Search Results (372)

Partial cystectomy is a surgical bladder-sparing option for selected patients with muscle-invasive bladder cancer (MIBC), urachal adenocarcinoma and diverticular bladder tumors. Partial cystectomy hold several advantages. It allows for definite pathology and accurate staging while avoiding side effects from radiation therapy and preserves the option for salvage radical therapy (radical cystectomy or radical radiotherapy). Patients should have a CT urogram, prostatic urethral biopsy and mapping biopsies or blue light cystoscopy to rule out multifocal disease or CIS. Small solitary MIBC patients without carcinoma in situ in an area of the bladder where resection can be performed with negative margin would be the ideal candidates for partial cystectomy. Neoadjuvant systemic therapy is recommended for patients undergoing partial cystectomy. Partial cystectomy can be performed either by open or robotic approaches. When compared to radical cystectomy, partial cystectomy affords a lower complication rate and length of stay and better quality of life. Recurrence-free survival, cancer-specific survival and overall survival at 5 years is 39–67%, 62–84% and 45–70%, respectively. Following partial cystectomy, patients should have three monthly cystoscopy and urinary cytology for the first 24 months followed by 6-monthly cystoscopy for year 3 and 4 and then yearly for life. Cross-sectional imaging should be performed every 3–6 months for the first 2–3 years and then annually for 5 years. Full article

Electric mountain bikes (eMTBs) demand compact, high-torque motors capable of handling steep terrain and variable load conditions. Surface-mounted permanent magnet synchronous motors (SPMSMs) are widely used in this application due to their simple construction, ease of manufacturing, and cost-effectiveness. However, SPMSMs inherently lack reluctance torque, limiting their torque density and performance at high speeds. While interior PMSMs (IPMSMs) can overcome this limitation via reluctance torque, they require complex rotor machining and may compromise mechanical robustness. This paper proposes a surface-inset PMSM topology as a compromise between both approaches—introducing reluctance torque while maintaining a structurally simple rotor. The proposed motor features inset magnets shaped with a tapered outer profile, allowing them to remain flush with the rotor surface. This geometric configuration eliminates the need for a retaining sleeve during high-speed operation while also enabling saliency-based torque contribution. A baseline SPMSM design is first analyzed through finite element analysis (FEA) to establish reference performance. Comparative simulations show that the proposed design achieves a 20% increase in peak torque and a 33% reduction in current density. Experimental validation confirms these findings, with the fabricated prototype achieving a torque density of 30.1 kNm/m³. The results demonstrate that reluctance-assisted torque enhancement can be achieved without compromising mechanical simplicity or manufacturability. This study provides a practical pathway for improving motor performance in eMTB systems while retaining the production advantages of surface-mounted designs. The surface-inset approach offers a scalable and cost-effective solution that bridges the gap between conventional SPMSMs and more complex IPMSMs in high-demand e-mobility applications. Full article

This study systematically investigates the impact of Cu²⁺ doping on the structural, magnetic, and magnetocaloric properties of Cu_xCo_1−xCr₂O₄ nanoparticles synthesized via a solution combustion method. Cu incorporation up to x = 20% induces a progressive structural transformation from a cubic spinel to a trigonal corundum phase, as confirmed by X-ray diffraction and Raman spectroscopy. The doping process also leads to increased particle size, improved crystallinity, and reduced agglomeration. Magnetic measurements reveal a transition from hard to soft ferrimagnetic behavior with increasing Cu content, accompanied by a notable rise in the Curie temperature from 97.7 K (x = 0) to 140.2 K (x = 20%). The magnetocaloric effect (MCE) is significantly enhanced at higher doping levels, with the 20% Cu-doped sample exhibiting a maximum magnetic entropy change (−ΔS_M) of 2.015 J/kg-K and a relative cooling power (RCP) of 58.87 J/kg under a 60 kOe field. Arrott plot analysis confirms that the magnetic phase transitions remain second-order in nature across all compositions. These results demonstrate that Cu doping is an effective strategy for tuning the magnetostructural response of CoCr₂O₄ nanoparticles, making them promising candidates for low-temperature magnetic refrigeration applications. Full article

Defibrotide, which is approved for treating hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), exhibits pleiotropic anti-inflammatory, anti-thrombotic, and fibrinolytic properties, conferring broad endothelial protective effects. Given these mechanisms, defibrotide has potential utility in various conditions involving endothelial injury or activation. In this review we outline the endothelial-protective mechanisms of defibrotide and comprehensively summarize current evidence supporting its applications in hematologic malignancies, including the prevention and treatment of hepatic VOD/SOS, graft-versus-host disease, and transplant-associated thrombotic microangiopathy. Additionally, we discuss its role in mitigating key toxicities linked to chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We also explore emerging evidence on defibrotide’s potential in SARS-CoV-2 infection-associated endotheliopathies, including acute COVID-19 and post-acute sequelae of SARS-CoV-2 infection (“long-COVID”), and the endothelial protective activity of defibrotide in these settings. Finally, we highlight potential future applications of defibrotide in hematologic malignancies and viral infections, emphasizing its multimodal mechanism of action. Full article

