Search Results (2,325)

Endometrial carcinoma (EC) with choriocarcinomatous differentiation is an exceptionally rare malignancy for which standardized postoperative treatment strategies are lacking. Herein, we describe two postmenopausal patients with endometrioid carcinoma containing a choriocarcinomatous component. One patient had an EC-dominant tumor with low and rapidly normalized postoperative serum human chorionic gonadotropin (hCG) levels and received paclitaxel plus carboplatin. The other patient had a choriocarcinomatous-dominant tumor with markedly elevated postoperative serum hCG levels and was treated with gestational trophoblastic neoplasia (GTN)-oriented chemotherapy using etoposide, methotrexate, actinomycin D/cyclophosphamide, and vincristine (EMA/CO). Both patients remain disease-free. A review of representative published cases revealed two competing treatment paradigms, EC-oriented and GTN-oriented, applied inconsistently and without unified selection criteria. On the basis of integrated clinicopathological assessment, we propose that postoperative treatment consideration should be guided primarily by dominant tumor biology, rather than the International Federation of Gynecology and Obstetrics stage alone. Tumors with a dominant choriocarcinomatous component accompanied by elevated postoperative serum hCG levels may benefit from GTN-oriented chemotherapy, whereas EC-dominant tumors with low or normalized hCG levels may benefit from EC-oriented regimens. Reassessment of dominant tumor biology using postoperative pathological findings and serum hCG dynamics may provide a pragmatic, decision-support framework for adjuvant treatment consideration in this rare and clinically challenging entity. Full article

Background: Blood flow restriction (BFR) training induces morphological and neuromuscular adaptations using low-intensity exercise (20–40% 1RM), offering a reduced mechanical load alternative to traditional high-load resistance training. Safe and effective implementation, however, requires a clear understanding of physiological mechanisms, contraindications, and pressure determination methodologies. In this three-part series, we provide a comprehensive review of BFR for athletic populations and provide strength and conditioning coaches with a structured framework for screening, safety, and methodological considerations to support BFR integration in high-performance settings. Methods: A narrative review of the literature examining BFR safety, contraindication screening, adverse event reporting, and occlusion pressure determination was conducted using a PubMed and MEDLINE search. Search terms included combinations of (“blood flow restriction” OR “BFR” OR “occlusion training” OR “KAATSU”) AND (“safety” OR “contraindications” OR “risk stratification”) AND (“arterial occlusion pressure” OR “limb occlusion pressure” OR “occlusion pressure” OR “Doppler” OR “handheld Doppler” OR “pulse oximetry” OR “cuff width” OR “capillary refill time” OR “monitoring”). Studies examining contraindication screening systems, arterial occlusion pressure calculation methods, and real-time monitoring protocols were evaluated. Primary considerations included risk stratification frameworks, pressure determination accuracy, and control parameter validation for ensuring vascular safety during application. Results: Risk stratification systems can effectively identify absolute and relative contraindications requiring medical clearance prior to BFR use. Epidemiological data indicate that adverse events are transient and non-serious, while serious events appear rare when evidence-informed protocols are applied. Doppler-based assessment remains a criterion approach for determining inflation pressure, although validated estimation methods using limb circumference and systolic blood pressure offer a pragmatic and comparable alternative for applied environments. Inflation pressures of 50–80% arterial occlusion, adjusted for cuff width, produce effective and safe stimulus. Real-time monitoring through capillary refill time, pulse strength palpation, and skin coloration can support iterative pressure optimization and help identify excessive restriction pressures. Conclusions: BFR implementation in athletic populations requires systematic screening protocols, individualized inflation pressure determination using validated methods, and real-time monitoring parameters. These foundations provide the essential safety infrastructure required before progressing to specific training applications across resistance, cardiovascular, and other performance and rehabilitation modalities. Full article

