Search Results (20,910)

Metformin, widely prescribed for type 2 diabetes mellitus (T2D), has emerged as a systemic immunomodulator with effects that extend far beyond glycemic control. Recent advances in immunometabolism reveal that metformin modulates innate immune responses through coordinated cellular metabolic reprogramming and epigenetic modification, which collectively modulate the functional phenotype of innate immune cells. This narrative review summarizes current evidence regarding the immunomodulatory effects of metformin on the innate immune system, with a focus on immunometabolism and epigenetic regulation. It explores how metformin modulates innate immunity by altering cellular energy sensing, mitochondrial function, and nutrient utilization. Such metabolic changes and alterations further reshape chromatin structure and architecture, as well as transcriptional profiles and programs. Through the regulation of glycolysis, fatty acid oxidation, and histone modification landscapes, metformin regulates the phenotypes of innate immune cells, which can be pro-inflammatory, tolerogenic, or homeostatic. This conceptual framework presents a new understanding of metformin. As well as acting as an anti-inflammatory agent, it may regulate immune memory. Full article

This review aims to evaluate the potential of endometriosis models, especially patient-derived iPSC models, to gain deeper insights into the disease, thereby advancing our understanding and treatment of endometriosis. This comprehensive narrative review utilized a structured search of the PubMed, Scopus, and Web of Science databases, primarily covering literature published between January 2000 and May 2025. An expansive search strategy was employed to capture the full breadth of the field using keywords such as “endometriosis,” “induced pluripotent stem cells (iPSCs),” “patient-derived organoids,” “disease modeling,” and “epigenetics” without restrictive filtering, ensuring the integration of both foundational theories and emerging biotechnological advances. In total, over 170 peer-reviewed publications were analyzed, ranging from landmark genomic meta-analyses that have identified significant risk loci to state-of-the-art 3D-culture systems for modeling patient-specific endometrial disease. By synthesizing these diverse sources, the review bridges the gap between traditional anatomical classifications and modern molecular modeling to evaluate the potential of iPSC platforms for personalized medicine and therapeutic discovery. Endometriosis is a multifactorial gynecological condition that affects 176 million women worldwide and can significantly impair quality of life. It occurs when endometrium-like tissue grows outside the uterus, responsive to ovarian hormones, causing inflammation, pain, and discomfort, and leading to fibrotic tissue. World Health Organization estimates indicate that 6–10% of women suffer from this disorder, which can cause infertility and increase the risk of developing various types of cancer and autoimmune disorders. The use of patient-derived iPSC models serves to gain deeper insights into the disease by mimicking the endometrial tissue or lesions observed in affected individuals, thereby advancing our understanding and treatment of endometriosis. Full article

Morocco has developed one of the most comprehensive sustainability governance architectures among middle-income emerging economies, yet the relationship between its formal regulatory ambition and on-the-ground implementation effectiveness remains poorly understood. This narrative literature review provides an integrated, critically analytical account of Morocco’s sustainability governance system, organised around three interlocking dimensions: (i) a progressively strengthened legislative corpus anchored by the 2011 Constitution and Framework Law 99-12; (ii) a portfolio of national sustainability strategies aligning domestic policy with Paris Agreement commitments, Nationally Determined Contributions (NDCs), and the United Nations Sustainable Development Goals (SDGs); and (iii) corporate sustainability practices driven by regulatory obligations, international supply chain pressures, and ESG disclosure norms. Drawing on 124 sources, comprising 62 peer-reviewed articles, 38 legislative texts, and 24 institutional reports, and applying institutional isomorphism theory as an integrating analytical lens, the review advances three theoretical propositions concerning the conditions under which formal governance architectures translate into effective sustainability outcomes. It further proposes a validated conceptual framework and develops a comparative positioning of Morocco against peer economies (Tunisia, Egypt, South Africa, and Turkey). Critical implementation gaps are identified in enforcement capacity, SME integration, sustainability data infrastructure, and green finance, contributing a balanced and evidence-grounded assessment of Morocco’s sustainability transition. These findings offer actionable insights for policymakers, regulators, and business leaders operating in the Moroccan and broader African context. Full article

