Search Results (565)

Pelvic organ prolapse (POP) is a prevalent condition, affecting women all over the world, and is commonly treated through surgical interventions that present limitations such as recurrence or complications associated with synthetic meshes. In this study, biodegradable poly($ϵ$-caprolactone) (PCL) cog threads are proposed as a minimally invasive alternative for vaginal wall reinforcement. A custom cutting tool was developed to fabricate threads with varying barb angles (90°, 75°, 60°, and 45°), which were produced via Melt Electrowriting. Their mechanical behavior was assessed through uniaxial tensile tests and validated using finite element simulations. The results showed that barb orientation had minimal influence on tensile performance. In simulations of anterior vaginal wall deformation under cough pressure, all cog thread configurations significantly reduced displacement in the damaged tissue model, achieving values comparable to or even lower than those of healthy tissue. A ball burst simulation using an anatomically accurate model further demonstrated a 13% increase in reaction force with cog thread reinforcement. Despite fabrication limitations, this study supports the biomechanical potential of 3D-printed PCL cog threads for POP treatment, and lays the groundwork for future in vivo validation. Full article

In this study, multicomponent PLA-based biocomposites were developed. In particular, both native fibrous cellulose and cellulose with modified morphology obtained through ball milling treatments were incorporated into the polyester matrix in combination with an oligomeric plasticizer, specifically a lactic acid oligomer (OLA). The resulting materials were analyzed in terms of their morphology, thermal and mechanical properties over time, water vapor permeability, and degradation under soil burial conditions in comparison to neat PLA and unplasticized PLA/cellulose composites. The cellulose phase significantly affected the mechanical properties and enhanced their long-term stability, addressing a common limitation of PLA/plasticizer blends. Additionally, water vapor permeability increased in all composites. Finally, the ternary systems exhibited a significantly higher degradation rate in soil burial conditions compared to PLA, evidenced by larger weight loss and reduction in the molecular weight of the PLA phase. The degradation rate was notably influenced by the morphology of the cellulose phase. Full article

Chromosomal microarray analysis (CMA) was performed for 40 patients with B-ALL undergoing treatment according to the ALL-2016 protocol to investigate the copy number alterations (CNAs) and copy neutral loss of heterozygosity (cnLOH) associated with minimal residual disease (MRD)-positive remission. Aberrations involving over 20,000 genes were identified, and a random forest approach was applied to isolate a subset of genes whose CNAs and cnLOH are significantly associated with poor therapeutic response. We have assembled the triple matched healthy population data and used that data as a reference, but not as a matched control. We identified a recurrent cluster of cnLOH in the 19q13.2–19q13.31 region, significantly enriched in MRD-positive patients (70% vs. 47% in the reference group vs. 16% in MRD-negative patients). This region includes the pregnancy-specific glycoprotein (PSG) gene family and the oncogene ERF, suggesting a potential role in leukemic persistence and treatment resistance. Additionally, we observed significant deletions involving 7p22.3 and 16q13, often as part of large-scale losses affecting almost the entire chromosomes 7 and 16, indicative of global chromosomal instability. These findings highlight specific genomic regions potentially involved in therapy resistance and may contribute to improved risk stratification in B-ALL. Our findings emphasize the value of high-resolution CMA in diagnostics and risk stratification and suggest that PSG genes and other candidate genes could serve as biomarkers for predicting treatment outcomes. Full article

Background: In childhood acute lymphoblastic leukemia (ALL), in addition to classical chromosomal abnormalities, loss of heterozygosity (LOH), including copy-neutral LOH, is also observed. While LOH has been described in the literature, its clinical relevance in pediatric ALL remains unclear. The aim of this study is to identify and analyze patterns of LOH, assess their frequency, and evaluate their association with clinical characteristics and early treatment response during the induction phase of the ALL protocol. Methods: The study included 853 pediatric ALL patients, of whom 120 had B-ALL LOH+ and 58 had T-ALL LOH+. LOH was analyzed using CytoScan HD SNP microarrays. Patients were stratified using multiple correspondence analysis (MCA) and hierarchical clustering on principal components (HCPC), which identified three genetically and clinically distinct clusters. Results: In B-ALL, two clusters with extensive LOH—particularly involving chromosome 9—were associated with poor prognosis and suboptimal response to therapy. In contrast, Cluster 2, characterized by CDKN2A duplication and rare LOH, showed a favorable clinical course. In T-ALL, Cluster 1 had LOH in CDKN2A but favorable outcomes; Cluster 2 exhibited biallelic CDKN2A deletion and aggressive disease; Cluster 3 lacked CDKN2A alterations and showed a genetically stable profile. LOH was common on chromosomes not typically affected by trisomy and rare on those gained. Conclusions: Our study indicates that LOH profiling can positively influence patient stratification by identifying high-risk subgroups, inform prognosis by highlighting unfavorable genetic alterations, and help predict poor treatment response in specific clinical profiles. Full article