The global construction industry urgently requires sustainable alternatives to ordinary Portland cement (OPC) to mitigate its immense carbon footprint. Red mud (RM), a highly alkaline bauxite residue, presents tremendous but challenging potential as a supplementary cementitious material. This review systematically bridges the gap between atomic-level interfacial bonding mechanisms and macroscopic engineering performance, highlighting how these properties are significantly dictated by specific RM sources (e.g., Bayer vs. Sintering processes). We first elucidate advanced pretreatment strategies, notably CO₂ mineralization, which synergistically mitigates extreme alkalinity and sequesters carbon. Crucially, the fundamental bonding mechanisms are decoded: beyond physical filling, RM integration induces significant micro-morphological densification via intense aluminosilicate depolymerization—evidenced by the Al[VI] to Al[IV] coordination shift—and the quantitative integration of approximately 40% reactive iron phases into stable Fe-S-H networks. By clearly distinguishing between traditional hydration and clinker-free alkali-activation pathways, we evaluate holistic structural parameters beyond mere 28-day compressive strength (40–67 MPa), explicitly addressing flexural capacity, modulus of elasticity, and volume stability. Environmental assessments confirm exceptional heavy metal immobilization (>95% efficiency, leaching < 0.010 mg/L) and a substantial 50–80% reduction in Global Warming Potential (GWP), provided the environmental burden of alkaline activators is rigorously accounted for. Furthermore, the long-term risk of Alkali–Silica Reaction (ASR) is evaluated as a primary durability concern. Finally, to overcome persistent rheological bottlenecks, this paper highlights transformative future trajectories, particularly data-driven Machine Learning (ML) for complex mix optimization and 3D concrete printing for advanced infrastructure. Ultimately, this review provides a robust theoretical foundation and a pragmatic roadmap for upcycling RM into safe, high-performance, and ultra-low-carbon building materials. Full article

Emery–Dreifuss muscular dystrophy (EDMD) is a rare inherited neuromuscular disorder within the spectrum of nuclear envelope diseases, classically characterized by early musculo-tendinous contractures, slowly progressive myopathy, and cardiac involvement dominated by conduction disease and arrhythmias, with variable evolution toward cardiomyopathy and heart failure. This narrative review provides a comprehensive and clinically actionable synthesis of cardiovascular manifestations across EDMD genotypes and phenotypes, outlining pragmatic diagnostic and therapeutic pathways for real-world care. A targeted literature search was performed in PubMed, Embase, and Web of Science, focusing on studies addressing cardiovascular involvement in EDMD. Relevant original studies, case series, registries, guideline documents, and high-quality reviews were selected and synthesized narratively, with particular emphasis on diagnostic strategies, risk stratification, and management approaches. Cardiac involvement in EDMD encompasses a broad and heterogeneous spectrum, including atrial disease and conduction disturbances, ventricular arrhythmias, dilated cardiomyopathy, thromboembolic complications, and sudden cardiac death. Phenotypic expression varies according to the underlying genetic substrate, with distinct atrial- and ventricular-dominant trajectories. Early recognition and structured cardiovascular surveillance are essential to guide timely intervention, including anticoagulation, device therapy, and heart failure management. Despite growing awareness, significant gaps remain in risk prediction and standardized management strategies. EDMD represents a paradigmatic model of cardiomyopathy characterized by prominent electrical instability and systemic involvement. A structured, genotype- and phenotype-informed approach centered on early surveillance, proactive arrhythmia and thromboembolic risk management and timely device therapy may improve clinical decision-making in real-world settings. Future perspectives include the integration of precision medicine and the development of gene- and pathway-targeted therapies, with the potential to shift from symptomatic management toward disease-modifying strategies. Full article

Dysregulated iron handling—including catalytic iron and ferroptosis, hepcidin–ferroportin signaling, ferritin dynamics, and neutrophil gelatinase-associated lipocalin (NGAL)-mediated siderophore transport—has been implicated in the initiation and propagation of acute kidney injury (AKI) across ischemia–reperfusion, sepsis, and nephrotoxic contexts. To provide a SANRA-aligned narrative synthesis of mechanistic and translational evidence on iron biology in AKI, clarifying biomarker readiness and therapeutic prospects while explicitly separating preclinical from human findings. PubMed, Scopus, and Web of Science (1 January 2000 to 30 September 2025), plus appraised grey literature (guidelines/registries) using predefined criteria (authority, update recency, and methodological transparency). Narrative review with comprehensive database searches, single-reviewer screening/extraction (acknowledged as a limitation), and qualitative synthesis. Evidence is organized by pathway (catalytic iron/ferroptosis, transferrin (Tf)/transferrin receptor (/TfR), ferritin/ferritin heavy chain (FtH), hepcidin–ferroportin and NGAL) and translational domain (biomarkers and therapeutics). Statements are tagged as [Preclinical] or [Human]. [Preclinical] Robust signals support roles for catalytic iron and ferroptosis, protection by iron chelation, hepcidin modulation, heme oxygenase 1 (HO-1)/FtH induction, and apotransferrin/NGAL-based strategies. [Human] Biomarkers such as NGAL show clinical utility for kidney injury detection, whereas catalytic iron assays (labile plasma iron [LPI]/bleomycin-detectable iron [BDI]) remain investigational with limited standardization. Observational links between iron-regulatory pathways and AKI risk exist, but interventional trials are sparse; dose, timing, and safety of iron-targeted strategies in defined AKI settings remain to be established. Iron-handling pathways are compelling targets for AKI prevention/mitigation, yet high-quality human trials are limited. Priorities include standardized catalytic-iron assays, biomarker-guided enrichment, and pragmatic trials of tractable interventions (e.g., peri-contrast or cardiopulmonary bypass settings). Until such evidence accumulates, recommendations beyond standard care should be avoided. Full article