Mucopolysaccharidosis (MPS) are a group of inherited lysosomal storage genetic disorders that affect the body’s ability to break down glycosaminoglycans (GAGs) due to the deficiency of required enzymes. This leads to depositions of these GAGs in various tissues and organs resulting in multi-systemic manifestations including pulmonary and sleep related issues. In recent years, there have been significant advancements in therapeutic options and supportive management which have led to the overall improvement in respiratory care, culminating in improved quality of life for MPS patients. Management of pulmonary and sleep disorders in mucopolysaccharidosis requires a multidisciplinary approach due to the multi-systemic affectation of the genetic disorders. Therapeutic options such as enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) have yielded varying success in mitigating respiratory complications. Emerging treatments such as gene therapies have shown exciting and promising results thus far. Supportive therapies such as airway clearance, regular vaccination and use of positive airway pressure devices are also essential. Pre-operative airway and anesthesia planning is critical to mitigate peri-operative and post-operative complications. Early diagnosis, close monitoring and a patient focused individualized approach are essential for respiratory optimization and overall improvement in clinical outcomes. This review article aims to discuss these advancements in a comprehensive format, making it accessible to medical providers who care for this subset of patients. Full article

Background: Hemophilia care has undergone a major therapeutic transformation with the introduction of extended half-life products, non-replacement therapies, and gene therapy. However, the benefits of these advances are not equally distributed worldwide, and their impact on long-term musculoskeletal outcomes remains uncertain. Objective: To analyze global disparities in hemophilia care and research production in the context of recent therapeutic advances, with particular attention to musculoskeletal management, physiotherapy, and scalable strategies for resource-limited settings. Methods: A narrative review with a structured literature search was conducted. Two conceptual blocks were explored: global disparities and access to care in hemophilia, and recent therapeutic advances, including non-replacement therapies, extended half-life products, and gene therapy. Retrieved records were screened using Rayyan, and a structured workflow diagram was used to summarize the literature identification and selection process. A descriptive analysis was also performed to identify representative authors, institutions, and geographic patterns in hemophilia research. Results: The evidence shows substantial global disparities in diagnosis, access to treatment, healthcare infrastructure, and research production. Scientific output remains concentrated in high-income countries, while low- and middle-income regions are underrepresented. Advanced therapies consistently reduce bleeding rates and treatment burden, but concerns remain regarding access, affordability, durability, breakthrough bleeding, and long-term structural joint outcomes. Musculoskeletal complications, including subclinical bleeding and hemophilic arthropathy, remain clinically relevant despite improved hematologic control. Conclusions: The current paradigm shift in hemophilia care is not uniformly experienced worldwide. Addressing global disparities requires not only expanding access to advanced therapies, but also strengthening research capacity, implementing multidisciplinary care models, and integrating scalable interventions such as physiotherapy, patient education, and simplified diagnostic tools. Accessible musculoskeletal assessment strategies may help improve early detection, functional outcomes, and equity of care in resource-limited settings. Full article

Human papillomavirus (HPV) infection is a major driver of anogenital disease and virus-related carcinogenesis. Although most infections resolve spontaneously, persistent infection with high-risk genotypes may progress to high-grade squamous intraepithelial lesions (HSILs) and cancer, particularly in the setting of impaired immune surveillance. Unlike previous HPV-related reviews focused primarily on cervical disease, vaccination, or isolated immunosuppressed populations, this narrative review comparatively examines the clinical expression, colposcopic findings, screening strategies, and therapeutic implications of HPV-related disease across the immunological spectrum. This narrative review provides an integrative synthesis of HPV-related disease in the female lower genital tract across the immunological spectrum. A structured, non-systematic search of PubMed/MEDLINE, Scopus, and Web of Science was conducted using terms related to “human papillomavirus”, “HPV”, “cervical intraepithelial neoplasia”, “colposcopy”, “immunosuppression”, “HIV”, and “vaccination”. Immunosuppressed populations, including individuals living with HIV, transplant recipients, and patients receiving immunosuppressive therapy, exhibit higher rates of persistent infection, multifocal disease, recurrence, and progression to HSIL and invasive malignancy. These patients also present greater diagnostic complexity, broader anatomical involvement, and reduced response to conventional treatment. Rather than representing a uniform condition, HPV-related disease reflects a biologically dynamic spectrum shaped by host immune competence. This review highlights the distinct clinical, colposcopic, and therapeutic challenges observed in immunosuppressed populations and reinforces the need for individualized, risk-adapted strategies integrating contemporary advances in screening, vaccination, and HPV-related disease management. Full article

