treated with a combination of ICB and abnobaViscum^®. Methods: Patients with advanced or metastatic NSCLC from the accredited Network Oncology registry were included in this real-world data study adhering to ESMO-GROW criteria with ethics approval. Survival outcomes were compared between patients receiving ICB therapy alone versus those receiving combinational ICB plus abnobaViscum^® therapy using Kaplan–Meier and multivariable Cox proportional hazard analysis. Results: Among 300 patients (median age 68 years; male/female ratio 1.19), 222 received ICB alone (CTRL group) and 78 received combinational therapy (COMB group). Overall survival was significantly prolonged in the COMB group by 7 months compared to CTRL (13.8 months vs. 6.8 months, p = 0.005) with a survival rate of 16.5% in the COMB group vs. 8.0% in the CTRL group. In programmed death-ligand 1 positive (≥1%) patients treated with first-line ICB, the addition of abnobaViscum^® reduced the adjusted hazard of death by 75% (aHR: 0.25; 95%CI: 0.11–0.60, p = 0.02). Conclusions: The addition of abnobaViscum^® to ICB is significantly associated with improved survival in patients with advanced or metastatic NSCLC patients, irrespective of age, stage, Eastern cooperative oncology group status, surgery, or radiation. Potential mechanisms include immune modulation, reduced primary ICB resistance, and tumor microenvironment modifications. The findings warrant further validation in randomized controlled trials or registry-based randomized controlled trials. Trial registration: The study was registered (DRKS00013335). Full article

In this paper, we present a method to optimize the attainable moment set (AMS) to increase the control authority for electrical vertical take-off and landing vehicles (eVTOLs). As opposed to 3D AMSs for conventional airplanes, the hover control of eVTOLs requires vertical thrust produced by the powered lift system in addition to three moments. The limits of the moments and vertical thrust are coupled due to input saturation, and, as a result, the concept of the traditional AMS is extended to the 4D generalized moment set to account for this coupling effect. Given a required moment set (RMS) derived from system requirements, the optimization is formulated as a 4D convex polytope coverage problem, i.e., the AMS coverage over the RMS, such that the system’s available control authority is maximized to fulfill the prescribed requirements. The optimization accounts for not only nominal flight, but also for one critical engine inoperative situation. To test the method, it is applied to an eVTOL with eight rotors to optimize for the rotors’ orientation with respect to the body axis. The results indicate highly improved coverage of the RMS for both failure-free and one-engine-inoperative situations. Closed-loop simulation tests are performed for both optimal and non-optimal configurations to further validate the results. Full article

Equation discovery, also known as symbolic regression, is the field of machine learning that studies algorithms for discovering quantitative laws, expressed as closed-form equations or formulas, in collections of observed data. The latter is expected to come from measurements of physical systems and, therefore, noisy, moving the focus of equation discovery algorithms towards discovering approximate equations. These loosely match the noisy observed data, rendering them inappropriate for applications in mathematics. In this article, we introduce Diofantos, an algorithm for discovering equations in the ring of integers that exactly match the training data. Diofantos is based on a reformulation of the equation discovery task into the task of solving linear Diophantine equations. We empirically evaluate the performance of Diofantos on reconstructing known equations for more than 27,000 sequences from the online encyclopedia of integer sequences, OEIS. Diofantos successfully reconstructs more than 90% of these equations and clearly outperforms SINDy, a state-of-the-art method for discovering approximate equations, that achieves a reconstruction rate of less than 70%. Full article

Objectives: One of the behavioral problems strongly associated with emotional dysregulation (ED) in ASD is emotional outbursts (EOs) characterized by a pattern of challenging behavior that varies across individuals and across time. Cultural factors can modulate the expression of EOs. This study aimed to characterize the profile of emotional outbursts (EOs) in children with autism spectrum disorder (ASD) across various countries in Latin America and to identify clinical, emotional, and contextual factors that contribute to the onset and frequency of EOs within this diverse sample. Methods: A cross-sectional and cross-cultural study was conducted between 2023 and 2024 comprising samples from five countries in the Latin American Network for Autism-REAL: Argentina, Brazil, Chile, Uruguay, and the Dominican Republic. We studied 689 children with ASD (age x = 8.7 ± 2.6 years) using the Emotional Outburst Questionnaire (EOQ). Results: We identified different types of EO among children with ASD in our sample. The most frequent was the ‘behavioral indicators of emotion’ (52.0%) followed by ‘increased motor activity’ (28.3%), ‘non-speech vocalizations’, (27.6%), ‘mild verbal aggression’ (23.8%), and ‘avoidance’ (21.5%). Children in a bad mood or having a bad day or experiencing irritability were the most significant factors that increased the likelihood of EOs. Conclusions: Our results revealed that irritability is an important trigger for EOs and should not be disregarded or underestimated when monitoring the mental health of children with ASD. Full article

Aero-engines can be exposed to One Engine Inoperative (OEI) conditions during service, and the resulting overheating effect may significantly impact their structural integrity and flight safety. This paper focuses on the influence of overheating on the microstructural evolution and tensile properties of the GH4720Li alloy, a nickel-based polycrystalline superalloy commonly used in turbine disks. Based on the typical OEI operating conditions of a real aero-engine, a series of non-isothermal high-temperature tensile tests involving an OEI stage of 800 °C were conducted. The effects of OEI-induced overheating on the microstructure and tensile properties of the GH4720Li alloy were investigated. The results showed that, after OEI treatment, the primary γ′ phase in this alloy was partially dissolved. The GH4720Li superalloy also exhibited numerous microcracks at the grain boundaries, resulting in complex effects on its tensile properties. The alloy’s yield strength and ultimate tensile strength were slightly decreased, whereas its ductility decreased considerably. The OEI-induced embrittlement phenomenon was mainly caused by the non-uniform distribution of the tertiary γ′ phase within grains. The formation of microcracks nucleated at the interfaces between the primary γ′ precipitates and γ matrix phase was another key factor. Full article