Reconciling environmental conservation with socioeconomic development remains a fundamental challenge for tropical forest governance. Thirty-five years ago, the Brazilian Amazon pioneered Extractive Reserves (RESEXs) as a radical model for socio-environmental synergy; however, their long-term efficacy faces increasing contestation. Through a systematic review of three and a half decades of research, we analyze the RESEX model’s performance in balancing forest integrity with the livelihoods of traditional communities. Our synthesis reveals a persistent conservation–development misalignment, where the prioritization of ecological preservation is coupled with chronic underinvestment in socioeconomic infrastructure. We demonstrate that this imbalance has yielded a “vulnerability trap,” where stagnant agro-extractive initiatives and insufficient technological integration inadvertently push local populations toward predatory land-use alternatives. We argue that prioritizing forest cover metrics while neglecting the economic agency of traditional populations constitutes an inadequate strategy for the Amazon’s future. Following the outcomes of the 30th Conference of the Parties (COP30) in Belém, we propose a paradigm shift toward a technologically enabled bioeconomy—a move essential for the pragmatic success of global climate goals and the protection of the Amazonian climate anchor. Full article

Background: Communication, language, and speech disorders are highly prevalent in children with cerebral palsy (CP) and substantially impact social, educational, and community participation. However, few studies have systematically characterized communicative and linguistic profiles using standardized assessments. This paper outlines the work of the ‘Italian CP & Language Network’ over the last two years, focusing on identifying research priorities, developing specialized assessment protocols, and proposing a shared classification system for speech and language disorders in children with CP. Methods: A survey was sent to 11 specialized centers to investigate clinical practices and assessment tools. Based on the results and an extensive literature review, the group developed three age- and complexity-based diagnostic protocols and a shared classification system. Results: The survey highlighted high variability in test selection, especially for speech and pragmatic assessment, and a significant need for ad hoc tools for augmentative and alternative communication (AAC). Three standardized protocols were defined: (1) early language (<48 months), (2) school-age language and pragmatics (4–12 years), and (3) minimally verbal children (6–12 years). A multi-level classification system for language and speech disorders was proposed to improve diagnostic consistency. Conclusions: Standardizing assessment is a critical step toward early identification of communicative vulnerabilities to guide tailored interventions and promote participation and quality of life across developmental stages. The group provides a framework for prospective multicenter data collection to correlate linguistic and speech phenotypes with neuroradiological features and motor outcomes. Full article

Concurrent/interleaved transcranial magnetic stimulation combined with functional MRI (TMS–fMRI) enables causal perturbation of targeted cortical regions while measuring whole-brain MR-based responses during stimulation. This perspective argues that the main translational value of concurrent/interleaved TMS–fMRI lies in operationalizing target engagement and network-level propagation as measurable endpoints, bridging stimulation “dose” to clinically meaningful effects. Rather than proposing a validated gold-standard protocol, we frame concurrent/interleaved TMS–fMRI as a measurement-driven translational approach in which MRI-informed targeting and MR-based readouts can be integrated to quantify target engagement under clearly specified methodological and quality-control conditions. This perspective specifically aims to make explicit an intermediate verification step that remains only partially formalized in current clinical neuromodulation workflows. We propose that MRI-based neuronavigation should move beyond template coordinates toward individualized anatomical and network-informed targeting, with the aim of improving precision, reproducibility, and safety. Building on the field’s evolution from technical feasibility to emerging clinical applications, we outline a staged framework from feasibility to biomarker potential, summarize representative protocol archetypes, and provide pragmatic recommendations for reporting and study design to improve comparability. This framework is intended to guide future concurrent/interleaved TMS–fMRI studies toward biomarker-ready designs and more clinically informative network neuromodulation. We further distinguish offline MRI-informed targeting from potential future real-time or closed-loop implementations, and we emphasize that current biomarker claims should remain proportional to the still heterogeneous evidence base. Full article