Previous research has shown that both victim intoxication and narrative framing can influence the levels of victim blame. However, far less attention has been paid to how coercive strategy and narrative framing may interact to shape victim-blaming judgements and perceptions of sexual assault. The present study addresses this gap by examining how combinations of coercive strategies (physical force versus alcohol facilitated), narrative framing (active versus passive), and rape myth acceptance (RMA) influence victim blame and the recognition of sexual assault. Participant gender and age were also assessed in relation to RMA and victim-blaming attitudes. A total of 202 participants aged 18–63 (78.7% of women, 21.3% of men, M_Age = 28.93, SD = 14.36) completed an online survey evaluating vignettes depicting a male perpetrator sexually assaulting a female victim. Age significantly predicted victim blaming, with older participants assigning greater blame to the victim. Gender predicted both RMA and victim blame, with men reporting higher RMA and greater victim blame than women. Active framing in both the physical force and alcohol-use conditions reduced participants’ recognition of the incident as sexual assault. Participants with lower RMA consistently reported lower victim blame across conditions, and were more likely to identify the incident as sexual assault in the physical force condition. These findings highlight the influence of coercive strategies and the importance of victim-centred language in policing, legal, and media contexts, where narrative framing can meaningfully shape the recognition of sexual assault. Full article

Radiotherapy is central to the treatment of nasopharyngeal carcinoma and selected sinonasal malignancies, but sinonasal toxicity remains incompletely characterized. Radiation-induced rhinosinusitis (RIR) is increasingly recognized after head-and-neck radiotherapy, particularly in nasopharyngeal carcinoma, where the paranasal sinuses and drainage pathways may receive substantial incidental dose. Reported prevalence varies widely because studies use different endpoints, including radiologic mucosal thickening, endoscopic inflammation, and patient-reported symptoms. Across available nasopharyngeal carcinoma cohorts, imaging-defined sinonasal inflammatory changes are common, with reported rates generally ranging from approximately 30% to more than 70% depending on timing, radiation technique, and diagnostic criteria. This narrative review summarizes current evidence on the epidemiology, pathophysiology, dosimetric predictors, imaging findings, prevention, and management of RIR. Radiation-induced sinonasal injury appears to arise from epithelial damage, impaired mucociliary clearance, altered local defense, and chronic mucosal remodeling. Available data suggest that higher doses to the paranasal sinuses and drainage pathways, baseline sinus disease, and tumor extension into sinonasal structures increase risk, although validated dose constraints are not yet established. We propose a harmonized reporting framework that integrates symptoms, endoscopy, imaging, dosimetry, baseline sinonasal status, and oncologic context. Greater recognition of RIR as a clinically meaningful survivorship toxicity may support more consistent outcome reporting, prospective studies, and future radiation-planning strategies aimed at reducing sinonasal morbidity. Full article

Edible insects are increasingly recognized as a viable alternative protein source, offering a potentially sustainable approach to addressing global food security challenges. This narrative review critically examines the nutritional composition, environmental advantages, techno-functional attributes, and potential applications of insect-based proteins within human food systems. Edible insects are characterized by high protein content, favourable essential amino acid profiles, and appreciable levels of key micronutrients, rendering them nutritionally comparable to conventional livestock-derived proteins. Moreover, insect production systems generally require substantially lower inputs of land, water, and feed, resulting in comparatively lower greenhouse gas emissions and reduced overall environmental burden. Despite these advantages, broader adoption remains constrained by challenges related to regulatory heterogeneity, food safety concerns, and limited consumer acceptance. Overall, the available evidence suggests that edible insects can function as a nutritionally adequate and environmentally sustainable complementary protein source; however, significant variability in nutrient composition, limitations in standardized safety assessment, and socio-cultural barriers currently restrict their large-scale integration into mainstream food systems. In addition, inconsistencies in analytical methodologies and reliance on in vitro data further complicate cross-study comparisons and translational relevance. Future research should focus on standardization of rearing and processing conditions, harmonization of evaluation frameworks (e.g., protein quality indices), comprehensive safety assessments, and well-designed clinical studies to validate nutritional and functional benefits, alongside the development of effective strategies to improve consumer acceptance and support regulatory alignment across regions. Full article

