Search Results (8,834)

As an emerging threat to global food security, wheat blast necessitates the development of a rapid and field-deployable detection system to facilitate early diagnosis, enable effective management, and prevent its further spread to new regions. In this study, we aimed to validate and improve a Recombinase Polymerase Amplification coupled with PCRD lateral flow detection (RPA-PCRD strip assay) kit for the rapid and specific identification of Magnaporthe oryzae pathotype Triticum (MoT) in field samples. The assay demonstrated exceptional sensitivity, detecting as low as 10 pg/µL of target DNA, and exhibited no cross-reactivity with M. oryzae Oryzae (MoO) isolates and other major fungal phytopathogens under the genera of Fusarium, Bipolaris, Colletotrichum, and Botrydiplodia. The method successfully detected MoT in wheat leaves as early as 4 days post-infection (DPI), and in infected spikes, seeds, and alternate hosts. Furthermore, by combining a simplified polyethylene glycol-NaOH method for extracting DNA from plant samples, the entire RPA-PCRD strip assay enabled the detection of MoT within 30 min with no specialized equipment and high technical skills at ambient temperature (37–39 °C). When applied to field samples, it successfully detected MoT in naturally infected diseased wheat plants from seven different fields in a wheat blast hotspot district, Meherpur, Bangladesh. Training 52 diverse stakeholders validated the kit’s field readiness, with 88% of trainees endorsing its user-friendly design. This method offers a practical, low-cost, and portable point-of-care diagnostic tool suitable for on-site genomic surveillance, integrated management, seed health testing, and quarantine screening of wheat blast in resource-limited settings. Furthermore, the RPA-PCRD platform serves as an early warning modular diagnostic template that can be readily adapted to detect a wide array of phytopathogens by integrating target-specific genomic primers. Full article

Background/Objectives: Keratoconus, a condition in which the cornea becomes thinner and steeper, can cause visual problems, particularly when it is progressive. Early diagnosis is important for preserving visual acuity. Raw data, unlike preprocessed data, are unaffected by software modifications. They retain their native structure across versions, providing consistency for analytical purposes. The objective of this study was to design a deep learning-based graphical user interface for predicting the corneal ectasia score using raw optical coherence tomography data. Methods: The graphical user interface was developed using Tkinter, a Python library for building graphical user interfaces. The user is allowed to select raw data from the cornea/anterior segment optical coherence tomography Casia2, which is generated in the 3dv format, from the local system. To view the predicted corneal ectasia score, the user must determine whether the selected 3dv file corresponds to the left or right eye. Extracted optical coherence tomography images are cropped, resized to 224 × 224 pixels and processed by the modified EfficientNet-B0 convolutional neural network to predict the corneal ectasia score. The predicted corneal ectasia score value is displayed along with a diagnosis: ‘No detectable ectasia pattern’ or ‘Suspected ectasia’ or ‘Clinical ectasia’. Performance metric values were rounded to four decimal places, and the mean absolute error value was rounded to two decimal places. Results: The modified EfficientNet-B0 obtained a mean absolute error of 6.65 when evaluated on the test dataset. For the two-class classification, it achieved an accuracy of 87.96%, a sensitivity of 82.41%, a specificity of 96.69%, a PPV of 97.52% and an F1 score of 89.33%. For the three-class classification, it attained a weighted-average F1 score of 84.95% and an overall accuracy of 84.75%. Conclusions: The graphical user interface outputs numerical ectasia scores, which improves other categorical labels. The graphical user interface enables consistent diagnostics, regardless of software updates, by using raw data from the Casia2. The successful use of raw optical coherence tomography data indicates the potential for raw optical coherence tomography data to be used, rather than preprocessed optical coherence tomography data, for diagnosing keratoconus. Full article