Natural resource management and area-based conservation are increasingly recognised as outcomes of complex interactions between ecological conditions and social systems, shaped by local knowledge, governance arrangements, and environmental pressures. The Social-Ecological Systems Framework (SESF), developed by Elinor Ostrom, provides a comprehensive framework to analyse these dynamics; however, most applications remain context-specific, limiting cross-site comparability. This study introduces the Conservation and Human Use Index (CHUI), a standardised diagnostic tool that operationalizes SESF principles for comparative analysis across conservation-important areas. CHUI comprises 134 qualitative questions structured across four equally weighted dimensions: (i) Natural Values and Ecosystem Services, (ii) Threats and Pressures, (iii) Governance, and (iv) Social Perceptions. Using an ordinal 0–3 scale with a “Not Applicable” option, the Index enables consistent, flexible application through both desk-based assessments and participatory processes. It generates aggregate and disaggregated outputs that help identify pressure hotspots, governance gaps, and conservation-use synergies. CHUI’s primary innovation lies in translating SESF into a pragmatic and participatory instrument that supports real-world decision-making. Rather than replacing detailed ecological or socio-economic assessments, it functions as a collaborative diagnostic compass to guide targeted investigation and intervention. Its participatory design fosters shared learning, transparency, and co-production of context-specific management pathways, supporting adaptive stewardship and community empowerment. Developed within the Horizon Europe PRO-COAST project and tested across ten European coastal case studies, CHUI advances both the operationalization of SESF and the practice of inclusive, adaptive conservation management. Full article

This study addresses the critical challenge of translating the profound social, spatial, and cultural dynamics of the traditional introverted Persian house into more tangible design metrics for contemporary Iranian housing. Relying on qualitative data from twenty-four diverse expert interviews across architecture, urban planning, and policy, the research demonstrates a broad consensus that the notion of replicating historical form is unsustainable. Instead, it indicates that the introverted configuration is likely a context-specific ontological imperative—viewed here as a fundamental socio-spatial requirement—rooted in measurable performance, serving simultaneous social, cultural, psychological, and environmental paradigms. The main findings show that preserving cultural continuity requires a shift from aesthetic conservation to prescriptive configuration. This logic is synthesised into a consolidated socio-spatial framework, whose originality lies in introducing three regulatory design instruments: (1) the sequenced depth and filtration protocol for spatial arrangement; (2) the controlled visual and environmental parameters for façade performance; and (3) the cultural adaptability and resilience requirement for functional programming. The framework’s prescriptive metrics, such as minimum space syntax values and the visual filtering coefficient, provide regulatory bodies with the precise technical tools necessary to enforce cultural protocols like privacy and dignity in high-density urban developments. While these metrics serve as an operationally promising model, they represent a theoretical framework that requires further empirical validation in diverse contemporary residential settings before mandatory regulatory adoption. This framework offers a pragmatic pathway for safeguarding Iranian housing’s cultural identity, ensuring future developments are certified not only for safety and structure, but for their adherence to the fundamental socio-spatial contract of the Persian dwelling. Full article

In this article, we address the issue of the sometimes indeterminate grammatical and functional status of vocatives and vocative-like NPs by proposing a prototype-based approach to their classification. We then explore the socio-pragmatic functions of these vocative types, adopting a variationist perspective that considers both macro- and micro-social factors to determine when the different types of vocatives occur and how they contribute to managing interpersonal relationships. This exploratory analysis is based on data from an online questionnaire featuring Discourse Completion Tasks of over 3000 participants in Germany, Austria, and Switzerland. The findings show that different vocative types fulfill distinct socio-pragmatic functions, ranging from signaling positive politeness to heightening the face-threatening potential of an utterance, depending on the communicative task performed. In addition, their use varies between participants, based on the speakers’ regional background, gender, age, or personality traits. Full article

Background: Digital health has accelerated telehealth uptake, yet evidence comparing video-based musculoskeletal assessment with traditional in-person examination is limited. This study evaluated the concurrent validity and interrater reliability of video-based physiotherapy assessment versus face-to-face assessment in patients with knee pain. Methods: Patients with knee pain underwent randomized consecutive in-person and video-based assessments by experienced musculoskeletal physiotherapists. Clinical diagnoses were categorized into seven groups (red flag, yellow flag, arthrogenic, tendinopathy, patellofemoral pain, muscle sprain, neurogenic). Primary outcomes were intermethod agreement and Cohen’s kappa; sensitivity, specificity, PPV, NPV, and interrater reliability for video assessments were also reported. Results: Forty-five participants (mean age 38 ± 6.5 years; 55.6% female) completed the study. In-person and video-based assessments produced identical diagnoses in 43/45 cases (Cohen’s κ = 0.92, p < 0.001). Telehealth accuracy was high across all diagnostic categories (90–100%). Interrater agreement between video-based assessors was 93.3% (κ = 0.89, p < 0.001). Agreement between assessments was moderately associated with KOOS (r = 0.312, p = 0.037). Conclusions: In this selected pragmatic sample, video-based physiotherapy assessment demonstrated high concurrent agreement and excellent interrater reliability with face-to-face assessment. Given the study’s sample size, repeated-measures design, and lack of an independent reference standard, these results indicate feasibility and intermethod agreement rather than diagnostic equivalence. Video assessment may be a feasible option for triage and management in selected settings, but further research in larger, more diverse populations and evaluation against independent reference standards is required. Full article

