Search Results (1,331)

Insomnia is one of the most commonly reported challenges among cancer patients and survivors. Cognitive-behavioral therapy for insomnia (CBT-I) is an effective treatment but remains underused in routine cancer care. A stepped-care CBT-I program was developed to address this gap. This study explores facilitators and barriers following the implementation of this program in four Québec cancer centers. Patients and providers participated in two individual interviews and seven focus groups. Interviews were guided by the Consolidated Framework for Implementation Research (CFIR). Data were transcribed and coded in NVivo using the CFIR codebook. A hybrid deductive–inductive thematic analysis was conducted. Codes were interpreted using Proctor’s Implementation Outcomes Framework. A total of 14 patients and 18 providers were interviewed. Facilitators and barriers were divided into four key themes: (1) endorsement from trusted professionals; (2) fit with workflows and existing routines; (3) perceived burden for both patients and providers; and (4) readiness and motivation of both patients and providers. This analysis supports the acceptability, adoption, appropriateness, feasibility, and perceived sustainability of a stepped-care CBT-I in routine cancer care and suggests specific implementation strategies to optimize its implementation. Implementation of stepped-care CBT-I in routine cancer care has the potential to improve access to evidence-based treatments for insomnia and make it a standard component of survivorship care. Full article

Background: Mutations of the FLT3 gene, particularly internal tandem duplication (FLT3-ITD), define a biologically aggressive AML subtype with historically poor outcomes. Here we retrospectively assessed the clinical performance and tolerability of sorafenib with venetoclax plus azacitidine (VA) as front-line therapy in patients with newly diagnosed FLT3-ITD-mutated AML. Methods: Forty-five consecutive patients who received sorafenib plus VA induction were retrospectively analyzed. Post-remission therapy comprised sorafenib-based chemotherapy consolidation, continued sorafenib-VA, or allogeneic hematopoietic stem cell transplantation (allo-HSCT) after consolidation therapy according to clinical indication and guidelines. Composite complete remission (CRc), measurable residual disease (MRD), overall survival (OS), and relapse-free survival (RFS) were assessed. Results: The CR/CRi rate was 95.6% (43/45), and the FCM-MRD negativity rate after induction was 90.7%. At a median follow-up of 20.3 months, the 2-year OS and RFS of the entire cohort were 65.3% and 57.3%, respectively. The relapse rate in the patients receiving post-remission allo-HSCT after consolidation therapy was lower. Continued sorafenib-VA achieved a 2-year OS of 57.1% and a 2-year RFS of 64%. Multivariable analysis identified chemotherapy-based post-remission therapy (p = 0.016) and detectable MRD after the second consolidation cycle (p = 0.004) as independent adverse prognostic factors for RFS. No treatment-related mortality occurred. Conclusions: Sorafenib plus VA is a cost-effective, tolerable induction regimen achieving high remission and MRD negativity rates in FLT3-ITD-mutant AML. For transplant-eligible patients, allo-HSCT significantly improves long-term survival; for transplant-ineligible patients, continued sorafenib-VA yields sustained benefit. Full article

In this study, soy protein isolate, a renewable protein-based biopolymer containing a minor carbohydrate fraction, was formulated into a polymeric binder using polyvinyl alcohol (PVA) and oxidized glucose and applied to improve the hydro-mechanical behavior of collapsible soils. The resulting soy protein–PVA-based binder (CSP) was evaluated against chitosan through laboratory tests including collapse potential, unconfined compressive strength (UCS), consolidated drained triaxial testing, permeability, and microstructural characterization using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). CSP substantially improved the engineering performance of the treated soils. For Soil C, the collapse potential decreased from 9.3% for the untreated soil to 3.0% with only 0.25% CSP. At 1.5% CSP and 9 days of curing, the UCS reached 2367 kPa for Soil C. In consolidated drained triaxial testing, the cohesion of soil C increased from 5 kPa in untreated soil to 734 kPa with 1% CSP, while the corresponding friction angle increased from 24° to 28°. FTIR and SEM observations indicated changes in the chemical environment and composite microstructure after treatment, although FTIR alone does not establish covalent crosslinking. Overall, the results demonstrate the potential of the CSP-based binder to improve the mechanical and collapse behavior of collapsible soils under the investigated laboratory conditions. Full article