American tegumentary leishmaniasis (ATL) and other infectious granulomatous diseases (IGDs) may present with oral/oropharyngeal mucosal lesions (OOPML). IGD-OOPML can result from fungal, parasitic, or bacterial infections, and squamous cell carcinoma (SCC) represents the main differential diagnosis. ATL, other IGD, and SCC share overlapping clinical and epidemiological features, making diagnostic suspicion challenging. This study compared sociodemographic and clinical characteristics among ATL, other IGD, and SCC. Descriptive, comparative, and multivariable logistic regression analyses were performed. Among 7551 patients, 213 met inclusion criteria (83-SCC and 130-IGD). Except for smoking, which differed only between ATL and SCC, most IGD parameters were similar. Male patients predominated in all groups. SCC patients were significantly older (p < 0.001) and had a shorter median disease duration (p = 0.007). The presence of pain increased the odds of SCC-OOPML by 3.96 times (95% CI 1.97–12.51). SCC patients were more likely to present lesions in a single subsite, either the oral cavity or oropharynx. Painful, ulcerated, or exophytic lesions favored SCC diagnosis, whereas infiltrative, granular, or mulberry-like lesions, involvement of multiple subsites, or associated nasal and laryngeal lesions suggested IGDs. Although clinical differentiation remains difficult, these findings may support early diagnostic suspicion, prompt treatment, and reduced sequelae. Full article

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that utilizes magnetic fields to induce cortical electric currents, enabling both the measurement and modulation of neuronal activity. Initially developed as a diagnostic tool, TMS now serves dual roles in clinical neurology, offering insight into neurophysiological dysfunctions and the therapeutic modulation of abnormal cortical excitability. This review examines key TMS outcome measures, including motor thresholds (MT), input–output (I/O) curves, cortical silent periods (CSP), and paired-pulse paradigms such as short-interval intracortical inhibition (SICI), short-interval intracortical facilitation (SICF), intracortical facilitation (ICF), long interval cortical inhibition (LICI), interhemispheric inhibition (IHI), and short-latency afferent inhibition (SAI). These biomarkers reflect underlying neurotransmitter systems and can aid in differentiating neurological conditions. Diagnostic applications of TMS are explored in Parkinson’s disease (PD), dystonia, essential tremor (ET), Alzheimer’s disease (AD), and mild cognitive impairment (MCI). Each condition displays characteristic neurophysiological profiles, highlighting the potential for TMS-derived biomarkers in early or differential diagnosis. Therapeutically, repetitive TMS (rTMS) has shown promise in modulating cortical circuits and improving motor and cognitive symptoms. High- and low-frequency stimulation protocols have demonstrated efficacy in PD, dystonia, ET, AD, and MCI, targeting the specific cortical regions implicated in each disorder. Moreover, the successful application of TMS in differentiating and treating AD and MCI underscores its clinical utility and translational potential across all neurodegenerative conditions. As research advances, increased attention and investment in TMS could facilitate similar diagnostic and therapeutic breakthroughs for other neurological disorders that currently lack robust tools for early detection and effective intervention. Moreover, this review also aims to underscore the importance of maintaining standardized TMS protocols. By highlighting inconsistencies and variability in outcomes across studies, we emphasize that careful methodological design is critical for ensuring the reproducibility, comparability, and reliable interpretation of TMS findings. In summary, this review emphasizes the value of TMS as a distinctive, non-invasive approach to probing brain function and highlights its considerable promise as both a diagnostic and therapeutic modality in neurology—roles that are often considered separately. Full article

Background: Obstructive sleep apnea is characterized by recurrent upper airway obstruction during sleep, leading to intermittent hypoxemia, sleep fragmentation, and excessive daytime sleepiness. Affecting up to 11% of the adult Polish population and more commonly diagnosed in men, OSA poses a major public health concern due to its association with cardiovascular, metabolic, and neurocognitive complications. This review summarizes the current evidence on diagnostic methods, risk factors, and therapeutic approaches, with particular emphasis on oral appliance therapy using mandibular advancement devices (MADs). Methods: A systematic literature review was conducted using the PubMed and Scopus databases, covering publications from 2020 to 2025, including clinical trials, meta-analyses, and systematic reviews evaluating the efficacy and safety of MAD therapy. Results: Findings demonstrate that MAD effectively reduces apnea–hypopnea index (AHI) values, improves oxygen saturation, and alleviates snoring and daytime fatigue, offering a patient-tolerable alternative for those intolerant to continuous positive airway pressure (CPAP). However, long-term use may cause occlusal or dental changes. Novel techniques, such as Er:YAG laser therapy, show potential in treating mild OSA. Moreover, epidemiological data suggest a correlation between tooth loss and an increased risk of OSA, particularly among men over 65. Conclusions: Dentists play a pivotal role in early detection, screening, and interdisciplinary management of OSA, underscoring the importance of collaboration between dental professionals and sleep medicine specialists for comprehensive care. Full article