Obstructive sleep apnea (OSA) is a prevalent and heterogeneous sleep disorder associated with significant health and societal burdens. While continuous positive airway pressure (CPAP) remains the gold standard treatment, its limitations in adherence and patient tolerance have highlighted the need for alternative therapies. Positional therapy (PT), which targets apneas that occur predominantly in the supine position, has emerged as a promising option for individuals with positional OSA (POSA). This narrative review synthesizes the current literature on PT, examining its clinical indications, typologies, comparative efficacy with CPAP, oral appliances, and hypoglossal nerve stimulation, as well as data on adherence and barriers to long-term use. Traditional methods such as the tennis ball technique have largely been replaced by modern vibrotactile devices, which demonstrate improved comfort, adherence, and comparable short-term outcomes in selected POSA subjects. While PT remains inferior to CPAP in reducing overall AHI and oxygen desaturation, it performs favorably in terms of mean disease alleviation (MDA) and sleep continuity. Importantly, treatment effectiveness is influenced by both anatomical and non-anatomical traits, underscoring the need for accurate phenotyping and individualized care. PT should be considered within a broader patient-centered model that incorporates preferences, lifestyle, and motivational factors. Further research is needed to validate long-term efficacy, optimize selection criteria, and integrate PT into personalized OSA management strategies. Full article

Mitochondria are critical for cellular energy, and while large deletions in their genome (mtDNA) are linked to primary mitochondrial diseases, their significance in cancer is less understood. Given cancer’s metabolic nature, investigating mtDNA deletions in tumors at various stages could provide insights into disease origins and treatment responses. In this study, we analyzed 148 bone marrow samples from 129 pediatric patients with B-cell (B-ALL) and T-cell (T-ALL) acute lymphoblastic leukemia at diagnosis, remission, and relapse using long-range PCR, next-generation sequencing, and the Splice-Break2 pipeline. Both T-ALL and B-ALL exhibited significantly more mtDNA deletions than did the controls, with T-ALL showing a ~100-fold increase and B-ALL a ~15-fold increase. The T-ALL samples also exhibited larger deletions (median size > 2000 bp) and greater heterogeneity, suggesting increased mitochondrial instability. Clustering analysis revealed distinct deletion profiles between ALL subtypes and across disease stages. Notably, large clonal deletions were detected in some B-ALL remission samples, including one affecting up to 88% of mtDNA molecules, which points toward treatment-driven selection or toxicity. A multivariate analysis confirmed that disease type, timepoint, and WHO subtype significantly influenced mtDNA deletion metrics, while age and gender did not. These findings suggest that mtDNA deletion profiling could serve as a biomarker for pediatric ALL and may indicate mitochondrial toxicity contributing to late effects in survivors. Full article