Oral mucosal diseases often lead to structural damage and functional impairment due to high recurrence and malignant progression. Current therapeutic outcomes remain unsatisfactory owing to the complex oral microenvironment. Recent reviews have covered individual aspects of oral mucosal drug delivery, such as bioactive materials, mucoadhesive systems, and nanocarriers, but few have considered all four interrelated dimensions, including saliva-mediated adhesive barriers, epithelial permeability, biomechanical adaptability, and translational bottlenecks, in an integrated manner. The present review offers an attempt to consolidate these dimensions into one framework, aiming to provide readers with a more comprehensive perspective on the challenges inherent in this field. To underpin this framework, we conducted a structured literature search covering Web of Science (2015–2026), with predefined inclusion/exclusion criteria, followed by thematic synthesis. We first summarize the clinicopathological features and current treatment landscape of major oral mucosal diseases. We then dissect three critical barriers to transmucosal delivery: adhesive interference by salivary flow, epithelial tight junction resistance, and dynamic biomechanical forces (e.g., chewing, tongue movement). Drawing on saliva and mucosa interfacial physics, we rationalize the need for wet-adhesive material design and survey diverse mucoadhesive polymers and formulations, detailing their binding mechanisms. For epithelial penetration, we highlight design principles of microneedles and nanocarriers while critically discussing their dual-edged safety–efficacy profiles. To cope with the highly deformable oral biomechanical environment, we propose mechanical property matching and asymmetric structural designs. Finally, we outline key translational bottlenecks and future breakthroughs. This review offers an integrated, barrier-informed guide for next-generation oromucosal formulations. Full article

South Africa’s (SA) quadruple disease burden comprises communicable diseases such as HIV/AIDS, tuberculosis, maternal and child mortality, non-communicable diseases (NCDs), and injury and violence. Two of these components, HIV and NCDs, generate demand for long-term medicines and are the focus of the review. To improve access to chronic medicines and to alleviate the pressure on overburdened public health facilities, the National Department of Health launched the Central Chronic Medicines Dispensing and Distribution (CCMDD) programme. Stable, compliant patients were granted access to patient medicine parcels (PMPs) via decentralised community pick-up points (PUPs), thereby reducing clinic congestion and improving patient convenience. Despite considerable scale-up, implementation has been inconsistent among provinces. While regional syntheses of differentiated service delivery models exist, no synthesis has yet consolidated the barriers and facilitators specific to the CCMDD across the full decade of its implementation. To understand the barriers and facilitators, a scoping review was conducted for studies published in English between 2014 and 2024. The search was filtered primarily for duplicates, then title and abstract screening, of which 31 articles met the inclusion and exclusion criteria. Data were analysed using inductive thematic analysis; resulting themes were subsequently mapped to the Consolidated Framework for Implementation Research (CFIR) to contextualise findings within implementation science. A grey literature search was also conducted through Google Scholar and Sabinet. Key facilitators of implementation included decentralised service delivery and community-based distribution, reduced patient waiting times, enhanced treatment adherence, reduced patient-borne transport and time costs and improved access to medicines. Limited access to pick-up points in remote areas, miscommunication regarding pick-up dates and poor staff service were cited as barriers. The findings revealed a gap between planned activities and implementation and have significant implications for policy and practice. It further highlighted the need for ongoing optimisation strategies to enhance the programme. Full article