Heart sound-based detection of cardiovascular diseases is a critical task in clinical diagnostics, where early and accurate identification can significantly improve patient outcomes. In this study, we investigate the effectiveness of combining traditional acoustic features and transformer-based Wav2Vec embeddings with advanced machine learning models for multi-class classification of five heart sound categories. Ten engineered acoustic features, i.e., Log Mel, MFCC, delta, delta-delta, chroma, discrete wavelet transform, zero-crossing rate, energy, spectral centroid, and temporal flatness, were extracted as regular features. Four model configurations were evaluated: a hybrid CNN + LSTM and XGBoost trained with either regular features or Wav2Vec embeddings. Models were assessed using a held-out test set with hyperparameter tuning and cross-validation. Results demonstrate that models trained on regular features consistently outperform Wav2Vec-based models, with XGBoost achieving the highest accuracy of 99%, surpassing the hybrid model at 98%. These findings highlight the importance of domain-specific feature engineering and the effectiveness of ensemble learning with XGBoost for robust and accurate heart sound classification, offering a promising approach for early detection and intervention in cardiovascular diseases. Full article

Background and Clinical Significance: Prader–Willi syndrome (PWS) is an imprinting disorder not typically associated with severe congenital sensorineural hearing loss (SNHL). When profound SNHL is present in an infant with a known syndrome, an independent monogenic etiology should be considered. We report the first molecularly confirmed case of PWS co-occurring with biallelic pathogenic TMC1 variants causing congenital SNHL, outlining diagnostic challenges, cochlear implant (CI) outcomes, and implications for blended phenotypes. Case Presentation: A male infant with PWS due to a paternal 15q11.2–q13 deletion failed newborn hearing screening. Diagnostic auditory brainstem response and auditory steady-state response confirmed bilateral severe-to-profound SNHL. Temporal bone CT/MRI were normal. Comprehensive genetic testing identified compound heterozygous TMC1 variants consistent with autosomal recessive DFNB7/11 hearing loss, plus two variants of uncertain significance in SERPINB6 and EPS8L2. Sequential bilateral cochlear implantation was performed (left ear at 14 months, right at 20 months), followed by auditory–verbal therapy. Over four years, the child showed steady improvements in hearing and early-speech development. Conclusions: Early genomic evaluation is essential when clinical features appear atypical for a known syndrome. Identifying TMC1-related deafness enabled timely cochlear implantation and measurable gains. This case highlights that severe congenital SNHL in a syndromic infant may reflect a distinct monogenic disorder rather than phenotypic expansion of the primary syndrome, emphasizing the importance of recognizing blended phenotypes to guide precision-care strategies in rare disorders. Full article

Background/Objectives: Emotional dysregulation (ED) is emerging as a major contributor to functional impairment in Autism Spectrum Disorder (ASD). Although effective behavioral interventions exist, pharmacological treatments remain constrained by side effects and variable tolerability. Given their neurobiological roles that include neurotransmission, inflammation, and neuroplasticity, vitamin D and omega-3 polyunsaturated fatty acids (PUFAs) have been identified as promising candidates for modulating emotional and behavioral dysregulation. This systematic review aimed to evaluate the efficacy of combined vitamin D and omega-3 supplementation in improving emotional and behavioral regulation in individuals with ASD. Methods: This review was conducted in accordance with PRISMA guidelines. Included studies were English peer-reviewed studies involving participants with ASD that assessed combined vitamin D and omega-3 suppleupplementation with outcomes related to emotional or behavioral dysregulation. The search was restricted to 2015–2025 to ensure inclusion of recent, methodologically consistent studies and to minimize heterogeneity in diagnostic criteria and supplementation protocols. Results: Of 649 records initially screened, 3 studies met inclusion criteria: one randomized controlled trial, one observational study, and one case report, involving participants ranging from early childhood to young adulthood. Across studies, combined supplementation was associated with improvements in irritability, hyperactivity, agitation, and self-injurious behaviors. These clinical effects were accompanied by specific biochemical changes, including reductions in the AA/EPA ratio, increases in serum 25(OH)D and omega-3 indices, and decreased urinary levels of HVA and VMA. Conclusions: This review indicates that co-supplementation with vitamin D and omega-3 fatty acids may exert preliminary beneficial effects on emotional and behavioral dysregulation in individuals with ASD, potentially through anti-inflammatory and neuroregulatory mechanisms. However, the available evidence remains limited due to a small number of studies, their modest sample size, and methodological heterogeneity. Further, biomarker-driven randomized studies are needed to confirm efficacy and delineate optimal dosing strategies for application in clinics. Full article