Cloacal exstrophy is the most severe congenital anomaly of the exstrophy–epispadias complex and is characterized by gastrointestinal, genitourinary, neurospinal, and musculoskeletal malformations. Individualized surgical reconstruction by a multidisciplinary team is required for these complex patients. Not infrequently, patients need staged surgical procedures throughout childhood and adolescence. Following significant improvements in medical care and surgical reconstructive techniques, nearly all patients with cloacal exstrophy now survive, leading to an increased emphasis on quality of life. Increased attention is given to gender identity and the implications of reconstructive decisions. Long-term sequelae of cloacal exstrophy, including functional continence and sexual dysfunction, are recognized, and many patients require ongoing complex care into adulthood. Full article

Background: Owing to the association between dysfunctional maternal autonomic regulation and pregnancy complications, assessing non-invasive features reflecting autonomic activity—e.g., heart rate variability (HRV) and the morphology of the photoplethysmography (PPG) pulse wave—may aid in tracking maternal health. However, women with early pregnancy complications typically receive medication, such as corticosteroids, and the effect of corticosteroids on maternal HRV and PPG pulse wave morphology is not well-researched. Methods: We performed a prospective, observational study assessing the effect of betamethasone (a commonly used corticosteroid) on non-invasively assessed features of autonomic regulation. Sixty-one women with an indication for betamethasone were enrolled and wore a wrist-worn PPG device for at least four days, from which five-minute measurements were selected for analysis. A baseline measurement was selected either before betamethasone administration or sufficiently thereafter (i.e., three days after the last injection). Furthermore, measurements were selected 24, 48, and 72 h after betamethasone administration. HRV features in the time domain and frequency domain and describing heart rate (HR) complexity were calculated, along with PPG morphology features. These features were compared between the different days. Results: Maternal HR was significantly higher and HRV features linked to parasympathetic activity were significantly lower 24 h after betamethasone administration. Features linked to sympathetic activity remained stable. Furthermore, based on the PPG morphology features, betamethasone appears to have a vasoconstrictive effect. Conclusions: Our results suggest that administering betamethasone affects maternal autonomic regulation and cardiovasculature. Researchers assessing maternal HRV in complicated pregnancies should schedule measurements before or sufficiently after corticosteroid administration. Full article

Introduction: Prophylactic paracetamol for extremely low gestation age neonates (ELGAN, <27 weeks’ gestation) with symptomatic patent ductus arteriosus (sPDA) in high-income countries (HIC) reduces medical and surgical interventions. Its effectiveness in low-to-middle-income countries (LMIC) remains uncertain. This study assesses prophylactic paracetamol’s impact on sPDA interventions in ELGANs in an LMIC. Methods: This is a retrospective cohort study that compared a historical cohort of ELGANs that were treated with oral ibuprofen or intravenous paracetamol after diagnosis of sPDA (n = 104) with infants (n = 76) treated with prophylactic paracetamol (20 mg/kg loading, 7.5 mg/kg qid for 4 days), in a tertiary neonatal intensive care unit (NICU) in Vietnam. Oral ibuprofen or intravenous therapeutic paracetamol were administered if prophylactic paracetamol failed to close sPDA. Surgical ligation was conducted if targeted medical intervention failed, or the infant deteriorated from conditions attributable to sPDA. Results: In the historical cohort, 57 (55%) infants died within 7 days of life compared to 18 (24%) from the prophylactic cohort (p < 0.01). Of the survivors, 21 (45%) of the historical and 23 (39.7%) of the prophylactic cohort required surgical ligation (p = 0.6). Duration of hospitalization for survivors was lower in the prophylactic cohort (mean 74 vs. 97 days, p = 0.01). In the prophylactic cohort, 24 (41%) infants did not need further treatment while 34 (59%) required further treatment including ibuprofen and/or paracetamol 28 (48%) and surgical ligation 22 (38%). Conclusions: Prophylactic paracetamol for ELGAN in LMIC does not reduce the need for surgical ligation, sPDA rates, and other PDA-related morbidities in infants who survive beyond 7 days of age. It may reduce the risk of death and the duration of hospitalization but further study into the reasons behind this need to be determined with larger studies. Full article

Background: Baseline quality of life (bQL) has been shown to be a predictor of the clinical outcome of oncological patients. The primary objective of the present study was to examine the role of bQL as a treatment predictor in oncological patients. Methods: In this prospective study, all-stage cancer patients registered in the Network Oncology registry were enrolled, and their bQL at diagnosis was evaluated. Results: Five hundred and thirty-eight oncological patients were eligible (median age 64 years). We show that survival-predicting bQL variables such as pain, low physical functioning or financial burden at tumor diagnosis were linked to lower systemic treatment (p = 0.03), reduced surgery (p = 0.007) or reduced oncological treatment compliance (0.01), respectively. Lastly, female gender and older cancer patients exhibited a tempered bQL. Conclusion: Our study is one of the first to reveal that bQL at tumor diagnosis is significantly associated with the prediction of oncological treatment with distinctive age- and gender-related patterns. Our results emphasize the need to address the physical, psychosocial, and financial burden of cancer patients prior to their oncological treatment with respect to age and gender. The associations found here pave the way for early integration of patient-reported outcomes into oncological supportive concepts. Full article