Authentic learning opportunities that simulate full-scale design and construction using real materials provide valuable experiential learning environments for construction and civil engineering students by challenging students to apply building concepts in practical settings. These activities challenge students to apply theoretical concepts in a realistic, hands-on context. However, the excessive cost of real building materials required for this mode of education limits access to the vast majority of students. As a result, educational researchers have explored potential alternatives to provide cost-effective experiential learning through activities using mock-up materials (e.g., plastic straws and popsicle sticks) and a simulation of experiences using immersive technologies (e.g., virtual reality or augmented reality). While some of these alternatives approximate the environment and others provide physical interaction with mock-up materials, the lack of authenticity in the building materials used introduces some apparent differences between the “authentic” learning environments and their cost-effective approximations. Therefore, this research aims to identify the learning processes reported by students and faculty who participated in authentic learning experiences to understand the ways in which this mode of education offers unique value to construction education. Their interview responses illustrated characteristics of authentic learning experiences that were believed to be critical to the learning process, some of which included working in groups; interdisciplinary participants; and the use of real construction materials. Although some of these characteristics are intrinsically linked to the use of real materials, others do not explicitly refer to interaction with real materials. This may point to specific aspects of authentic learning that educational researchers can replicate or enhance to provide cost-effective learning environments, such as virtual or augmented reality. The contribution of this paper is in identifying the characteristics of authentic learning experiences that may guide educational investment and research innovations that aim to replicate some of these learning experiences through more accessible learning environments. Full article

Circulating tumour DNA (ctDNA) is a promising biomarker for personalised oncology. However, its clinical utility is limited by detection sensitivity, particularly in early-stage disease. T-Oligo Primed Polymerase Chain Reaction (TOP-PCR) is a commercial amplification approach utilising an efficient “half-adapter” ligation design and a single-primer-based PCR strategy. This study evaluated the clinical value and application of cell-free DNA (cfDNA) pre-amplification. cfDNA amplification with TOP-PCR preserved DNA size profiles and resulted in a 22 bp size increase due to the half-adaptor ligation. Gene target amplification rates varied, showing lower efficiency for the GC-rich TERT promoter amplicon and higher efficiency for the BRAF and TP53 amplicons. Optimised pre-amplification (20 ng cfDNA input and 5–7 cycles of PCR) enhanced ctDNA detection sensitivity and expanded sample availability for the detection of multiple tumour-informed mutations. Importantly, PCR errors emerged in pre-amplified cfDNA samples, underscoring the necessity for negative controls and the establishment of stringent mutation positivity thresholds. Full article

To address the surge in Aspergillus fumigatus infections among immunosuppressed patients and azole resistance, this study focused on developing novel inhibitors targeting dihydroorotate dehydrogenase (AfDHODH), a key enzyme in fungal pyrimidine synthesis. The three-dimensional structure of AfDHODH was constructed via homology modeling. Molecular docking, dynamics simulations, and binding free energy calculations systematically elucidated the mechanisms of existing inhibitors. Virtual screening against the ZINC20 and ChEMBL databases yielded 13 candidates, with two micromolar inhibitors (IC₅₀ < 100 μM) identified through in vitro assays. These inhibitors exhibited novel scaffold structures that were distinct from known DHODH inhibitors. The results validate the feasibility of homology modeling-guided antifungal discovery and these findings provide critical insights for the development of new antifungal agents. Full article

Background: Remote symptom monitoring via electronic platforms may identify patients at risk for unplanned acute care visits after surgery. Since 2016, the Memorial Sloan Kettering Cancer Center (MSKCC) has employed the Recovery Tracker (RT), a patient-reported outcome (PRO) system, for symptom monitoring after ambulatory procedures. In 2021, RT was extended to patients undergoing inpatient colorectal surgery. Objective: To evaluate the impact of RT implementation on urgent care utilization and readmission rates in patients undergoing elective inpatient colorectal surgery and to determine whether patient engagement with RT influences these outcomes. Methods: In this retrospective observational study at MSKCC, we compared patients undergoing elective colorectal surgery during the RT implementation period (March 2021–December 2022) to a historical control cohort (February 2019–February 2020). The primary outcome was a potentially unnecessary urgent care center (UCC) visits—defined as a visit not requiring inpatient admission. Secondary outcomes included 30-day readmission and survey engagement. Multivariable logistic regression was used for adjusted comparisons. Results: A total of 1941 patients in the RT cohort and 1206 in the control group met the inclusion criteria. The RT cohort had higher rates of UCC visits without admission (4.43% vs. 1.6%) and 30-day readmissions (9.74% vs. 6.88%). RT period surgery was independently associated with increased odds of UCC visits (OR 2.80, 95% CI 1.71–4.58, p < 0.0001) and readmissions (OR 1.43, 95% CI 1.09–1.88, p = 0.0098). Notably, RT users who completed at least one survey (70.2%) had significantly lower odds of readmission (OR 0.56, 95% CI 0.41–0.77, p = 0.0003) compared to non-responders. Discussion: Engagement with the RT system was associated with a 44% reduction in readmission risk, identifying non-responders as a vulnerable subgroup. While the overall rates of post-discharge care utilization increased after RT implementation, active participation in PRO reporting emerged as a protective factor. Conclusions: These findings highlight the need for strategies to promote engagement and support patients less likely to interact with remote monitoring tools. Non-response may signal barriers such as technological challenges or increased vulnerability, warranting proactive engagement strategies. Full article