Background: Cold feet syndrome is characterized by hypersensitivity of sympathetic nerves to cold stimuli, resulting in vasoconstriction and reduced peripheral blood flow. This condition causes an intense cold sensation, particularly in the extremities. Although hormonal changes (e.g., during childbirth or menopause) and psychological stress have been implicated, the mechanisms and effective treatments remain unclear. Methods: Ninety adult volunteers were randomized into three groups based on the type of heating mat applied to the feet, with surface temperatures gradually increased from 20 °C to 50 °C. Group A (control) used non-FIR electric mats, Group B used carbon FIR mats, and Group C used loess bio-ball FIR mats. Blood flow (mL/min/100 g) and epidermal temperature (°C) in the left big toe (LBT) and right big toe (RBT) were measured before and after heating or FIR exposure using laser Doppler flowmetry and infrared thermometers. Results: No significant changes in blood flow or skin temperature were observed in Group A. In Group B, blood flow increased by 15.07 mL/min/100 g in the LBT (from 4.12 ± 2.22 to 19.19 ± 5.44) and by 14.55 mL/min/100 g in the RBT (from 4.26 ± 2.29 to 18.81 ± 4.29). In Group C, blood flow increased by 32.86 mL/min/100 g in the LBT (from 4.23 ± 1.64 to 37.09 ± 6.04) and by 32.63 mL/min/100 g in the RBT (from 4.20 ± 1.61 to 36.83 ± 6.48). Epidermal temperature also increased significantly in Group C. All changes in Groups B and C were statistically significant (p < 0.05), with Group C showing the most prominent enhancement. Conclusions: The loess bio-ball mat significantly increased both peripheral blood flow and epidermal temperature compared to the electric and carbon mats. These findings suggest that FIR emitted from loess bio-balls may enhance peripheral circulation through hypothalamus thermogenic response and nitric oxide (NO)-dependent pathways and could serve as a complementary and non-invasive intervention for individuals with poor blood flow. Full article

The friction surfacing (FS) process has emerged over the past few years as a method for joining both similar and dissimilar materials, for volume damage repair of defective components, and for corrosion protection. The possibility to produce a metallic coating by FS, without melting the material, classifies this technique as distinct from other standard methods. This unconventional deposition method is based on the severe plastic deformation that appears on a rotating metallic rod (consumable material) pressed against the substrate under an axial load. The present study aims to investigate the tribological properties and corrosion resistance provided by the aluminum-based FS coatings deposited onto a structural S235 steel substrate and further modified by plasma electrolytic oxidation (PEO). During the PEO treatment, the formation of a ceramic film is enabled, while the hardness, chemical stability, corrosion, and wear resistance of the modified surfaces are considerably increased. The morpho-structural characteristics and chemical composition of the PEO-modified FS coatings are further investigated using scanning electron microscopy combined with energy dispersive spectroscopy analysis and X-ray diffraction. Dry sliding wear testing of the PEO-modified aluminum-based coatings was carried out using a ball-on-disc configuration, while the corrosion resistance was electrochemically evaluated in a 3.5 wt.% NaCl solution. The corrosion rates of the aluminum-based coatings decreased significantly when the PEO treatment was applied, while the wear rate was substantially reduced compared to the untreated aluminum-based coating and steel substrate, respectively. Full article

The paper deals with the issue of obtaining iron-sulfur-containing binders through their mechanochemical treatment using mutual neutralization and detoxification structure formation, and the curing stage of arbolite concrete composites based on industrial waste under long-term loading were also studied. Due to abrasion and impact, the mutual neutralization and detoxification methods of industrial waste toxic components through their mechanochemical treatment on the structures of ball mill LShM-750, were used to obtain iron-sulfur-containing binders. Pyrite cinders acted as oxidizing agents, and elementary technical sulfur had reduced properties. To determine the rate of creep strain growth, the load on prism samples was applied in the form of specially made spring units at stress levels of 0.15 R_bn, 0.44 R_bn, and 0.74 R_bn, where R_bn is the prism strength of iron-sulfur-containing arbolite concrete in compression. The strength and fracture formations of lightweight iron-sulfur concrete were studied using strain gauge apparatus and depth strain gauges glued on shredded reed fibers using adhesive, installed before concreting. It was revealed that the introduction of a sulfur additive within the range from 10 to 13% increases the compressive strength of iron-sulfur-containing concrete composites prepared with that of mortars at a water/solid ratio equal to 0.385 in wet and dry states. It is found that the deformations occurring under applied load growth proportionally to it, and deviation from this regularity was observed for lightweight iron-sulfur-containing concrete only at high compressive stresses. It was also proved that the destruction of iron-sulfur-containing arbolite occurs sequentially. First, the destruction of the mortar component is observed, and then the organic aggregate in the form of crushed reed fiber is destroyed. It was confirmed that arbolite concrete composite can be used as an effective wall material for civil engineering structure, especially in seismic regions of Kazakhstan. Full article

