Miracle-dz/UniFAR-FTUs huggingface dataset:
The Impact of Cell-Free DNA Analysis on the Management of Retinoblastoma

Simple Summary Retinoblastoma is a childhood eye cancer caused almost entirely by defects in a gene known as RB1. Other genetic changes within the tumour are also thought to affect the progression of disease. Until recently, tumour DNA could only be analysed if the eye was removed as part of patient treatment. However, recent research has shown that the analysis of a particular type of DNA, known as cell-free DNA, within the eye fluid or blood of patients, can be used to detect changes in the RB1 gene or other parts of the genome within a retinoblastoma tumour. The analysis of cell-free DNA in the blood of pregnant women can also be used to detect whether the unborn baby will be affected with retinoblastoma. In this review, we summarise these studies and discuss the potential impact of cell-free DNA analysis on retinoblastoma patient management in the future. Abstract Retinoblastoma is a childhood eye cancer, mainly caused by mutations in the RB1 gene, which can be somatic or constitutional. Unlike many other cancers, tumour biopsies are not performed due to the risk of tumour dissemination. As a result, until recently, somatic genetic analysis was only possible if an affected eye was removed as part of a treatment. Several recent proof of principle studies have demonstrated that the analysis of tumour-derived cell-free DNA, either obtained from ocular fluid or blood plasma, has the potential to advance the diagnosis and influence the prognosis of retinoblastoma patients. It has been shown that a confirmed diagnosis is possible in retinoblastoma patients undergoing conservative treatment. In vivo genetic analysis of retinoblastoma tumours is also now possible, allowing the potential identification of secondary genetic events as prognostic biomarkers. In addition, noninvasive prenatal diagnosis in children at risk of inheriting retinoblastoma has been developed. Here, we review the current literature and discuss the potential impact of cell-free DNA analysis on both the diagnosis and treatment of retinoblastoma patients and their families.
Gait Stability Measurement by Using Average Entropy

Gait stability has been measured by using many entropy-based methods. However, the relation between the entropy values and gait stability is worth further investigation. A research reported that average entropy (AE), a measure of disorder, could measure the static standing postural stability better than multiscale entropy and entropy of entropy (EoE), two measures of complexity. This study tested the validity of AE in gait stability measurement from the viewpoint of the disorder. For comparison, another five disorders, the EoE, and two traditional metrics methods were, respectively, used to measure the degrees of disorder and complexity of 10 step interval (SPI) and 79 stride interval (SI) time series, individually. As a result, every one of the 10 participants exhibited a relatively high AE value of the SPI when walking with eyes closed and a relatively low AE value when walking with eyes open. Most of the AE values of the SI of the 53 diseased subjects were greater than those of the 26 healthy subjects. A maximal overall accuracy of AE in differentiating the healthy from the diseased was 91.1%. Similar features also exists on those 5 disorder measurements but do not exist on the EoE values. Nevertheless, the EoE versus AE plot of the SI also exhibits an inverted U relation, consistent with the hypothesis for physiologic signals.
Discovery of Volatile Biomarkers for Bladder Cancer Detection and Staging through Urine Metabolomics

Timely diagnosis is crucial to improve the long-term survival of bladder cancer (BC) patients. The discovery of new BC biomarkers based in urine analysis is very attractive because this biofluid is in direct contact with the inner bladder layer, in which most of the neoplasms develop, and is non-invasively collected. Hence, this work aimed to unveil alterations in the urinary volatile profile of patients diagnosed with BC compared with cancer-free individuals, as well as differences among patients diagnosed at different tumor stages, to identify candidate biomarkers for non-invasive BC diagnosis and staging. Urine analysis was performed by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS). The results unveiled that BC patients have a distinct urinary volatile profile characterized by higher levels of several alkanes and aromatic compounds, and lower levels of aldehydes, ketones and monoterpenes. Seventeen significantly altered volatiles were used to evaluate the performance for overall BC detection, disclosing 70% sensitivity, 89% specificity and 80% accuracy. Moreover, distinct urinary volatile profiles were found among patients diagnosed at different tumor stages (Ta/Tis, T1 and ≥T2). This work identified distinct urinary volatile signatures of BC patients with potential for non-invasive detection and staging of bladder cancer.
Deposition of oral streptococci and polystyrene latices onto glass in a parallel plate flow cell