Let G be a given bounded multiply connected domain of connectivity $m+1$ bounded by smooth Jordan curves. Koebe’s iterative method is a classical method for computing the conformal mapping from the domain G onto a bounded multiply connected circular domain obtained by removing m disks from the unit disk. Koebe’s method has been generalized to compute the conformal mapping from the domain G onto a bounded multiply connected circular domain obtained by removing $m-1$ disks from a circular ring. A fast numerical implementation of the generalized Koebe’s iterative method is presented in this paper. The proposed method is based on using the boundary integral equation with the generalized Neumann kernel. Several numerical examples are presented to demonstrate the accuracy and efficiency of the proposed method. Full article

Parthanatos, a novel form of programmed cell death mediated by PARP1 and driven by DNA damage, has not been comprehensively characterized in breast cancer (BC). Given the widespread clinical use of PARP1 inhibitors for treating BRCA-mutant breast cancers, understanding the role of parthanatos is crucial. In this study, we systematically analyzed the role and clinical significance of parthanatos in BC by integrating genomic, transcriptomic, and clinical data. Our analysis revealed significant differential expression of parthanatos-related genes between BC and normal breast tissues, with frequent copy number variations (CNVs) affecting gene expression. At the single-cell level, parthanatos-related genes were primarily expressed in breast cancer cells and macrophages, and genomic instability scores were positively correlated with parthanatos pathway scores. Unsupervised clustering identified two BC subtypes based on parthanatos-related gene expression: C1 (parthanatos-high) and C2 (parthanatos-low). C1 exhibited a poorer prognosis, reduced immune infiltration, and potential resistance to PARP inhibitors compared to C2. This study represents the first comprehensive investigation of parthanatos in BC, offering insights into its role in tumor progression and highlighting its potential link to PARP inhibitor resistance and poor clinical outcomes. Full article

Mouse sperm-associated antigen 6-like (SPAG6L) evolved from SPAG6, the mammalian ortholog of Chlamydomonas PF16, which is localized in the central apparatus of the motile cilia and is essential for ciliary motility. Even though the amino acid sequences of the two SPAG6 proteins are highly similar, the two proteins have different biological expression patterns in vivo. No major phenotypes were discovered in the global Spag6 knockout mice. However, the global Spag6l knockout mice demonstrated multiple phenotypes in tissues with and without cilia. Since SPAG6L decorates microtubules and modulates cytoskeleton function, and Sertoli cells have a well-developed microtubule transport network, the potential function of SPAG6L in Sertoli cells was evaluated. The floxed Spag6l mice were crossed with Amh-Cre transgenic mice to inactivate the Spag6l gene specifically in Sertoli cells. Surprisingly, the fertility of the homozygous mutant males was not reduced. The testis size and sperm number and motility showed no significant difference to those of the control mice. Testicular histology also showed normal spermatogenesis. No significant changes were observed in the number of Sertoli cells and blood–testis barrier function. Our study showed that the inactivation of only Spag6l does not affect Sertoli cell function during the first 6 months of life. Full article

Polyethylene terephthalate (PET) is commonly used in beverage container manufacturing; however, its classification as a single-use plastic significantly contributes to environmental pollution. Improper disposal results in enduring contamination of both terrestrial and marine ecosystems, which poses ecological and health risks. Among the disposal methods, recycling, incineration, and landfilling, only recycling promotes a circular economy by reducing reliance on landfills, alleviating emissions, and conserving fossil resources. This study employs the life cycle assessment (LCA) method to evaluate the environmental impacts of three PET bottle recycling facilities in Taiwan, considering collection, transportation, and processing in the system boundary. It also assesses the effects of raw material composition, comparing transparent, colored, and mixed PET bottles. The results indicate that facilities processing colorless PET have lower environmental damage values (16.6–18.1 mPt·kg⁻¹ of recycled flakes) than those handling colored and oil-trapped PET (25 mPt·kg⁻¹) due to higher energy demands and poly aluminum chloride usage in wastewater treatment. Granulation was identified as a significant environmental hotspot for recycled PET pellets, with a damage value of 35 mPt·kg⁻¹. Integrating renewable energy and recycled PET into PET bottle manufacturing could significantly reduce their environmental impacts. Policy recommendations include adopting renewable energies as the source energy, calibrating the use of chemicals in recycling facilities, and mandating minimum recycled content in PET products to enhance circularity. Full article