Background/Objectives: In adults with B-cell acute lymphoblastic leukemia (B-ALL), central nervous system (CNS) involvement represents a significant clinical challenge due to its association with adverse outcomes. Infiltration of blast cells into the CNS is primarily detected via cerebrospinal fluid (CSF) microscopy, the current gold standard diagnostic method, although it has limitations in terms of sensitivity. Quantitative polymerase chain reaction (qPCR) offers higher sensitivity and can support the diagnosis of CNS infiltration. This study assessed the mRNA expression levels of CD79A and IL7R in CSF to evaluate their potential for detecting CNS involvement in adults with B-ALL. Methods: CSF samples were collected from adults with B-ALL. The classification criteria for CNS Leukemia (CNS status) were used to evaluate CNS involvement. RNA was extracted from the CSF, and quantitative reverse transcription PCR (RT-qPCR) was used to measure the CD79A and IL7R mRNA expression levels. Results: A total of 19 treatment-naïve adult patients with B-ALL were enrolled over a 19-month period. Four (21%) patients had CNS3 status. Four (21%) patients had CNS3 status. The results also showed that the expression levels of CD79A and IL7R mRNA were significantly higher (median fold change = 0.62 and 2.12, p < 0.05, respectively) in the group with CNS3. Furthermore, using the Haldane-Anscombe correction and Fisher’s exact test, we demonstrated an association between IL7R and CNS3 expression (odds ratio = ∞, due to zero CNS+ in the IL7R group, p < 0.05). Conclusions: CD79A and IL7R mRNA levels in CSF could be potential biomarkers for detecting CNS involvement in adult patients with B-ALL. Full article

In B-cell chronic lymphocytic leukemia (B-CLL), hypodiploidy is a rare but aggressive subtype of the disease with a very bad prognosis. Hypodiploidy, in contrast to normal B-CLL chromosomal aberrations, is marked by widespread genomic instability, which promotes treatment resistance and quick illness development. Its persistence after treatment implies that chromosomal loss gives cancerous clones a selection edge, which is made worse by telomere malfunction and epigenetic changes. Since thorough genetic profiling has a major impact on patient outcomes, advanced diagnostic methods are crucial for early detection. Treatment approaches must advance beyond accepted practices because of its resistance to traditional medicines. Hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor (CAR) T-cell therapy are two potential new therapeutic modalities. Relapse and treatment-related morbidity continue to be limiting concerns, despite the noteworthy improvements in outcomes in high-risk CLL patients receiving HSCT. Although more research is required, CAR T-cell treatment is effective in treating recurrent B-ALL and may also be used to treat B-CLL with hypodiploidy. Novel approaches are essential for enhancing patient outcomes and redefining therapeutic success when hypodiploidy challenges established treatment paradigms. Hypodiploidy is an uncommon yet aggressive form of B-CLL that has a very bad prognosis. Hypodiploidy represents significant chromosomal loss and structural imbalance, which contributes to a disordered genomic environment, in contrast to more prevalent cytogenetic changes. This instability promotes resistance to certain new drugs as well as chemoimmunotherapy and speeds up clonal evolution. Its persistence after treatment implies that hypodiploid clones have benefits in survival, which are probably strengthened by chromosomal segregation issues and damaged DNA repair pathways. Malignant progression and treatment failure are further exacerbated by telomere erosion and epigenetic dysregulation. The need for more sensitive molecular diagnostics is highlighted by the fact that standard karyotyping frequently overlooks hypodiploid clones, particularly those concealed by endoreduplication, despite the fact that these complications make early and correct diagnosis crucial. Hypodiploidy requires a move toward individualized treatment because of their link to high-risk genetic traits and resistance to conventional regimens. Although treatments like hematopoietic stem cell transplantation and CAR T-cells show promise, long-term management is still elusive. To improve long-term results and avoid early relapse, addressing this cytogenetic population necessitates combining high-resolution genomic technologies with changing therapy approaches. Full article

