Search Results (55)

Olfactory (or odorant) receptors (ORs) were initially characterized in 1991 by Drs. Richard Axel and Linda Buck, and subsequent additional efforts have contributed to our understanding of their canonical function in odorant identification in the nasal cavity, including ligands for many of the ORs and the signaling pathways involved. More recently, OR transcripts and proteins have been identified in cells and organs outside of the nasal cavity, ranging from skin to sperm to tumors, suggesting that they have biological roles in ectopic locations other than their canonical function of odorant molecule detection in the nose. This mini narrative review discusses ectopic human ORs and their potential ligand-activated functions in the skin, lung, and sperm, as well as in diseases such as nonalcoholic steatohepatitis (NASH), melanoma and prostate cancer. Full article

In recent years, there has been an unprecedented upsurge in opioid prescriptions for pain management. Consequently, the widespread availability of these medicines has led to an increase in misuse and abuse. This has led to a greater number of overdose-related deaths. The high prevalence of drug misuse was born of multiple and complex societal factors. However, from a medical perspective, critical contributors to the dire consequences of the crisis have been the need for chronic pain relief, as well as mental health issues within communities. Chronic pain coupled with psychological distress exacerbates patients’ predicaments and thus further fuels the crisis. Anxiety and depression have bidirectional and complex relationships with pain. The somatic symptoms associated with anxiety potentially worsen pain, whilst pain emanating from a chronic condition worsens anxiety. The same relational dynamic applies to depression and pain. Thus, these psychopathological states may be major contributors to the opioid abuse epidemic. Thus, psychosocial management as a first-line treatment instead of starting with drug treatments seems an enlightened approach to this problem. Cognitive behavioral therapy (CBT) has been proven to be effective in managing specific symptoms associated with chronic pain. Similarly, patient education has been shown to be a viable alternative to drugs for certain aspects of chronic pain treatment. We consider that the opioid crisis could be addressed with a greater reliance and emphasis on non-pharmacological approaches to managing chronic pain patients. This mini-review examines non-pharmaceutical and monitoring-based interventions to reduce opioid misuse risk among adults prescribed opioids for chronic non-cancer pain. Studies were identified through PubMed/MEDLINE, Scopus, and Google Scholar using terms related to chronic pain, prescription opioid misuse, opioid use disorder, cognitive behavioral therapy, patient education, prescription drug monitoring programs, digital health, telehealth, and non-pharmacological interventions. Studies were included if they focused on adults with chronic pain who were prescribed opioids or at risk of misuse, and evaluated interventions aimed at reducing unsafe opioid use, misuse risk, or opioid-related harm. Evidence was synthesized narratively to identify key intervention approaches, limitations, and clinical implications. Full article

Background/Objectives: Vestibular evoked myogenic potentials (VEMPs) and the video head impulse test (vHIT) enable receptor-specific assessment of otolithic organs and semicircular canals. Their increasing use has revealed selective or apparently isolated vestibular abnormalities, although the clinical significance of these findings remains uncertain. This mini-review examines selective otolithic and semicircular canal dysfunction, with emphasis on diagnostic interpretation, methodological limitations, and future research needs. Methods: A structured narrative review of PubMed/MEDLINE and Scopus was conducted, focusing on studies reporting isolated, selective, or disproportionate vestibular abnormalities assessed by VEMPs and/or vHIT. Relevant original studies, case series, case reports, reviews, and diagnostic or consensus papers were considered. Results: Selective otolithic dysfunction may involve the utricle, saccule, or both and is often associated with imbalance, tilting, swaying, spatial disorientation, nausea, or postural instability. Selective semicircular canal dysfunction may involve one or more canals and may present with vertigo, dizziness, nystagmus, or gait instability. Similar VEMP and vHIT patterns occur across vestibular neuritis, Ménière’s disease, vestibular migraine, benign paroxysmal positional vertigo, bilateral vestibulopathy, superior semicircular canal dehiscence, vestibular schwannoma, central vestibular disorders, systemic diseases, and idiopathic presentations. Conclusions: Selective vestibular abnormalities should be interpreted as context-dependent laboratory findings rather than discrete disease entities. Their value depends on reproducibility, anatomical plausibility, clinical concordance, complementary testing, and longitudinal follow-up. Full article