This study investigated the synthesis and microstructural evolution of AlFeCoNi medium-entropy alloy powder processed by ball milling, conventional uniaxial pressing, and vacuum sintering at 900 °C for 1 h. The mechanically milled powder exhibited a refined, irregular particle morphology with a broad size distribution, indicating extensive fracture and cold-welding during milling. SEM (scanning electron microscopy) and EDS (energy-dispersive spectroscopy) observations showed effective elemental mixing of Al, Fe, Co, and Ni, with only limited evidence of large-scale segregation, suggesting that mechanical alloying promoted compositional homogenization. After compaction and sintering, the powder compact exhibited noticeable changes in microstructural continuity and pore morphology, indicating further microstructural evolution during thermal treatment. Overall, the results demonstrate the microstructural evolution of AlFeCoNi MEA during ball milling and subsequent conventional sintering, while further investigation involving quantitative densification measurements and optimization of sintering conditions is required to establish the consolidation behavior and microstructural uniformity of the alloy. Full article

Background/Objectives: Stone composition reflects the urinary environment in which calculi form, whereas 24 h urine testing identifies modifiable lithogenic abnormalities. This study examined component-specific urinary metabolic profiles and evaluated whether routine clinical and urinary variables could distinguish common stone minerals. Methods: This retrospective study included 256 patients undergoing 297 stone surgeries, consolidated into 256 treatment episodes. Fourier-transform infrared spectroscopy identified stone minerals, which were linked to preoperative 24 h urine profiles. Calcium oxalate monohydrate (COM), calcium oxalate dihydrate (COD), carbonate apatite, and anhydrous uric acid were evaluated using multivariable logistic regression. Mutually exclusive calcium oxalate–calcium phosphate phenotypes, nested cross-validated prediction models, and unsupervised clustering were also examined. Results: COM, COD, carbonate apatite, and anhydrous uric acid were present in 78.5%, 73.0%, 39.5%, and 9.8% of episodes, respectively. Higher urine pH was associated with carbonate apatite (odds ratio [OR] per standard deviation, 1.78; 95% confidence interval [CI], 1.33–2.38), whereas lower pH was associated with anhydrous uric acid (OR, 0.26; 95% CI, 0.11–0.58). Higher urinary citrate was associated with COM, but phenotype analysis showed that hypocitraturia increased from 45.3% in calcium oxalate-only episodes to 60.7% in mixed calcium oxalate–calcium phosphate episodes and 89.5% in calcium phosphate episodes without calcium oxalate. Lower urine volume was associated with COD. Cross-validated areas under the curve ranged from 0.654 to 0.712, and metabolic clusters showed substantial mineral overlap. Conclusions: Urine pH provided the clearest component-specific signal, whereas citrate associations depended on accompanying minerals. Routine 24 h urine testing complemented but did not replace direct stone analysis. Full article

Introduction: Inflammatory bowel disease (IBD) is an umbrella term encompassing two major chronic immune-mediated disorders, Crohn’s disease (CD) and ulcerative colitis (UC). Its pathogenesis reflects complex interactions among genetic, microbial, metabolic, environmental, and immune factors. Growing evidence supports the concept of IBD as a systemic disease associated with intestinal dysbiosis, epithelial barrier dysfunction, metabolic alterations, and extraintestinal complications. However, these interconnected mechanisms and their systemic consequences are often examined separately, limiting an integrated understanding of IBD and its implications for individualized management. Accordingly, an updated synthesis linking intestinal, microbial, metabolic, immune, and systemic processes is needed to consolidate current evidence and support precision medicine. Methods: A narrative literature review was conducted using PubMed, Web of Science, and LILACS. The search strategy used controlled vocabulary terms indexed in Medical Subject Headings (MeSH) and Health Sciences Descriptors (DeCS), combined with Boolean operators. Studies addressing IBD epidemiology, pathophysiology, clinical manifestations, diagnosis, treatment, gut microbiota, microbial metabolites, and systemic complications were critically evaluated. Results: Current evidence indicates that dysbiosis and impaired intestinal barrier integrity are associated with alterations in microbial metabolites, including short-chain fatty acids, bile acids, lipids, and other microbiota-derived compounds. These alterations interact with immune and inflammatory pathways and may contribute to extraintestinal manifestations, particularly metabolic and hepatobiliary disorders through the gut–liver axis. Advances in metabolomics, multi-omics approaches, biologic agents, and targeted therapies are expanding opportunities for patient stratification and individualized treatment. Conclusions: IBD should be regarded as a systemic and multifactorial disorder involving interconnected microbial, metabolic, molecular, and immune mechanisms. Integrating these dimensions may improve disease monitoring, therapeutic selection, and the development of precision medicine strategies. Full article