Chronic overlapping pain conditions (COPCs) refer to a set of chronic pain disorders that frequently co-occur and may involve partially overlapping mechanisms. The U.S. National Institutes of Health currently recognizes ten COPCs: fibromyalgia, painful temporomandibular disorders, chronic low back pain, chronic migraine headache, chronic tension-type headache, irritable bowel syndrome, endometriosis, interstitial cystitis/bladder pain syndrome, vulvodynia, and myalgic encephalomyelitis/chronic fatigue syndrome. When multiple COPCs coexist, they are associated with a disproportionate multimorbidity burden, including greater pain, poorer psychological well-being, functional limitations, disability, fatigue, sleep disturbances, diminished quality of life, and increased healthcare utilization. Despite their impact, COPCs remain under-recognized, underdiagnosed, and undertreated. Combining structured literature searches and citation tracking with narrative syntheses, this review examines comorbid relationships, the burden of multimorbidity, and potentially overlapping nociplastic mechanisms. By adopting a multimorbidity-based perspective rather than a one-disease, one-treatment approach, it highlights barriers to care—including limited clinical awareness, under-recognition of additional COPCs, limited mechanistic understanding, and fragmented care—and proposes integrated strategies emphasizing prevention, systematic screening, mechanism-informed assessment, and coordinated, patient-centered multimodal management. Full article

Implant screw loosening remains among the most frequently reported technical complications in implant-supported prostheses and may compromise prosthetic stability, maintenance requirements, and long-term clinical outcomes. Etiology is multifactorial and involves biomechanical, prosthetic, occlusal, and patient-related factors. This narrative review aimed to synthesize medium- and long-term clinical evidence (>5 years whenever available) regarding mechanisms, prevalence, and risk factors associated with screw loosening in implant-supported restorations. A structured literature search was conducted in PubMed, Web of Science, Cochrane Library, and EBSCOhost to identify clinical studies, randomized controlled trials, systematic reviews, and meta-analyses. Evidence regarding preload, implant–abutment connection design, retention type, implant splinting, framework fit, abutment angulation, implant dimensions, occlusal loading, parafunction, full-arch restorations, and torque protocols was critically interpreted. Current evidence indicates that screw loosening is influenced by inadequate preload, unfavorable occlusal forces, cantilevers, angulated abutments, framework misfit, and parafunctional habits. Single-unit and screw-retained restorations appear to exhibit higher complication rates in several studies, although findings remain inconsistent. Internal connections and splinting may improve mechanical stability; however, superiority has not been conclusively demonstrated. Most screw loosening events occur during the early functional period, emphasizing the importance of preload optimization, occlusal control, maintenance, and follow-up. High-quality long-term comparative studies remain limited. Full article