Deposition of oral bacteria onto glass from a potassium phosphate buffered suspension has been studied in a parallel plate flow cell. Three bacterial strains with known surface free energies and zeta potentials, and two Strains (S. salivarius HB and S. salivarius HB‐C12) having well‐defined surface appendages have been employed. Polystyrene latices were included to provide a comparison with inert particles. Initial deposition rates of the various bacteria ranged from 0–1—2·9 × 103 particles cm “"2 sec”; ‘. The initial deposition rates have been related to an approximate theory of convective diffusion in which electrostatic interactions are omitted. A theory describing the influence of particle desorption and blocking on the deposition rate has been tested for its applicability to bacterial deposition at later stages. From the results it is concluded that a simple convective diffusion theory overestimates the experimental results, due to an increase in hydrodynamic friction of particles closely approaching.
Present and Future Perspectives on Therapeutic Options for Carbapenemase-Producing Enterobacterales Infections

Carbapenem-resistant Enterobacterales (CRE) are included in the list of the most threatening antibiotic resistance microorganisms, being responsible for often insurmountable therapeutic issues, especially in hospitalized patients and immunocompromised individuals and patients in intensive care units. The enzymatic resistance to carbapenems is encoded by different β-lactamases belonging to A, B or D Ambler class. Besides compromising the activity of last-resort antibiotics, CRE have spread from the clinical to the environmental sectors, in all geographic regions. The purpose of this review is to present present and future perspectives on CRE-associated infections treatment.
Skin Wound-Healing Potential of Polysaccharides from Medicinal Mushroom Auricularia auricula-judae (Bull.)

Auricularia auricula-judae, a nutrient-rich mushroom used in traditional medicine, is a macrofungi that exhibits various biological properties. In this study, we have reported on the mechanisms that promote the wound-healing effects of a water-soluble polysaccharide-rich extract obtained from A. auricula-judae (AAP). AAP contained high amounts of polysaccharides (349.83 ± 5.00 mg/g extract) with a molecular weight of 158 kDa. The main sugar composition of AAP includes mannose, galactose, and glucose. AAP displayed antioxidant activity in vitro and was able to abort UVB-induced intracellular ROS production in human fibroblasts in cellulo. AAP significantly promoted both fibroblast and keratinocyte proliferation, migration, and invasion, along with augmentation of the wound-healing process by increasing collagen synthesis and decreasing E-cadherin expression (All p < 0.05). Specifically, the AAP significantly accelerated the wound closure in a mice skin wound-healing model on day 9 (2.5%AAP, p = 0.031 vs. control) and day 12 (1% and 2.5%AAP with p = 0.009 and p < 0.001 vs. control, respectively). Overall, our results indicate that the wound-healing activities of AAP can be applied in an AAP-based product for wound management.
The Effect of Vasopressin Antagonists on Maternal-Separation-Induced Ultrasonic Vocalization and Stress-Hormone Level Increase during the Early Postnatal Period