Shallow failure and surface erosion account for the majority of rainfall-induced slope damage on Korean expressways, yet conventional countermeasures such as anchors and soil nailing are designed against deep-seated circular failure. This study evaluates the erosion resistance and slope-scale performance of a cement-free surface stabilizer composed of ground granulated blast furnace slag and hemihydrate gypsum as binders, with high-calcium fly ash, magnesium sulfate and a nutrient additive. Two selected mixes for water contents above and below 30%, C-91-6.41-30 and C-94-4.276-25, were examined; at the total agent content specified in the applicable construction specification, their binder contents were 28.8% and 28.7% lower, respectively. Consolidated drained direct shear tests at 3 days of curing gave cohesion increases of 160% and 65.6% over the parent soil, with the friction angle increasing by 71% in the former and by only 0.3% in the latter, indicating a cohesion-dominated improvement at the lower water content. Under simulated rainfall of 30 mm/h for 60 min, the parent soil lost 70.92–77.39% of its mass and failed by sliding, whereas the improved slopes lost only 0.23–1.27%, a reduction of 98.2–99.7%, with only localized surface erosion and no progression to global sliding. Coupled transient seepage and limit-equilibrium analyses were conducted for the geometry and stratigraphy of an actual failed slope under a conservative upper-bound infiltration scenario. The maximum hourly rainfall intensity recorded on each day during the antecedent rainfall period was applied as a sustained 24 h surface flux to impose a severe hydraulic loading condition. Under this assumption, 0.5 m improved layers gave factors of safety of 1.416 and 1.475, compared with 0.759 for the unreinforced section. A closed-form check at the field stress level shows that 85–93% of the mobilized shear resistance of the improved layer is contributed by cohesion, indicating that the calculated shear-strength improvement at this stress level is predominantly attributable to the cohesion component rather than the high apparent friction angle. The numerical analysis was subject to limitations associated with differences between the laboratory parent soil and the field soil, the limited hydraulic characterization of the improved layer, the simplified treatment of surface runoff, and the artificial upper-bound rainfall boundary condition. Therefore, the numerical results should be interpreted as a comparative parametric evaluation of the mechanical contribution of surface stabilization under severe infiltration conditions rather than as a reproduction of an observed rainfall event or a prediction of the actual failure timing. Full article

