Search Results (3,021)

This paper develops an operator-oriented framework for spectral approximation in fractional calculus by introducing a fractional inner product defined through the Riemann-Liouville integral. Instead of modifying polynomial families, the proposed approach continuously deforms the underlying Hilbert space structure, with the fractional order $\alpha$ acting as a deformation parameter. A central theoretical result shows that this fractional inner product is mathematically equivalent to a classical weighted inner product with a deformed weight $w_{\alpha }\left(x\right)={(b-x)}^{\alpha -1}w\left(x\right)$. This equivalence establishes a rigorous connection between fractional calculus and classical orthogonal polynomial theory and clarifies the structural role of the fractional parameter. For a canonical one-dimensional setting, explicit recurrence relations are derived and the limiting behavior as $\alpha \to 1$ is characterized, recovering the classical theory. The resulting orthogonal systems are naturally compatible with fractional operators and are used to construct spectral Galerkin methods for fractional differential equations. Well-posed variational formulations and optimal convergence rates are established. Numerical experiments illustrate the effectiveness of the framework, demonstrating spectral accuracy and improved performance in the approximation of fractional integrals and selected fractional differential equations when compared with standard polynomial bases. The proposed formulation provides a unifying operator-level perspective for spectral methods in fractional calculus. Full article

Background/Objectives: Localized renal cell carcinoma (RCC) unfortunately has a suboptimal rate of metastatic recurrence. Immune-checkpoint inhibition (ICI), commonly known as immunotherapy, is being increasingly utilized in the management of other localized cancers. The objective of this paper is to review the most recent literature as it pertains to ICI in localized RCC, highlight major lessons learned across clinical trials, and then suggest new directions based on these lessons and on new technologies. Methods: English-language articles were identified in PubMed/Google Scholar/Scopus. Selection priority was placed on prospective clinical trials. Particular emphasis was placed on disease-free survival (DFS), overall survival (OS), and clinical trial design. Novel approaches to the diagnosis, risk stratification, and management of RCC were also queried. Results: The KEYNOTE-564 trial demonstrated DFS and OS benefits of adjuvant pembrolizumab in high-risk clear cell RCC. Although discordance exists with adjuvant ICI in the IMmotion-010 and CheckMate-914 trials, preliminary data from the RAMPART trial also reveal a DFS benefit for adjuvant durvalumab–tremelimumab. The PROSPER trial failed to show a benefit for perioperative nivolumab, but ongoing neoadjuvant/perioperative ICI trials show promise. Subtle differences in design exist across the mentioned trials and are arguably clinically significant. Several new diagnostic tools and technologies have been identified for use in RCC. Conclusions: By applying the lessons learned from the differences in clinal trial design, along with leveraging new diagnostic tools and technologies, there is great potential to more accurately stratify risk amongst patients with localized RCC and therefore better identify the patients who are most likely to benefit from perioperative ICI. Full article

Background/Objectives: Background parenchymal enhancement (BPE) on breast magnetic resonance imaging reflects hormonal and vascular activity of fibroglandular tissue and is studied as a prognostic marker for breast cancer. This paper serves as a review that evaluates quantitative methods for BPE measurements for predicting treatment outcomes. Methods: PubMed was searched for papers on evaluating BPE with outcomes to compare, such as pathologic complete response, recurrence-free survival, disease-free survival, and overall survival, from 2015 to 2025. In total, eleven papers using quantitative methods to measure BPE were selected. Results: Quantitative results showed that BPE reduction during neoadjuvant chemotherapy and high pre-treatment/baseline BPE are linked to improved treatment response and reduced risk of recurrence. Conclusions: Quantitative assessment methods yield objective and reproducible prognostic information. Incorporating quantitative BPE measurements alongside tumor-focused imaging features may further improve predictive accuracy in clinical settings. Full article