Narrative extraction builds coherent ordered sequences of documents that trace how concepts develop over time, and is a growing area of information retrieval. In this work we focus on scientific literature, using a corpus of 3549 IEEE visualization research papers (1990–2022). A natural hypothesis is that augmenting embedding-based pathfinding with explicit domain knowledge should improve narrative quality. We present the Knowledge-Coherence Framework (KCF), which integrates structured metadata from OpenAlex into narrative extraction (building on the Narrative Trails algorithm), and conduct a systematic empirical investigation along three axes: (1) the effect of embedding model choice (MiniLM vs. SPECTER), (2) the effect of knowledge augmentation (with and without, plus sensitivity to the knowledge weight $\alpha$), and (3) the reliability of LLM-based evaluation (cross-agreement among 13 large language models). Throughout, mathematical coherence denotes the geometric mean of angular and topic similarity between consecutive documents along a path—an automatic, model-computed quantity inherited from Narrative Maps and Narrative Trails—while narrative quality refers to the LLM-judged construct. Using up to 600 evaluation pairs, we find that embedding model choice has a large effect on mathematical coherence (SPECTER: 0.94 vs. MiniLM: 0.81) and that, contrary to expectations, knowledge augmentation does not improve LLM-judged narrative quality—it slightly decreases it for both embeddings. Notably, the two notions dissociate: SPECTER produces the most mathematically coherent paths, yet MiniLM paths receive the highest LLM narrative-quality scores (5.87 vs. 5.36 out of 10). Alpha sensitivity analysis over five values ($\alpha \in \{0.0,0.3,0.5,0.7,1.0\}$, 500 pairs) confirms that LLM scores remain essentially flat while mathematical coherence steadily declines with increasing knowledge weight. Cross-model evaluation with 13 LLM judges shows high inter-model agreement (median Pearson $r=0.71$), supporting evaluation reliability. The main practical takeaways are that (i) embedding model choice, not knowledge augmentation, is the more consequential design decision, and (ii) mathematical coherence and LLM-judged narrative quality are distinct optimization targets that practitioners should not conflate. Full article

Non-alcoholic fatty liver disease affects approximately thirty percent of the global population, yet public awareness remains dangerously low among young adults facing occupational risk factors. This study introduces the Fatty Liver Awareness Game (FLAG), an educational serious game designed to improve liver health literacy among software engineering students at the University of Guayaquil. While evaluated with this specific sample, FLAG is intended for the broader target population of young adults in developing nations who face occupational sedentary risk and limited access to preventive health education. Through a controlled experiment with fifty participants randomly assigned to game-based or traditional lecture instruction, the game demonstrated superior effectiveness, with a twenty-percentage-point advantage in post-test scores and a seventy-two percent reduction in incorrect responses compared to fifty percent in the lecture group. The large effect size (Cohen’s d = 1.43) and reduced performance variability among game participants indicate that interactive, feedback-rich learning environments can outperform passive instruction for this population and content domain. While the present design does not isolate the contribution of individual game elements—such as narrative framing, explanatory feedback, or mini-game interleaving—the results establish FLAG as a replicable model for digital health interventions targeting underserved populations at critical developmental junctures. Future component analyses are needed to determine which specific design features drive the observed advantages. Full article