Horizontal nystagmus is still commonly interpreted at the bedside through a pragmatic peripheral-versus-central dichotomy. Although this heuristic is often clinically useful, it may be misleading because distributed brainstem–cerebellar disorders can generate peripheral-appearing phenotypes. This paper presents a narrative clinical–conceptual review proposing that a substantial subset of horizontal nystagmus patterns may be understood more coherently as expressions of dysfunction within a coupled vestibulo-ocular integrative network rather than as direct signatures of a single lesion site. Within this framework, two core dynamical domains are separated conceptually: a vestibular nuclei (VN)-centered velocity-storage process and an NPH-centered gaze-holding integrator. These processes are proposed to operate under cerebellar regulatory influence, with the nodulus–uvula (NU) acting as a plausible regulator of storage gain, temporal persistence, adaptation stability, and oscillatory behavior. Clinically, the velocity-storage domain is expressed through low-frequency vestibulo-ocular reflex behavior and optokinetic after-nystagmus-related dynamics, whereas the gaze-holding domain is expressed through eccentric gaze stability, gaze-evoked nystagmus, and post-saccadic drift. This framework carries a clinically relevant implication: horizontal nystagmus phenotypes may be interpreted more effectively by asking which functional process is predominantly abnormal—gaze holding, storage-related vestibular persistence, or cerebellar regulatory stability—rather than by relying solely on a binary peripheral–central label. On this basis, we outline a clinician-facing workflow linking gaze dependence, periodicity, direction reversals, head-shaking behavior, and Alexander-law mismatch to operational bedside criteria and candidate quantitative readouts. The proposed model is intended as a clinical–conceptual framework rather than a deterministic localization tool. Its main value lies in organizing discordant vestibular findings, strengthening the mechanistic interpretation of bedside and instrumented observations, and identifying testable directions for future validation studies in acute dizziness and ocular motor disorders. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis, biological heterogeneity, and persistent challenges in staging and treatment selection. This narrative review summarizes current and emerging applications of AI across lung cancer screening and early detection, imaging-based staging and prognostication, tissue and liquid biopsy-based tumor characterization, treatment planning, surgical and intraoperative guidance, and drug discovery. In imaging, deep learning models have demonstrated high performance in pulmonary nodule detection, risk stratification, and prediction of molecular alterations, while also showing promise in improving screening efficiency and reducing interpretive variability. In pathology and liquid biopsy domains, AI enables prediction of driver mutations, immunotherapy response, and survival outcomes directly from histopathology slides, circulating tumor DNA, and other blood-based biomarkers, facilitating minimally invasive precision oncology approaches. In treatment planning and delivery, AI systems are being developed to support clinical decision-making, surgical planning (through advanced image segmentation and delineation of operative anatomy), and intraoperative navigation through robotic and computer vision-enabled platforms. Despite these advances, significant barriers remain, including limited real-world validation, algorithmic biases, workflow integration issues, and unresolved ethical and legal concerns. Future progress will depend on the development of transparent, clinically validated, and generalizable AI systems that augment rather than replace the expertise of clinical providers and healthcare teams. Active engagement from pulmonologists, oncologists, radiologists, and thoracic surgeons will be essential in guiding safe implementation and ensuring that AI-driven innovations translate into meaningful improvements in patient outcomes. Full article

In Indian religious traditions, pātāla denotes a seven-layered subterranean realm beneath the earth, a composite space that combines cosmological stability with mythic expressiveness. It serves as the dwelling of nāgas and asuras and connects with the human world through rivers and caves. Although Buddhist literature retains narratives about these beings and their splendid abodes, it never accepted pātāla as an independent cosmological unit. This article examines Pāli, Chinese, Tibetan, and Sanskrit Buddhist sources in comparison with Hindu epic and Purāṇic literature and analyzes the translation of pātāla in Chinese versions. It argues that Buddhism engaged in selective restructuring by de-emphasizing pātāla’s cosmological hierarchy and subordinating it to the Mount Sumeru framework, while transforming it in esoteric ritual literature into a liminal field of practice accessible through mantra, mudrā, and specific practices. Utilizing Arnold van Gennep’s liminality theory, the study shows that these spaces serve as an intermediary ritual field in Buddhist practice. Through ritual separation, liminal experience, and reintegration, practitioners acquire extended lifespan and merit that support the Mahāyāna goal of perfecting the two accumulations and attaining Buddhahood. The findings suggest that religious concepts cross traditions through disassembly, detachment, and functional reconfiguration rather than wholesale transplantation. Full article

Atopic dermatitis (AD) is increasingly interpreted through frameworks emphasizing barrier dysfunction, type 2 cytokine signaling, pruritus pathways, and microbial dysbiosis, often relegating IgE-mediated mechanisms to secondary roles. In this narrative review, we synthesize historical, clinical, immunologic, and histopathologic evidence to propose a conceptual model in which IgE-bearing antigen-presenting cells (APCs)—including Langerhans cells, inflammatory dermal dendritic cells, and inflammatory dendritic epidermal cells (IDECs)—participate in an IgE-dependent amplification loop that may contribute to the chronicity of extrinsic (IgE-associated) AD. Evidence from human studies indicates that FcεRI-expressing APCs can acquire environmental allergens through IgE, enhancing antigen uptake and T-cell activation, while mast cells and basophils further reinforce type 2 inflammation through IgE-dependent and IgE-augmented pathways. Although these mechanisms have been described across distinct experimental and clinical contexts, their integration into a unified pathogenic circuit remains hypothesis-driven. We therefore present an interpretive framework that organizes these partially validated mechanisms into a coherent model linking cutaneous sensitization, allergen capture, APC activation, Th2 polarization, and spongiosis formation. This conceptual synthesis aims to reposition IgE-mediated processes within the broader pathophysiology of extrinsic AD and to highlight potential therapeutic implications for targeting IgE–FcεRI signaling and IgE-dependent APC biology. Full article