Cervical cancer (CC) remains a major global health challenge due to chemotherapy resistance and recurrence. Mesenchymal stem cell-derived exosomes (MSC-exosomes) have dual roles, as they can act as therapeutic agents and contribute to chemoresistance. However, their role in response to chemotherapy in CC remains unclear. Therefore, our study investigated the effects of MSC-exosome pretreatment on chemotherapy sensitivity using three-dimensional spheroid models generated from HeLa and SiHa CC cell lines. Proteomic profiling of MSC-exosomes identified key proteins, including ANXA1, ANXA2, EEF2, LGALS1, and PKM2, associated with tumor regeneration and chemotherapy response. MSC-exosomes exhibited context-dependent effects in both chemoresistance and chemosensitization by modulating drug efflux, metabolic reprogramming, stress adaptation, apoptosis, DNA damage response, and integrin-mediated signaling. MSC-exosome pretreatment altered spheroid responses to paclitaxel in combination with cisplatin or carboplatin. MSC-exosomes significantly enhanced chemotherapy-induced cytotoxicity in HeLa spheroids, as evidenced by reduced cell viability, increased caspase activity, and upregulation of the pro-apoptotic marker Bax. In contrast, SiHa spheroids represented selective responses: MSC-exosome pretreatment did not enhance sensitivity to paclitaxel–cisplatin but improved responsiveness to paclitaxel–carboplatin, particularly within the spheroid core. Overall, MSC-exosome pretreatment exerts cell type and drug-specific effects in CC spheroids, supporting their potential to modulate chemotherapy response. Full article

Wind energy is a core pillar of global green and sustainable energy transition. However, existing wind power prediction models face three key challenges: traditional long short-term memory (LSTM) models struggle to capture long-term temporal dependencies efficiently and have high training latency, while Transformer-based models exhibit excessive computational complexity and are prone to overfitting for short-term fluctuating data; meanwhile, few models integrate seasonal trend modeling with multi-scale temporal feature extraction, leading to large prediction errors in seasonal transitions. To address these issues, this paper proposes a hybrid prediction framework combining a novel T-LSTM recurrent unit with the Seasonal Autoregressive Integrated Moving Average (SARIMA) model. The T-LSTM unit fuses a simplified Transformer module and an improved LSTM structure. Thus, the design can synergistically capture both short-term fluctuations and long-term dependencies in wind power data. Complementarily, SARIMA is integrated via weighted fusion to model seasonal trends, addressing the neglect of seasonal characteristics in existing deep learning models. A diverse set of benchmark methods for wind power prediction are selected for comparison, including LSTM, convolutional neural network-gated recurrent unit (CNN-GRU), ns_Transformer, Autoformer, Reformer and least squares support vector machine (LSSVM), with experiments conducted across various prediction horizons. The results show that the proposed T-LSTM model outperformed most benchmark methods in key evaluation metrics across multiple prediction horizons and exhibited no statistically significant difference from Autoformer only in the 90 min horizon, validating its superiority in handling complex wind power time series. Full article

Introduction: Bronchiectasis is a chronic, heterogeneous airway disease characterised by irreversible bronchial dilatation, recurrent infections, and persistent inflammation, leading to progressive lung damage, frequent exacerbations, and impaired quality of life. Neutrophil-driven inflammation, largely mediated by excessive activity of neutrophil serine proteases such as neutrophil elastase, represents a central pathogenic mechanism and an important therapeutic target. Methods: Brensocatib, a first-in-class, selective, and reversible inhibitor of dipeptidyl peptidase-1 (DPP-1), prevents the activation of neutrophil serine proteases during neutrophil maturation in the bone marrow. By reducing downstream protease activity, brensocatib modulates aberrant neutrophilic inflammation without broadly suppressing immune function. Results: Clinical studies, including the Phase-2 WILLOW trial and the Phase-3 ASPEN trial, have demonstrated that brensocatib significantly reduces exacerbation frequency, prolongs time to first exacerbation, and lowers sputum neutrophil protease activity, with a favourable safety profile. Importantly, these benefits were observed across multiple patient subgroups and in addition to standard-of-care therapies. Conclusions: As the first FDA-approved (12 August 2025) mechanism-based therapy for non–cystic fibrosis bronchiectasis, brensocatib represents a paradigm shift toward targeted, precision treatment of neutrophil-mediated airway disease. Its clinical efficacy, biomarker-driven rationale, and potential to reduce antibiotic dependence highlight brensocatib as a cornerstone therapy in bronchiectasis management and a promising strategy for other neutrophil-driven inflammatory conditions. Full article