Childhood absence epilepsy (CAE) is one of the most common epilepsy syndromes in childhood and has traditionally been regarded as a condition with a favorable neurological prognosis. However, increasing evidence suggests that CAE is associated with functional disturbances in neuronal networks that extend beyond seizure generation and may involve sleep and wakefulness regulation. Methods: This narrative mini-review summarizes and critically discusses current clinical and neurophysiological evidence regarding alterations in sleep architecture and sleep electroencephalographic (EEG) microstructures in children with CAE, based on a focused analysis of selected clinical and observational studies. Results: The available data suggest that children with CAE, particularly before treatment initiation, may exhibit sleep macrostructure abnormalities, including reduced total sleep time, prolonged rapid eye movement sleep latency, increased arousal frequency, and decreased sleep efficiency. In addition, changes in sleep microstructure have been reported, most notably reduced sleep spindle density during stage-N2 sleep, especially in patients with concomitant cognitive impairment. These findings may reflect alterations in thalamocortical network function, although current evidence remains limited and heterogeneous. Conclusions: Sleep disturbances appear to represent an important component of the clinical phenotype of childhood absence epilepsy. Assessing the sleep architecture and sleep EEG microstructure, particularly sleep spindles, may provide insights into network dysfunction and cognitive vulnerability; however, further studies are needed to clarify their clinical utility. Full article

Background/Objectives: Time-constrained consultations in high-volume settings can crowd out patient-centered communication, while AI-generated advice may face algorithm aversion when it lacks a humanistic dimension. This study examined whether a brief narrative-based prompt could improve coded patient-facing communication features in an LLM relative to both clinicians and an unprompted model on authentic patient queries. Methods: We conducted a three-condition comparative evaluation using a stratified sample of 1000 de-identified MedDialog-CN consultations (2016–2020). For each consultation, the same patient query was used to generate (i) a zero-shot GPT-o3-mini response and (ii) a narrative-prompted GPT-o3-mini response; the original physician reply served as the human baseline. Responses were annotated with a pre-specified schema operationalizing four communication dimensions—Storytelling, Empathy, Personalization, and Clarity—with expert adjudication. Frequency-based indicators were summarized as mean events per consultation, and binary indicators as proportions; secondary checks captured unwarranted certainty and risk-relevant language. Results: Narrative prompting shifted coded patient-facing communication from sparse and selectively deployed (clinicians and zero-shot AI) to more routine and standardized. Across the reported communication measures, the prompted model showed the most favorable overall pattern, with higher narrative-device use, empathic support, contextual tailoring, and terminology explanation, alongside more frequent consideration of patient preferences and markedly higher rates of emotion–symptom linkage and the presence of a patient-centered narrative framework. Conclusions: Narrative prompting may offer a lightweight and potentially scalable strategy for improving patient-facing communication in Chinese asynchronous, text-based online consultations. An important next step is calibration: humanistic cues should be delivered selectively and safely so that responses remain credible, locally feasible, and cognitively manageable. Full article

Background/Objectives: The potential role of domestic animals in DNA transfer, persistence, prevalence and recovery (TPPR) warrants careful consideration in forensic contexts. This mini narrative review aims to provide an updated overview of human DNA transfer involving household dogs and cats as vectors, to clarify their forensic relevance, and to identify key considerations for the design of future experimental research. Methods: A narrative review was conducted using multiple electronic databases as search engines without restriction related to the timing of publication. Results: Experimental evidence shows that dogs and cats readily acquire human DNA following even brief contact, acting as reservoirs for primary DNA transfer. Once acquired, human DNA can be redistributed via secondary transfer to a wide range of substrates, such as gloved hands, vehicle interiors, clothing, and surfaces. Moreover, multi-step and higher-order transfer events have been documented, highlighting the complexity of DNA transfer involving household animals. Conclusions: The sampling on pets may be included in certain scenarios and may contribute to building a Bayesian network together with the experimental data. To deal with uncertainty during probability assignment, more experimental data, especially addressing the main variables impacting DNA TPPR involving pets, should be generated and are highly needed to assist in activity level evaluation. Full article