In adults, vasopressin exerts an anxiogenic effect, but less is known about the perinatal period. As a sign of distress, rat pups emit ultrasonic vocalizations when they are separated from their mothers, known as maternal separation-induced ultrasonic vocalization (MS-USV). Previously, reduced MS-USV was reported in 7–8-day-old genetically vasopressin-deficient Brattleboro rats. Here, we aimed to examine the contributing vasopressin receptor (VR) subtypes using Wistar pups. MS-USV was recorded for 10 min, 30 min after vasopressin (V) 1aR, V1bR or V2R antagonist treatment (SR49059, SSR149415, SR121463B; 3, 10 and 30 mg/kg, intraperitoneal). Sedation was studied by the righting reflex and negative geotaxis, and finally, the stress hormone levels were measured by radioimmunoassay. The vasopressin-deficient pups showed decreased MS-USV and adrenocorticotropin levels even after a saline injection, with unchanged corticosterone levels. Thirty mg/kg of V1aR-antagonist increased the corticosterone levels. All V1bR antagonist doses decreased the MS-USV and adrenocorticotropin, while 10 + 10 mg/kg of V1aR and V1bR antagonists decreased MS-USV without influencing the stress hormones. Three mg/kg of V2R antagonist enhanced MS-USV, while 30 mg/kg increased the stress hormone levels. We confirmed that vasopressin deficiency already caused anxiolytic effects in pups. V1bRs are the most important player in connection with their adrenocorticotropin (ACTH)-regulatory role, but a combination of V1aR and V1bR antagonists might be also beneficial through other mechanisms, reducing the possibility of side effects. In contrast, antagonizing the V2Rs may be stressful due to an induction of imbalance in saltwater homeostasis.
Synthetic Biomimetic Polymethacrylates: Promising Platform for the Design of Anti-Cyanobacterial and Anti-Algal Agents

Extensive, uncontrolled growth of algae and cyanobacteria is an environmental, public health, economic, and technical issue in managing natural and engineered water systems. Synthetic biomimetic polymers have been almost exclusively considered antimicrobial alternatives to conventional antibiotics to treat human bacterial infections. Very little is known about their applicability in an aquatic environment. Here, we introduce synthetic biomimetic polymethacrylates (SBPs) as a cost-effective and chemically facile, flexible platform for designing a new type of agent suitable for controlling and mitigating photosynthetic microorganisms. Since SBPs are cationic and membranolytic in heterotrophic bacteria, we hypothesized they could also interact with negatively charged cyanobacterial or algal cell walls and membranes. We demonstrated that SBPs inhibited the growth of aquatic photosynthetic organisms of concern, i.e., cyanobacteria (Microcystis aeruginosa and Synechococcus elongatus) and green algae (Chlamydomonas reinhardtii and Desmodesmus quadricauda), with 50% effective growth-inhibiting concentrations ranging between 95 nM and 6.5 μM. Additionally, SBPs exhibited algicidal effects on C. reinhardtii and cyanocidal effects on picocyanobacterium S. elongatus and microcystin-producing cyanobacterium M. aeruginosa. SBP copolymers, particularly those with moderate hydrophobic content, induced more potent cyanostatic and cyanocidal effects than homopolymers. Thus, biomimetic polymers are a promising platform for the design of anti-cyanobacterial and anti-algal agents for water treatment.
The Economic Costs of Childhood Disability: A Literature Review

Background: This literature review investigates the economic costs of childhood disability analysing methodologies used and summarizing the burden worldwide comparing developed and developing countries. Methods: Four electronic databases were searched. Studies were categorised according to country, perspective, methods of costing, disability category, and time horizon. Annual costs were converted to 2019 current US dollars then compared to the country’s per capita current health expenditure (CHE) and gross domestic product (GDP). Results: Of 2468 references identified, 20 were included in the review. Annual burden of childhood disability ranged ≈$450–69,500 worldwide. Childhood disability imposes a heavy economic burden on families, health systems, and societies. The reason for the wide range of costs is the variability in perspective, costs included, methods, and disability type. Conclusion: The annual societal costs for one disabled child could be up to the country’s GDP per capita. The burden is heavier on households in developing countries as most of the costs are paid out-of-pocket leading to impoverishment of the whole family. Efforts should be directed to avoid preventable childhood disabilities and to support disabled children and their households to make them more independent and increase their productivity. More studies from developing countries are needed.
Simulating Expansion of the Intracranial Space to Accommodate Brain Swelling after Decompressive Craniectomy: Volumetric Quantification in a 3D CAD Skull Model with Contour Elevation