Reoperation for papillary thyroid carcinoma (PTC) requires precise lymph node metastasis assessment, yet ultrasound (US) alone may be insufficient in complex or high-risk cases. This study evaluated whether supplementing US with magnetic resonance imaging (MRI) improves surgical guidance and outcomes in reoperation. We retrospectively analyzed 375 patients who underwent reoperation between 2014 and 2022. Propensity score matching yielded 101 patients in the USUS-only group and 62 in the US+MRI group. Pathological and imaging data were compared to assess diagnostic performance, surgical outcomes, biochemical responses, and recurrence-free survival. The combined approach significantly increased sensitivity for detecting central lymph node metastasis from 52.5% to 90.9% and resulted in higher rates of central neck dissections (65.1% versus 45.5%) with greater lymph node yield (median: 29 versus 20) but lower lymph node ratios. More patients in the combined group achieved excellent biochemical responses (50.0% versus 27.7%). While overall recurrence-free survival (RFS) was not significantly different, the US+MRI group showed improved RFS among patients with ≥2 positive central nodes (HR = 0.24, p = 0.032). Importantly, complication rates were comparable, suggesting that improved outcomes were achieved without added surgical risk. Combined US and MRI assessment enhances diagnostic performance and may improve surgical and oncological outcomes in select high-risk patients undergoing PTC reoperation. Full article

Background: Autoinflammatory bone disorders are rare, non-infectious inflammatory conditions that primarily involve the skeleton, most commonly presenting as chronic nonbacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO). Less frequently, they occur in the context of Mendelian syndromes such as Majeed syndrome, deficiency of the interleukin-1 receptor antagonist (DIRA), and pyogenic arthritis; pyoderma gangrenosum; and acne (PAPA) syndrome. Given the role of IL-1-driven innate immune dysregulation across these bone disorders, and the growing, though heterogeneous, clinical experience with IL-1 blockade, this review maps and critically appraises the available evidence on canakinumab in autoinflammatory bone disorders. Methods: We systematically searched PubMed and the Cochrane Library (English, inception–July 2025) and screened ClinicalTrials.gov. Eligible reports included any case reports/series describing canakinumab use in autoinflammatory bone disorders (CNO/CRMO, Majeed, DIRA, PAPA). Results: Six publications met the inclusion criteria (one case series, five case reports; 10 patients). Complete responses were reported in all three patients with Majeed syndrome and in two patients with sporadic CRMO associated with systemic features. Partial responses occurred in two additional sporadic CRMO cases, while no meaningful response was documented in DIRA. No interventional trials of canakinumab were identified on ClinicalTrials.gov for CNO/CRMO, Majeed, DIRA, or PAPA. Conclusions: Although the role of IL-1 in the pathogenesis of autoinflammatory bone disease provides a rationale for IL-1 blockade, evidence for canakinumab remains limited and heterogeneous, precluding definitive conclusions. Indicators of benefits appear most consistently in Majeed syndrome and in selected CRMO phenotypes. Full article

Immunotherapy has significantly reshaped the management of malignant pleural mesothelioma (MPM), offering new therapeutic opportunities after decades in which platinum–pemetrexed chemotherapy represented the only systemic option. However, clinical benefit remains markedly heterogeneous, with outcomes strongly influenced by histologic subtype, patient characteristics, and real-world treatment conditions. Evidence from monotherapy trials has been inconsistent, whereas combination approaches—particularly nivolumab plus ipilimumab—have demonstrated improved survival compared with chemotherapy, mainly in non-epithelioid tumors. Nevertheless, real-world data consistently show lower efficacy and higher toxicity than registrational studies, especially among elderly and unselected populations. Recent translational work has highlighted the relevance of the tumor microenvironment and recurrent genomic alterations such as BAP1, NF2, and CDKN2A in shaping immune activity and potentially modulating response to immune checkpoint inhibitors. Transcriptomic signatures and circulating biomarkers—including soluble mesothelin-related peptide—have shown prognostic associations but no validated predictive value. Overall, current evidence suggests that sensitivity to immunotherapy in MPM arises from a complex interplay of genomic, immunologic, and clinical factors, and that no biomarker is yet suitable for guiding treatment decisions. Prospective studies integrating molecular and immune profiling will be essential to refine patient selection and advance toward a more rationally personalized use of immunotherapy Full article