Background/Objectives: Autophagy is a conserved self-degradation process by which cells break down and recycle their cellular constituents. This process is activated by various stressors, including nutrient deprivation and DNA damage, and has also been associated with tumor progression. In the present study, we aimed to determine the expression patterns, clinicopathological significance, and prognostic value of the autophagy marker microtubule-associated protein 1 light chain 3 alpha (LC3A)—an essential component of autophagic vacuoles—in rectal cancer. Methods: LC3A reactivity was measured by immunohistochemistry in tumor samples from 243 patients who underwent surgery for rectal cancer. Results: Three distinct patterns of LC3A expression were identified: diffuse cytoplasmic, perinuclear, and stone-like structures (SLS). In Kaplan–Meier survival analyses, patients positive for the SLS pattern of LC3A staining in the tumor periphery (TP) had worse overall survival (OS; p = 0.001) and disease-free survival (DFS; p = 0.030) than those without SLSs in this region, as determined by the log–rank test. When patients were stratified by tumor stage, this result was significant in those with stage T3–T4 (OS, p < 0.001; DFS, p = 0.001) but not T1–T2 disease. Multivariate Cox regression analysis further showed an association between TP-localized LC3A SLS positivity and reduced OS for the overall cohort (hazard ratio [HR] = 2.6313, 95% confidence interval [CI]: 1.090–6.349, p = 0.031) and specifically those in the T3–T4 subgroup (HR = 3.347, 95% CI: 1.657–6.760, p = 0.001). Conclusions: Our findings suggest that positivity for SLSs in the TP may hold clinical value as a biomarker for survival prognosis in rectal cancer patients. Full article

Background/Objectives: Early intervention combining nutrition optimisation with exercise can potentially prevent frailty progression and reverse pre-frailty in older adults. Methods: This 4-month study examined the effectiveness of nutrition education (without oral nutrition supplement use) as part of a multi-domain intervention on the nutritional status and intake of pre-frail community-dwelling older adults and its relationship with sarcopenia markers. Results: Amongst 172 participants (≥55 years), 5.8% were malnourished, with no significant change in nutritional status throughout the study. Post-intervention, participants consumed significantly higher daily calories, protein, protein per body weight (BW), and calcium (p < 0.001); protein intake at lunch (p = 0.001) and dinner (p = 0.004) also increased. However, 6-month post-intervention daily protein (p = 0.025), protein per BW (p = 0.039), and calcium (p = 0.015) decreased significantly. Sarcopenia markers (handgrip strength (HGS), five-time chair stand test (5STS), and short physical performance battery score (SPPB)) showed no significant difference post-intervention. Well-nourished participants had better HGS (p = 0.005), 5STS (p = 0.026), and SPPB (p = 0.039). Practical nutrition education effectively improved nutritional intake, but the effect was not sustained 6-months post-intervention. Conclusions: Optimising nutritional status with a focus on improving protein intake, especially at breakfast, to meet minimal intake to stimulate muscle protein synthesis can help prevent sarcopenia and frailty. Future studies should examine factors driving sustainable improvement to prevent frailty progression in this population. Full article

This study explores biochar’s impact on soil fertility, greenhouse gas (GHG) emissions, grain yield, carbon footprint (CF), and net ecosystem carbon budget (NECB) in northwest China’s arid regions. A two-year field experiment tested three biochar rates (15, 30, and 45 t ha⁻¹) against a control. The results showed that biochar significantly reduced overall soil GHG emissions, though the highest rate increased methane emissions. The 30 t ha⁻¹ rate yielded the highest average grain production (13.9 t ha⁻¹), boosted soil organic carbon storage by 76 kg ha⁻¹, and decreased global warming potential (GWP) by 87.8 kg CO₂ ha⁻¹ and GHG emission intensity by 6.74 kg t⁻¹. Biochar also lowered the CF and enhanced the NECB, primarily through increased net primary production and improved soil fertility and crop yields. CO₂ emissions and fertilizer use were major CF contributors, but biochar reduced both the biomass-scaled and yield-scaled CFs. Overall, biochar improved crop yields, NECB, and soil carbon storage while reducing GWP, GHGI, and CF. This study recommends 30 t ha⁻¹ biochar to optimize crop production, enhance carbon balance, and mitigate climate change impacts, highlighting biochar’s potential as a sustainable soil amendment in arid ecosystems. Full article