Background: Decompressive craniectomy (DC) can be used to augment intracranial space and halt brainstem compromise. However, a widely adopted recommendation for optimal surgical extent of the DC procedure is lacking. In the current study, we utilized three-dimensional (3D) computer-assisted design (CAD) skull models with defect contour elevation for quantitative assessment. Methods: DC was performed for 15 consecutive patients, and 3D CAD models of defective skulls with contour elevations (0–50 mm) were reconstructed using commercial software. Quantitative assessments were conducted in these CAD subjects to analyze the effects of volumetric augmentation when elevating the length of the contour and the skull defect size. The final positive results were mathematically verified using a computerized system for numerical integration with the rectangle method. Results: Defect areas of the skull CAD models ranged from 55.7–168.8 cm2, with a mean of 132.3 ± 29.7 cm2. As the contour was elevated outward for 6 mm or above, statistical significance was detected in the volume and the volume-increasing rate, when compared to the results obtained from the regular CAD model. The volume and the volume-increasing rate increased by 3.665 cm3, 0.285% (p < 0.001) per 1 mm of contour elevation), and 0.034% (p < 0.001) per 1 cm2 of increase of defect area, respectively. Moreover, a 1 mm elevation of the contour in Groups 2 (defect area 125–150 cm2) and 3 (defect area >150 cm2, as a proxy for an extremely large skull defect) was shown to augment the volume and the volume-increasing rate by 1.553 cm3, 0.101% (p < 0.001) and 1.126 cm3, 0.072% (p < 0.001), respectively, when compared to those in Group 1 (defect area <125 cm2). The volumetric augmentation achieved by contour elevation for an extremely large skull defect was smaller than that achieved for a large skull defect. Conclusions: The 3D CAD skull model contour elevation method can be effectively used to simulate the extent of a space-occupying swollen brain and to quantitatively assess the extent of brainstem protection in terms of volume augmentation and volume-increasing rate following DC. As the tangential diameter (representing the degree of DC) exceeded the plateau value, volumetric augmentation was attenuated. However, an increasing volumetric augmentation was detected before the plateau value was reached.
Key Performance Indicators Related to Strength, Endurance, Flexibility, Anthropometrics, and Swimming Performance for Competitive Aquatic Lifesaving

The aim of the study was to investigate key performance indicators for the individual pool-based disciplines of competitive lifesaving regarding strength, flexibility, sprint and endurance swimming performance, anthropometric characteristics, and technical skills specific to competitive lifesaving. Data were collected from Swiss national team members (seven males: age 19 ± 2 yrs, body mass 77 ± 11 kg, body height 177 ± 7 cm and seven females age 21 ± 5 yrs, body mass 64 ± 6 kg, body height 171 ± 4 cm) competing at the 2019 European lifesaving championships. Potential key performance indicators were assessed with race times derived from the 2019 long-course season using Spearman’s correlation coefficient. Large and significant correlations showed that sprint, i.e., 50 m freestyle performance (r ≥ 0.770), was related to race time of all pool-based disciplines, rather than endurance swimming performance. Additionally, significant correlations revealed upper body strength, i.e., bench press (r ≥ −0.644) and pull (r ≥ −0.697), and leg strength (r ≥ −0.627) as key performance indicators. Importance of the lifesaving-specific skills, anthropometric characteristics, and core strength varied between the disciplines. Flexibility was not significantly related to race times of competitive lifesaving. The present study showed that sprint swimming performance, upper body, and leg strength are particularly important for competitive lifesaving. As other physical and technical requirements varied between the pool-based disciplines, coaches may use the present key performance indicators to establish training guidelines and conditioning programs as well as prioritize skill acquisition in training to specifically prepare athletes for their main disciplines.
Changes in Electrical Conductance of Polymer Composites Melts Due to Carbon Nanofiller Particles Migration