Background: Sigmoid volvulus is a time-critical cause of large-bowel obstruction. While endoscopic detorsion (ED) is the primary intervention for rapid decompression and the assessment of mucosal viability, reported success, recurrence, and mortality rates vary significantly across the literature, complicating evidence-based clinical decision-making. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines (protocol submitted to PROSPERO). MEDLINE/PubMed and Embase were searched from inception to 20 October 2025, supplemented by manual reference screening. We included original prospective or retrospective studies (n ≥ 5) reporting outcomes after ED for sigmoid volvulus, specifically technical success, post-ED recurrence, or mortality. Pooled proportions were estimated using a DerSimonian–Laird random-effects model on the logit scale, with heterogeneity quantified using I² statistics. Administrative database studies were summarized descriptively and excluded from the quantitative synthesis to minimize selection bias. Results: Nineteen studies (2004–2025) met the inclusion criteria from an initial 890 records. Fifteen studies (n = 1738) contributed to the analysis of technical success, yielding a pooled estimate of 80.0% (95% CI: 75.0–83.0%; I² = 87.5%). Seventeen studies (n = 3285) reported recurrence following initially successful ED, with a pooled rate of 33.9% (95% CI: 19.5–52.1%; I² = 97.5%). Sixteen studies (n = 2790) reported mortality; the pooled estimate was 22.6% (95% CI: 18.7–26.4%; I² = 99.6%). This extreme heterogeneity likely reflects variations in patient comorbidities (case-mix) and differing outcome reporting windows rather than procedural risk in isolation. Conclusions: ED is an effective first-line stabilizing intervention for uncomplicated sigmoid volvulus; however, recurrence rates remain high, and outcome estimates exhibit significant heterogeneity. ED should be integrated within a structured clinical pathway that prioritizes standardized mucosal assessment, post-procedural decompression, and the timely planning of definitive management when feasible. Full article

Background: Multiple myeloma (MM) is a hematologic malignancy characterized by clonal plasma cell expansion and diverse genomic rearrangements, including immunoglobulin heavy chain (IGH) translocations. Although RNA sequencing enables the comprehensive detection of IGH-associated fusions, routine molecular monitoring remains limited, particularly in non-secretory MM (NSMM), which lacks measurable serologic markers. Methods: Here, we contracted an integrated system combining RNA sequencing (RNA-seq) and reverse transcription quantitative polymerase chain reaction (RT-qPCR) to identify and validate fusion gene-based molecular markers for minimal residual disease (MRD) monitoring. Results: The global fusion landscape was delineated by the sequencing analysis of bone marrow samples from 22 newly diagnosed patients with MM. A total of 362 fusion events were identified, of which 190 non-immunoglobulin fusions were selected for detailed characterization. Recurrent breakpoints were concentrated on chromosomes 1 and 19, and five recurrent fusions, DDX5::EEF1A1, OAZ1::KLF2, OAZ1::KLF16, PFKFB3::LINC02649, and PLXNB2::SCO2, were detected across nine patients. Functional enrichment analyses indicated the significant involvement of these genes in RNA splicing regulation, transcriptional misregulation in cancer-related pathways, and focal adhesion processes. Twenty-three fusion transcripts were validated using RT-PCR and Sanger sequencing, demonstrating high specificity for MM. Longitudinal monitoring revealed that the quantitative assessment of fusion transcript levels enabled earlier relapse detection than flow cytometry, including in NSMM, where conventional MRD tools are ineffective. Conclusions: These findings suggest that individualized fusion transcripts serve as robust molecular markers for MRD surveillance. The proposed RNA-seq–RT-qPCR pipeline offers a clinically practical strategy to enhance precision diagnosis and personalized treatment in MM. Full article

Tailings dams represent one of the most environmentally sensitive infrastructures in the mining industry. To address the need for continuous and accurate monitoring, this paper presents an adaptive forecasting framework that combines Internet of Things (IoT) technologies with machine learning (ML) models to detect early signs of structural and ecological risks. The proposed system architecture is modular and scalable and enables the automated training, selection, and deployment of predictive models for multivariate sensor data. Each sensor data flow is independently analyzed by using a configurable set of algorithms (including linear, convolutional, recurrent, and residual models). The framework is deployed via containers with a CI/CD pipeline and includes real-time visualization through Grafana dashboards. A use case involving tiltmeters and piezometers in an operational tailing dam shows the system’s high predictive accuracy, with mean relative errors below $4\%$ across all variables (in fact, many of them have a mean relative error below $1\%$). These results highlight the potential of the proposed solution to improve structural and environmental safety in mining operations. Full article