Background: Spinal cord stimulation (SCS) is an established therapy for chronic neuropathic pain, yet a substantial minority of implanted patients do not obtain durable relief, and patient selection still relies largely on a subjective percutaneous stimulation trial. Objective neurophysiological and psychophysical biomarkers could enable precision selection, but their predictive value has not been consolidated across modalities. Objectives: To evaluate whether pre-treatment or intraoperative neurophysiological (electroencephalography (EEG), magnetoencephalography (MEG), somatosensory evoked potentials (SSEP), evoked compound action potentials (ECAP)) and psychophysical (conditioned pain modulation (CPM), quantitative sensory testing [QST]) biomarkers predict SCS treatment response in adults with chronic neuropathic pain. Methods: Following a pre-registered protocol (International Prospective Register of Systematic Reviews (PROSPERO CRD420261410302)) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline, we searched six databases and two registries; the final search was run on 4 June 2026. Records underwent dual, independent screening in Rayyan; data were extracted in duplicate and risk of bias was assessed with the Quality In Prognosis Studies (QUIPS) tool, the Prediction model Risk Of Bias Assessment Tool (PROBAST), or the Quality Assessment of Prognostic Accuracy Studies (QUAPAS) tool. Because of clinical and methodological heterogeneity, findings were synthesized narratively using the Synthesis Without Meta-analysis (SWiM) guideline. Results: Twelve peer-reviewed studies met eligibility. Most were prognostic-factor or responder-discrimination studies rather than prospectively validated predictors; two were multivariable machine learning prediction models and one used ECAP-derived neural dose as a therapy-embedded surrogate. The strongest single-study signal was the preoperative SSEP (one 2003 cohort, n = 95), in which normal dorsal-column central conduction was associated with a 75% success rate; this legacy finding requires replication with contemporary SCS paradigms. Resting EEG/MEG spectral features (alpha, gamma) discriminated responders in several small cohorts. The two prediction models reported apparent internal accuracy of 76–88% (area under the curve up to 0.88) but neither underwent external validation. QST and CPM findings were promising but directionally inconsistent. All 12 studies were at high overall risk of bias. Conclusions: Objective biomarkers—most notably the preoperative SSEP and resting-state EEG/MEG spectral features—show promise for predicting SCS response, but the evidence is preliminary, heterogeneous, small, and lacks external validation. Adequately powered, prospective, externally validated studies are needed before clinical adoption. Full article

Phosphorus (P) limitation constrains crop production in highly weathered tropical soils, and microbial inoculants may enhance P acquisition, although their effectiveness varies with edaphic conditions. We hypothesized that the effects of a phosphate-solubilizing bacterial inoculant on plant performance and belowground processes would depend on soil P status and no-tillage history. A two-year field experiment on an Oxisol in the Brazilian Cerrado (Chapadão do Sul, MS, Brazil) compared newly established, low-P (NTS-NC) and consolidated, high-P (NTS-C) no-tillage systems. Treatments combined 0, 50, or 100% of recommended P fertilization with or without BiomaPhos^®, composed of Priestia megaterium CNPMS B119 and Bacillus subtilis CNPMS B2084. Grain yield, resin-extractable soil phosphorus (P-resin), root architecture, bacterial and arbuscular mycorrhizal fungal (AMF) communities, AMF colonization, and phosphatase activities were evaluated. Grain yield in NTS-C exceeded NTS-NC by 15.7% and 18.8% in 2021/2022 and 2022/2023, respectively. Inoculation × P interactions for yield and P-resin occurred only in NTS-NC in the second season. Inoculation altered root architecture, whereas P availability reorganized bacterial association networks. AMF responses were limited and season-specific, while inoculation reduced AMF colonization and phosphatase activity primarily in NTS-C. These findings confirm that inoculant performance is context-dependent and should be integrated with site-specific P fertilization strategies. Full article

Unresectable locally advanced non-small cell lung cancer (LA-NSCLC) remains a therapeutic challenge, despite the paradigm shift established by the PACIFIC trial (concurrent chemoradiation followed by Durvalumab consolidation). A substantial number of patients still experience disease progression and significant toxicity. This narrative review explores innovative radiation therapy (RT) strategies and their integration with systemic therapy. Key innovations analyzed include: 1. Systemic Therapy Intensification: Induction chemo-immunotherapy or novel multi-agent consolidation regimens show promise, but managing increased toxicity remains critical. The integration of DNA damage response inhibitors with RT is also being actively explored to maximize radiosensitization. 2. RT Dose and Volume Modulation: Recent data suggests that dose escalation via highly conformal hypofractionation or stereotactic ablative body radiotherapy (SABR) may enhance efficacy, particularly when combined with immunotherapy. Conversely, risk-adapted de-escalation of dose or volumes is studied to reduce immunosuppression and treatment-related toxicity, allowing more patients, including the elderly and frail, to complete consolidation. 3. Organ-at-Risk (OAR) Sparing: Advanced techniques like intensity-modulated radiation therapy (IMRT), adaptive RT (ART), and proton beam therapy (PBT) are crucial for minimizing dose to OARs and new substructures, such as specific cardiac subregions and lymphoid tissues. This OAR sparing is strongly correlated with improved OS and reduced immunosuppression. In conclusion, this narrative review focuses on the future of LA-NSCLC treatment, which is moving toward personalized, precision RT, embracing both intensification and thoughtful de-escalation, supported by synergistic systemic agents, to maximize curative potential and minimize toxicity. Full article