Background and Objectives: Because of its consistently high stone-free rates (SFRs), percutaneous nephrolithotomy (PCNL) continues to be the first-line treatment for renal stones larger than 20 mm. Standard 24 to 30 Fr access tracts, however, are linked to access-related morbidity, such as bleeding, pain, and extended hospital stays. These restrictions have led to progressive tract miniaturization and the development of mini-PCNL, ultra-mini PCNL, and micro-PCN techniques. Materials and Methods: We performed a narrative review of studies published through January 2026 using PubMed and Google Scholar. Search terms included percutaneous nephrolithotomy, mini-PCNL, ultra-mini PCNL, micro-PCNL, and vacuum-assisted PCNL. Original studies, systematic reviews, and meta-analyses reporting clinical outcomes, complications, and advancements were selected, whereas conference abstracts, non-English papers, and articles without accessible full text were excluded. Results: Across randomized trials, miniaturized PCNL generally preserves efficacy when patients are selected appropriately. Across randomized trials and meta-analyses, miniaturized PCNL achieved stone-free rates comparable to standard PCNL (typically ~80–90% for stones ≤20 mm and similar rates in selected stones >2 cm), while demonstrating lower hemoglobin decrease (mean difference approximately −0.6 to −1.0 g/dL), reduced transfusion rates, and shorter hospital stays, at the cost of longer operative time (mean difference ~8–12 min). On the other hand, operative time may increase, and smaller working channels can make visualization and fragment evacuation more demanding as stone burden rises. Raised intrarenal pressure is a recurring safety issue because it may increase infectious risk unless drainage is actively managed. Recent innovations aim to address these limitations, including vacuum-assisted access sheaths, pressure-controlled irrigation, improved laser and lithotripsy platforms, image-fusion guidance, navigation systems, and robotic assistance. Conclusions: PCNL now spans a spectrum of tract sizes rather than a single standard approach. When chosen appropriately and performed with attention to pressure control and fragment evacuation, miniaturized PCNL can reduce morbidity without sacrificing stone clearance. Future advancements in percutaneous stone surgery are more likely to rely on integrated technological solutions that improve accuracy, safety, and repeatability than on additional tract size reduction. Full article

Automating ICD-10 coding from discharge summaries remains demanding because coders analyze clinical narratives while justifying decisions. This study compares three automation patterns: PLM-ICD as a standalone deep learning system emitting 15 codes per case, LLM-only generation with full autonomy, and a hybrid approach where PLM-ICD drafts candidates for an agentic LLM audit to accept or reject. All strategies were evaluated on 19,801 MIMIC-IV summaries using four LLMs spanning compact (Qwen2.5-3B-Instruct, Llama-3.2-3B-Instruct, Phi-4-mini-instruct) to large-scale (Sonnet-4.5). Precision guided evaluation because coders still supply any missing diagnoses. PLM-ICD alone reached 55.8% precision while always surfacing 15 suggestions. LLM-only generation lagged severely (1.5–34.6% precision) and produced inconsistent output sizes. The agentic audit delivered the best trade-off: compact LLMs reviewed the 15 candidates, discarded weak evidence, and returned 2–8 high-confidence codes. Llama-3.2-3B-Instruct, for example, improved from 1.5% as a generator to 55.1% as a verifier while trimming false positives by 73%. These results show that positioning LLMs as quality controllers, rather than primary generators, yields reliable support for clinical coding teams, while formal recall/F1 reporting remains future work for fully autonomous implementations. Full article