In this work, the results of investigation of the effect of polymer composite melts electrical conductance increase with time are presented. The conductance time dependencies were obtained for composites based on polypropylene filled with carbon nanoparticles of different types. The dependencies were analyzed to demonstrate the possibility of correlation of the conductance kinetics with different composite parameters, such as the filler geometry. Additional studies were carried out, such as electron microscopy study, conductance measurements after consecutive surface layer removal, and composite melt conductance measurements using a three-electrode scheme. The results showed that the increased electrical conductance of the composite materials can be attributed to the formation of an enriched with the filler particles surface layer, which happens during the stay of the composite in a melt state. Analysis of the experimental data, along with the results of numerical modeling, allowed to suggest a possible filler distribution transformation scheme. The physical premises behind the investigated effect are discussed.
Modelling the Extraction of Pectin towards the Valorisation of Watermelon Rind Waste

Watermelon is the second largest fruit crop worldwide, with great potential to valorise its rind waste. An experimental design was used to model how extraction parameters (temperature, pH, and time) impact on the efficiency of the process, purity, esterification degree, monosaccharide composition and molar mass of watermelon rind pectin (WRP), with an insight on changes in their structural properties (linearity, branching degree and extraction severity). The models for all responses were accurately fitted (R2 > 90%, lack of fit p ≥ 0.05) and experimentally validated. At optimum yield conditions, WRP yield (13.4%), purity (540 µg/g galacturonic acid) and molar mass (106.1 kDa) were comparable to traditional pectin sources but showed a higher branching degree with longer galactan side chains and a higher protein interaction. Harsher conditions (pH 1) generated purer homogalacturonan fractions with average molar masses (80 kDa) at the expense of yield, while mild extraction conditions (pH ≥ 2) produced highly branched entangled pectin structures. This study underlines novel compositional features in WRP and the possibility of producing novel customized pectin ingredients with a wider potential application scope depending on the targeted structure.
Sirolimus Pharmacokinetics Variability Points to the Relevance of Therapeutic Drug Monitoring in Pediatric Oncology

Sirolimus is widely used in transplantation, where its therapeutic drug monitoring (TDM) is well established. Evidence of a crucial role for sirolimus in the PI3K/AkT/mTor pathway has stimulated interest in its involvement in neoplasia, either as monotherapy or in combination with other antineoplastic agents. However, in cancer, there is no consensus on sirolimus TDM. In the RAPIRI phase I trial, the combination sirolimus + irinotecan was evaluated as a new treatment for refractory pediatric cancers. Blood sampling at first sirolimus intake (D1) and at steady state (D8), followed by LC/MS2 analysis, was used to develop a population pharmacokinetic model (Monolix® software). A mono-compartmental model with first-order absorption and elimination best fit the data. The only covariate retained for the final model was “body surface area” (D1 and D8). The model also demonstrated that 1.5 mg/m2 would be the recommended sirolimus dose for further studies and that steady-state TDM is necessary to adjust the dosing regimen in atypical profiles (36.4% of the population). No correlation was found between sirolimus trough concentrations and efficacy and/or observed toxicities. The study reveals the relevance of sirolimus TDM in pediatric oncology as it is needed in organ transplantation.
Laryngeal mucous membrane pemphigoid serves as a prognostic factor for poor response to treatment with rituximab

Mucous membrane pemphigoid (MMP) is an autoimmune blistering, scarring and occasionally mutilating disease that may progress to blindness or airway obstruction. Over the past few years, rituximab (RTX) has emerged as a potential therapeutic solution for MMP; however, the literature regarding its efficacy in the treatment of severe MMP is sparse. We studied four patients with recalcitrant MMP who were treated with RTX. Three of these had recalcitrant laryngeal disease; two were unresponsive to RTX, while the third patient achieved complete remission (CR) but relapsed twice. The fourth patient, who had oral and ocular disease, also achieved CR. In addition, we reviewed 143 cases of MMP treated with RTX reported in the literature to date. Of these, 120 had late observation endpoints, of whom 81 (67.5%) achieved CR, 24 (20%) received partial remission and 15 (12.5%) had no remission. Based on this study, the presence of laryngeal MMP seems to predict refractoriness to RTX treatment. In conclusion, we found that RTX can ameliorate the MMP course and that laryngeal involvement, which is known to be a prognostic factor for severe MMP, may also predict poor response to RTX.