In this study, we investigate the environmental stability of the sulfide-based argyrodite solid electrolyte Li₆PS₅Cl₀.₅Br₀.₅, a promising candidate for all-solid-state lithium batteries due to its high ionic conductivity and favorable mechanical properties. Despite its potential, the material’s sensitivity to ambient air humidity presents challenges for large-scale battery manufacturing. Moisture exposure leads to performance degradation and the release of toxic hydrogen sulfide (H₂S) gas, raising concerns for workplace safety. The objectives of this study are to validate the electrolyte synthesis process, evaluate the effects of air humidity exposure on its reactivity and ionic conductivity, and establish a standardized protocol for assessing environmental stability. We report a synthesis method based on ball milling and heat treatment that achieves an ionic conductivity of 2.11 mS/cm, along with a fundamental study incorporating modeling and formulation approaches to evaluate the electrolyte’s environmental stability. Furthermore, we introduce a simplified testing method for assessing environmental stability, which may serve as a benchmark protocol for the broader class of argyrodite solid electrolytes. Full article

This study examines the mechanical and microstructural properties of graphene-reinforced AA2219 composites developed for hydrogen storage tank inner liner applications. A novel processing route combining high-energy ball milling, ultrasonic-assisted stir casting, and squeeze casting was used to achieve homogeneous dispersion of 0.5 wt.% graphene nanoplatelets and minimise agglomeration. The composites were subjected to T6 and T8 ageing treatments to optimize their properties. Microstructural analysis revealed refined grains, uniform Al₂Cu precipitate distribution, and stable graphene retention. Mechanical testing showed that the as-cast composite exhibited a UTS of 308.6 MPa with 13.68% elongation. After T6 treatment, the UTS increased to 353.6 MPa with an elongation of 11.24%. T8 treatment further improved the UTS to 371.5 MPa, with an elongation of 8.54%. Hardness improved by 46%, from 89.6 HV (as-cast) to 131.3 HV (T8). Fractography analysis indicated a shift from brittle to ductile fracture modes after heat treatment. The purpose of this work is to develop lightweight, high-strength composites for hydrogen storage applications. The novelty of this study lies in the integrated processing approach, which ensures uniform graphene dispersion and superior mechanical performance. The results demonstrate the suitability of these composites for advanced aerospace propulsion systems. Full article

Optical genome mapping (OGM) is a novel, high-resolution technology for genome-wide detection of structural variants, offering clear advantages over conventional cytogenetics in hematologic malignancies. We applied OGM to a large cohort of patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDSs), and B-cell acute lymphoblastic leukemia (B-ALL) to evaluate its clinical utility. In AML and MDS, it revealed high-risk alterations such as deletions in 5q31–5q32 and 7q22, and cryptic fusions like NUP98::NSD1 that were missed by karyotyping or FISH. It also identified chromoanagenesis, a catastrophic chromosomal event linked to poor prognosis and often undetectable by standard methods. In B-ALL, OGM uncovered clinically relevant deletions in CDKN2A/B, PAX5, and IKZF1, as well as high-risk ploidy changes like hypodiploidy and hyperdiploidy, all important for risk assessment and frequently underdetected. OGM not only refines diagnosis and improves risk stratification but can also uncover cryptic and complex genomic abnormalities. Our findings support its integration into routine diagnostics to enhance classification, guide treatment decisions, and improve patient outcomes. Full article

Firework-related injuries remain a serious public health issue in Germany, especially during New Year’s Eve. While many injuries are minor, the misuse of illegal or homemade fireworks can cause severe trauma resembling military combat injuries and can heavily burden emergency services. Notably, injury rates declined during the COVID-19 firework bans, underscoring the impact of preventive measures. We report two cases of young males with severe injuries from illicit fireworks. The first is a case of a 16-year-old that detonated an illegal Polish firework ball bomb, sustaining 9% total body surface area (TBSA) burns (second- to third-degree), hand fractures, compartment syndrome of the hand, and soft-tissue trauma. He underwent multiple surgeries, including fasciotomy, osteosynthesis, and skin grafting. The other case presented is a 19-year-old man who was injured by a homemade device made of bundled firecrackers, suffering deep facial and bilateral hand burns. He required prolonged ventilation, surgical debridement, and treatment with Kerecis^® fish skin and Epicite^® dressings. Both required intensive ICU care, interdisciplinary management, and lengthy rehabilitation. Total hospital costs amounted to €58,459.52 and €94,230.23, respectively, as calculated according to the standardized German DRG. These cases illustrate the devastating impact of illegal fireworks. The devastating consequences of explosive trauma are often difficult to treat and may lead to long-term functional and psychological impairments. Prevention through public education, stricter regulations, and preparedness is essential. Pandemic-era injury reductions support sustained policy efforts. Full article