Boron neutron capture therapy (BNCT) is experiencing a global resurgence driven by advances in boron pharmacology, accelerator-based neutron sources, and molecular imaging-guided theranostics. BNCT produces high linear energy transfer particles with micrometer-range energy deposition, enabling cell-selective irradiation confined to boron-enriched tumor cells in a geometrically targeted region by the neutron beam. This mechanism offers the potential for exceptionally high therapeutic ratios, provided two core requirements are met: sufficient differential tumor uptake of ¹⁰B and a neutron beam with appropriate energy and penetration. After early clinical attempts in the mid-20th century were hindered by inadequate boron agents and reactor-based neutron beams, recent technological breakthroughs have made BNCT clinically viable. The development of hospital-compatible accelerator neutron sources, next-generation boron delivery systems (such as receptor-targeted compounds and nanoparticles), advanced theranostic approaches (such as ¹⁸F-BPA positron emission tomography and boron-sensitive magnetic resonance imaging), and AI-driven biodistribution modeling now support personalized treatment planning and patient selection. These innovations have catalyzed modern clinical implementation, exemplified by Japan’s regulatory approval of BNCT for recurrent head and neck cancer and the rapid expansion of clinical programs across Asia, Europe, and South America. Building on these foundations, BNCT has transitioned from a predominantly academic experimental modality into an increasingly commercialized and industrially supported therapeutic platform. The emergence of dedicated BNCT companies, international collaborations between accelerator manufacturers and hospitals, and pharmaceutical development pipelines for next-generation boron carriers has accelerated clinical translation. Moreover, BNCT now occupies a unique position among radiation modalities due to its hybrid nature, namely combining the biological targeting of radiopharmaceutical therapy with the external-beam controllability of radiotherapy, thereby offering new therapeutic opportunities where competitive approaches fall short. Emerging evidence suggests therapeutic promise in glioblastoma, recurrent head and neck cancers, melanoma, meningioma, lung cancer, sarcomas, and other difficult-to-treat malignancies. Looking ahead, continued innovation in compact neutron source engineering, boron nanocarriers, multimodal theranostics, microdosimetry-guided treatment planning, and combination strategies with systemic therapies such as immunotherapy will be essential for optimizing outcomes. Together, these converging developments position BNCT as a biologically targeted and potentially transformative modality in the era of precision oncology. Full article

Cervical cancer is strongly associated with persistent infection by high-risk human papillomavirus (HPV). Recent advances in immunotherapy have redefined the therapeutic landscape of this disease. We aim to review the biological rationale, clinical evidence, and biomarker standardization supporting the use of immune checkpoint inhibitors (ICIs) in cervical cancer. A comprehensive review of recent literature and pivotal phase II–III clinical trials was performed, focusing on the PD-1/PD-L1 and CTLA-4 pathways, mechanisms of immune evasion, and predictive biomarkers. Persistent HPV infection leads to immune dysregulation and PD-L1 upregulation through E6/E7-mediated activation of the PI3K/AKT/mTOR and JAK/STAT pathways. ICIs have demonstrated significant improvements in overall survival, progression-free survival, and objective response rates in advanced and recurrent disease. PD-L1 immunohistochemistry using standardized assays such as 22C3 pharmDx and SP263 remains the key biomarker for treatment selection, while emerging molecular markers (TMB, MSI, HLA-I expression) are under investigation. Immunotherapy represents a major step forward in cervical cancer management, integrating molecular diagnostics and immune modulation into clinical practice. Continued efforts to refine biomarkers, optimize combination strategies, and expand global access will be essential to achieve equitable outcomes and disease elimination goals. Full article

Background/Objectives: Hybrid breast reconstruction (HBR), which combines implant-based reconstruction with autologous fat grafting (lipofilling), has emerged as a promising approach for improving both aesthetic and functional outcomes following mastectomy. This study aimed to evaluate patient-reported outcomes using the BREAST-Q questionnaire before and after lipofilling, focusing on aesthetic satisfaction, physical well-being, and quality of care. Methods: This before–after study included patients who underwent prepectoral implant-based reconstruction followed by one session of lipofilling between November 2024 and May 2025. The BREAST-Q questionnaire was administered preoperatively and at three months postoperatively. Statistical analyses were conducted to compare changes across aesthetic, functional, and care-related domains. Results: A total of 96 patients completed both pre- and postoperative questionnaires. Statistically significant improvements (p < 0.01) were observed in most aesthetic and psychosocial parameters, including satisfaction with breast appearance (Q1), psychosocial well-being (Q2), sexual well-being (Q4), and satisfaction with surgical outcomes (Q5). Physical symptoms such as discomfort (Q3) decreased significantly postoperatively. Satisfaction with medical care remained high, with minor improvements noted. No oncologic recurrences were reported. Conclusions: Hybrid breast reconstruction using fat grafting after implant placement offers significant benefits in terms of aesthetics, symptom relief, and patient satisfaction. It is a safe and effective procedure that can be widely integrated into clinical practice, provided that patient selection and technique are carefully considered. Full article