Background and Clinical Significance: Over the last two decades, glucagon-like peptide-1 (GLP-1) receptor agonists have dramatically improved the management of type 2 diabetes mellitus and obesity. Currently, little is known about the use of semaglutide (a second-generation GLP-1 receptor agonist) in patients with X chromosome abnormalities. Herein, we describe the therapeutic use of semaglutide in a woman with a partial deletion of the X chromosome long arm (partial Xq deletion) and comorbid obesity. We also conducted a narrative mini-review on overweight, obesity and common metabolic derangements in patients with partial Xq deletions and Turner syndrome. Case Presentation: A 65-year-old Italian woman with a partial Xq deletion, class 1 obesity, insulin resistance, prediabetes, hypercholesterolemia and metabolic dysfunction-associated steatotic liver disease (MASLD) was referred to our Institution for persistent difficulty in managing excess body weight despite regular adherence to different structured physical activity programs and hypocaloric diets. Therefore, we prescribed a combination therapy based on low-dose metformin (500 mg/day) and once-weekly subcutaneous semaglutide (as an adjunct to lifestyle intervention). At 5 months after initiation of the combination therapy, blood tests showed metabolic improvements, including improvement of prediabetes (0.3-percentage-point reduction in glycated hemoglobin [HbA1c] values) and normalization of markers of insulin sensitivity and insulin resistance (QUICKI, HOMA-IR and TyG index). At 8 months, the patient showed substantial weight loss, which amounted to 13.8 kg (percent total body weight loss: 20.95%), and was accompanied by a notable reduction in waist circumference (−14.1 cm). Moreover, body mass index (BMI)-based weight status improved from class 1 obesity to overweight: BMI value of 25.1 kg/m² at 8 months vs. 31.8 kg/m² at baseline (near-normalization of BMI values). Bioelectrical impedance analysis (BIA) revealed that the patient’s overall weight loss consisted of 74.6% fat mass (FM) loss (−10.3 kg) and 25.4% fat-free mass (FFM) loss (−3.5 kg). Despite the expected FFM reduction in absolute terms, percent FFM increased at 8 months (+9.6%). This increase in percent FFM was accompanied by a reduction in percent FM at 8 months (−9.6%), indicating an overall improvement in body composition. Normalization of percent FM and FFM values (28.6% and 71.4%, respectively) was also achieved at 8 months. These body composition changes are in line with those observed in clinical trials investigating the use of semaglutide in patients with overweight or obesity. At 6 months, an abdominal ultrasound also showed the disappearance of the sonographic characteristics suggestive of mild-to-moderate hepatic steatosis. Low-dose metformin (500 mg/day) and subcutaneous semaglutide (up to a weekly dose of 1.7 mg) were well tolerated by the patient. Conclusions: To the best of our knowledge, this is the first case documenting the effective use of once-weekly subcutaneous semaglutide plus low-dose metformin combination therapy for the treatment of obesity and prediabetes in a woman with a partial Xq deletion. Large prospective cohort studies are warranted to better investigate the safety and efficacy profile of semaglutide (alone or in combination with metformin) in patients with numerical and structural X chromosome abnormalities, comorbid overweight/obesity and related metabolic disorders. Full article

Autosomal short tandem repeat (STR) markers remain the cornerstone of modern forensic genetics, providing exceptional power for individualization, kinship verification, and reconstruction of complex investigative cases. Over the last decade, the field has undergone a major technological transition from length-based capillary electrophoresis (CE) toward sequence-level characterization using massively parallel sequencing (MPS), enabling detection of internal sequence variants (isoalleles) and flanking-region polymorphisms that substantially increase discriminatory power in many forensic contexts. Although MPS is increasingly adopted in forensic laboratories, implementation remains dependent on infrastructure, cost considerations, validation requirements, and jurisdiction-specific legal frameworks. This review synthesizes the molecular mechanisms underlying STR variability, including replication slippage and mutation processes, and critically evaluates the transition to sequencing-based analysis. Particular attention is given to analytical challenges such as stochastic effects in ultra-low-template DNA and PCR inhibition in degraded samples. Special emphasis is placed on identification of skeletal remains from mass graves and historical contexts, where hierarchical analytical strategies—from mini-STR approaches to MPS-based workflows—enable recovery of highly fragmented DNA. The review also examines the evolution of probabilistic genotyping (PG), highlighting the importance of algorithmic transparency and reproducible analytical frameworks for judicial applications. By integrating technological advances with practical forensic challenges, this review outlines a comprehensive framework for implementing high-resolution STR analysis in contemporary genomic casework. As a narrative synthesis, the conclusions reflect currently available published evidence and acknowledge variability in validation status, implementation practices, and regional forensic infrastructures. Full article