Business-to-consumer (B2C) e-commerce firms operate in fast-changing digital markets, where timely interpretation of external signals may strengthen organisational agility. This study examines how four dimensions of competitive intelligence—market, technological, social, and competitor intelligence—relate to organisational agility in Croatian B2C e-commerce firms. The study adopted a pragmatic explanatory sequential mixed-methods design. Quantitative data were collected through an online survey, and 208 valid responses were analysed using reliability testing, construct-validity assessment, correlation analysis, and multiple regression. Qualitative follow-up evidence was used to support the interpretation of the quantitative results. The findings show that the effects of competitive intelligence dimensions on organisational agility are not uniform. In the final validated model, social intelligence emerged as the only significant positive predictor of organisational agility, while market intelligence, technological intelligence, and competitor intelligence did not show statistically significant effects. The study therefore suggests that, in this context, systematic attention to customer conversations, online feedback, and socially visible market signals may play a more decisive role in supporting agile organisational responses than other intelligence domains. The study contributes to the competitive intelligence and agility literature by showing that intelligence dimensions should be examined separately rather than treated as a single undifferentiated capability in digital commerce settings. Full article

Impacted mandibular third-molar surgery commonly causes early postoperative pain, swelling, and trismus. This randomized, controlled, three-arm parallel trial evaluated whether intra-alveolar corticosteroid delivery via an absorbable gelatin sponge improves postoperative recovery compared with a saline control. Fifty-five patients were assessed for eligibility; 37 healthy adults (18–35 years) undergoing standardized mandibular third-molar extraction were randomized to dexamethasone 8 mg (Decort^®), methylprednisolone 40 mg (Prednol^®), or control (saline), all applied intra-alveolarly using a gelatin sponge carrier. Doses were selected using standard systemic glucocorticoid equivalence tables as a pragmatic potency reference, acknowledging unknown intra-alveolar pharmacokinetics/bioavailability. The prespecified primary endpoint (used for sample size planning) was postoperative Day 1 VAS pain; key secondary endpoints were Day 1 analgesic consumption and Day 3 facial swelling. Pain (VAS), analgesic use, trismus, and facial swelling (tragus–pogonion, tragus–labial commissure, and angulus–canthus distances) were assessed on postoperative Days 1, 2, 3, and 7 by a blinded evaluator. Two participants in the methylprednisolone group did not attend postoperative visits. To address potential attrition bias, an Intention-to-Treat (ITT) sensitivity analysis using conservative control-median imputation was performed alongside the available-case analyses. A global False Discovery Rate (FDR) correction was also applied to control for multiplicity. In both analyses, the steroid groups showed lower Day 1 pain scores than the control group. Methylprednisolone was associated with lower Day 3 swelling values than control for the tragus–pogonion and angulus–canthus measurements. These findings should be interpreted as preliminary, given the small sample size, linear swelling measurements, and lack of blinding verification. Full article

Background: Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition for which non-pharmacological interventions remain the primary therapeutic approach. Although research output in this field has increased substantially, a comprehensive synthesis of its developmental trajectory and emerging directions is still lacking. Methods: We conducted a bibliometric analysis of publications on non-pharmacological interventions for ASD indexed in the Web of Science Core Collection between 2001 and 2025. Knowledge structures, research hotspots, and temporal trends were visualized and analyzed using CiteSpace. Results: The field has transitioned from an early focus on behavioral interventions in children to a diversified and interdisciplinary research ecosystem spanning the lifespan. Recent growth has been driven by the integration of neuroscience-based approaches, particularly neuromodulation techniques, alongside continued refinement of behavioral, sensorimotor, and complementary therapies. Increasing attention has been paid to individual heterogeneity, methodological rigor, and mechanism-oriented research. Current frontiers emphasize multimodal intervention strategies, neural plasticity-based mechanisms, and the development of personalized precision intervention frameworks. Conclusions: This bibliometric analysis delineates the intellectual evolution of non-pharmacological intervention research for ASD and identifies key research gaps, particularly the need for longitudinal and pragmatic studies targeting individualized treatment response. The findings provide an evidence-informed overview of current concepts and emerging research directions in non-pharmacological care for ASD, with important implications for future clinical research, intervention design, and strategic research planning. Full article