Osteoarthritis (OA) is a joint disease of unknown etiology that can occur in joints throughout the body, especially with articular cartilage lesions of the knee joint and hip joint. Osteoarthritis not only causes joint pain, deformity, and functional impairment, but also significantly increases the risk of cardiovascular events, deep vein thrombosis in the lower limbs, and hip fractures. Up to now, there have been no specific medications available for the treatment of osteoarthritis, and the disease remains incurable. Therefore, identifying reliable biomarkers is crucial for achieving a more accurate diagnosis of OA and for guiding the development of targeted treatment strategies. In this paper, we screen and synthesize articles that performed transcriptomics and proteomics analysis on tissue or cell samples taken from osteoarthritis cartilage. We identify common differentially expressed genes (co-DEGs) and proteins (co-DEPs) in cartilage samples from knee osteoarthritis (KOA) and hip osteoarthritis (HOA) and consolidate them into candidate molecules, while systematically delineating their expression trends and underlying mechanisms at both the transcriptomic and proteomic levels. This review establishes a theoretical foundation and identifies future research directions for functional validation and clinical translation of these candidate molecules as potential biomarkers and therapeutic targets for osteoarthritis. Full article

Pleomorphism in cells encompasses a variety of morphological features, such as heterogeneity in the size and shape of cells and nuclei, irregularity of the nuclear membrane, hyperchromasia, and peculiarities of cell organelles. Pleomorphism in mammalian cells is associated with genetically unstable neoplasms and is frequently accompanied by high rates of proliferation and low differentiation status. Among soft tissue sarcomas, a group of tumors characterized by the pleomorphic phenotype can be distinguished. Pleomorphic soft tissue sarcomas are a rare, understudied group of soft tissue sarcomas with aggressive behavior, low survival rates, and high resistance to standard chemotherapy treatment. Knowledge of the mechanisms behind the pleomorphic features, common genetic and epigenetic alterations, and their association with aggressive tumorigenesis is essential for advancing patient care for this group of sarcomas. In this narrative review, we consolidate existing evidence concerning clinical features of pleomorphic sarcomas, their possible histogenesis, the common drivers and transcriptional networks, and the potentially available approaches for treatment. Full article

Benign paroxysmal positional vertigo (BPPV) is the most common cause of patient-reported vertigo. The accurate diagnosis of BPPV requires high-quality physician training and knowledge of the advantages and disadvantages of different diagnostic methods. Most studies focus on a limited number of diagnostic approaches; the purpose of this review is to consolidate and systematize the available information on the wide range of existing methods. This review includes comparative descriptions of the clinical utility of 12 different techniques used to diagnose BPPV. The diagnosis of BPPV relies primarily on a thorough analysis of clinical history and the professional application of positional tests (primarily the Dix–Hallpike and the Pagnini–McClure maneuvers). Several methods can be used to enhance the efficiency of positional testing: rotary chair, electronystagmography (ENG), videonystagmography (VNG), and potentially artificial neural networks for the analysis of VNG results. The VEMP (vestibular evoked myogenic potential) technique, vestibular caloric testing, the video head impulse test, computerized posturography, and CT and MRI of the head are all useful auxiliary methods for the differential diagnosis of BPPV in complex cases. When selecting diagnostic approaches, it is important to consider the balance between resource and time expenditure and diagnostic accuracy. This review enables a comprehensive and well-rounded understanding of a wide range of diagnostic methods, which is necessary for the development of optimal diagnostic and subsequent treatment and monitoring tactics. Full article