This study examined whether large language models (LLMs) can generate clinically realistic profiles of cognitive decline and whether simulated deficits reflect architectural constraints rather than superficial role-playing artifacts. Using GPT-4o-mini, we generated synthetic cohorts (n = 10 per group) representing healthy aging, mild cognitive impairment (MCI), and Alzheimer’s disease (AD), assessed through a conversational neuropsychological battery covering episodic memory, verbal fluency, narrative production, orientation, naming, and comprehension. Experiment 1 tested whether synthetic subjects exhibited graded cognitive profiles consistent with clinical progression (Control > MCI > AD). Experiment 2 systematically manipulated prompt context in AD subjects (short, rich biographical, and few-shot prompts) to dissociate robust from manipulable deficits. Significant cognitive gradients emerged (p < 0.001) across eight of thirteen domains. AD subjects showed impaired episodic memory (Cohen’s d = 4.71), increased memory intrusions, and reduced narrative length (d = 3.07). Critically, structurally constrained memory tasks (episodic recall, digit span) were invariant to prompting (p > 0.05), whereas generative tasks (narrative length, verbal fluency) showed high sensitivity (F > 100, p < 0.001). Rich biographical prompts paradoxically increased memory intrusions by 343%, indicating semantic interference rather than cognitive rescue. These results demonstrate that LLMs can serve as in silico test benches for exploring candidate digital biomarkers and clinical training protocols, while highlighting architectural constraints that may inform computational hypotheses about memory and language processing. Full article

Background: Gastric biopsy remains central to diagnosing Helicobacter pylori infection, autoimmune gastritis, intestinal metaplasia, dysplasia, and gastric cancer. However, morphology-based assessment is limited by interobserver variability, sampling constraints, and an incomplete ability to capture molecular heterogeneity and predict progression. Objective: This mini review summarizes how multi-omics technologies and artificial intelligence (AI) are modernizing gastric biopsy diagnostics, enabling precision classification, risk stratification, and workflow improvement. Methods: A narrative synthesis was undertaken across key literature on gastric pathology, multi-omics (genomics, transcriptomics, epigenomics, proteomics, lipidomics, metabolomics, microbiomics, and spatial approaches), and AI in endoscopy and computational pathology. Results: Multi-omics profiling enhances mechanistic understanding and refines disease classification by capturing clonal evolution, pathway dysregulation, immune–microenvironment interactions, and metabolic remodeling, with potential for biomarker discovery and therapy prediction. AI applications demonstrate strong performance across the gastric diagnostic pathway, including improved lesion detection during endoscopy, reduced miss rates, lesion segmentation, classification of precancerous conditions, H. pylori recognition, and near-expert histopathology classification. Evidence from systematic reviews supports robust diagnostic accuracy, while prospective studies highlight real-time feasibility. Conclusions: Integrating AI with multi-omics is shifting gastric biopsy from descriptive histology toward data-driven precision gastroenterology. Key barriers include dataset quality, standardization, interpretability, cost, and regulatory and ethical governance; addressing these will be essential for routine clinical adoption. Full article

Background/Objectives: Mathematical modelling provides a quantitative way to describe the fate and action of drugs in the oral cavity, where transport processes are shaped by salivary flow, pellicle formation, biofilm structure and the wash-out effect of gingival crevicular fluid (GCF). Local pharmacokinetics in the mouth differ substantially from systemic models, and therefore a dedicated framework is required. The aim of this work was to present a structured, physiologically based concept that links in vitro release testing with local pharmacokinetics and pharmacodynamics. Methods: A narrative review with elements of systematic search was conducted in PubMed, Scopus and Web of Science (1980–2025) for publications describing drug release, local PBPK, and PK/PD modelling in the oral cavity. Mathematical formulations were grouped into release kinetics, mini-PBPK transport and local PK/PD relations. Classical models (Higuchi, Korsmeyer–Peppas, Peppas–Sahlin) were integrated with a mini-PBPK structure describing saliva–mucosa–biofilm–pocket interactions. Results: The combined model captures adsorption to pellicle, diffusion within biofilm and wash-out by GCF. It allows simulation of variable clinical conditions, such as inflammation-related changes in Q_GCF, and links local exposure to pharmacodynamic outcomes. Case studies with PerioChip^®, Arestin^®, and Atridox^® demonstrate how mechanistic models explain observed therapeutic duration and low-systemic exposure. Conclusions: The proposed mini-PBPK framework bridges empirical release data and physiological transport in the oral cavity. It supports rational formulation design, optimisation of local dosage, and personalised prediction of drug retention in gingival pockets. This modelling approach can become a practical tool for the development of dental biomaterials and subgingival therapies. Full article