Baseline plasma ACTH concentrations are frequently utilized as part of the diagnostic evaluation of equids when PPID is suspected. Baseline ACTH can be impacted by many factors including time of year, i.e., ACTH has generally been found to be elevated during late summer through early autumn in the northern hemisphere. An understanding of ACTH concentrations in healthy equids over the course of a year is useful for the proper interpretation of concentrations in PPID-suspect animals. Previous studies assessing ACTH concentrations in healthy donkeys (Equus asinus) and hybrids (E. asinus x E. caballus) are limited, often utilizing very small numbers, equids from specific and limited geographical regions, limited timeframes or unspecified donkey types (miniature, standard, or mammoth). We aimed to characterize the seasonal variation in baseline ACTH concentrations in healthy miniature donkeys, standard donkeys and hybrids in the United States (US) and to compare those concentrations across these groups. Following outlier removal, 19 standard donkeys (from California (CA), Massachusetts (MA), New York (NY)), 14 miniature donkeys (CA and NY), and 28 hybrids (Texas (TX) and NY) were utilized for analysis. Samples were collected from each equid twice per month from June to November 2019 and once per month from December 2019 through May 2020. The mean ACTH concentration of all equids was higher from mid-August through the end of October compared to the rest of the year (being the highest in the second half of September with the mean (standard deviation) values of 109.6 (52.6), 134.6 (67.4), and 100.8 (189.6) in standard donkeys, miniature donkeys, and hybrids, respectively). Additionally, ACTH concentrations in hybrids were 23% (95% Confidence Interval (CI): 4–38%) and 51% (95% CI: 36–63%) lower than in standard and miniature donkeys, respectively, from mid-August through October. During the rest of the year, hybrids similarly showed 31% (95% CI: 16–43%) and 30% (95% CI: 15–42%) lower ACTH concentrations compared with standard and miniature donkeys, respectively. Full article

Background and Clinical Significance: Overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) in children is a rare but life-threatening metabolic emergency. The coexistence of hyperosmolality and ketoacidosis increases neurologic vulnerability and complicates fluid and insulin management. Early identification and osmolality-guided therapy are essential to prevent cerebral edema and other complications. This case describes a 5-year-old boy with new-onset type 1 diabetes mellitus (T1D) presenting with DKA/HHS overlap two weeks after influenza vaccination—an unusual temporal association without proven causality. Case Presentation: A previously healthy 5-year-old presented with progressive polyuria, polydipsia, nocturnal enuresis, fatigue, and drowsiness. Two weeks earlier, he had received the influenza vaccine. Examination revealed moderate dehydration without Kussmaul respiration or altered consciousness. Laboratory evaluation showed glucose 45.9 mmol/L (826 mg/dL; reference 3.9–7.8 mmol/L), venous pH 7.29 (reference 7.35–7.45), bicarbonate 12 mmol/L (reference 22–26 mmol/L), moderate ketonuria, and measured serum osmolality 344 mOsm/kg (reference 275–295 mOsm/kg), fulfilling diagnostic criteria for DKA/HHS overlap. After an initial 20 mL/kg 0.9% NaCl bolus, fluids were adjusted to maintenance plus approximately 10% deficit using 0.45–0.75% NaCl according to sodium/osmolality trajectory. Intravenous insulin (approximately 0.03–0.05 IU/kg/h) was initiated once blood glucose no longer decreased adequately with fluids alone and had stabilized near 22.4 mmol/L (≈400 mg/dL). Dextrose was added when glucose reached 13.9 mmol/L (250 mg/dL) to avoid rapid osmolar shifts. Hourly neurological and biochemical monitoring ensured a glucose decline of 2.8–4.2 mmol/L/h (50–75 mg/dL/h) and osmolality decrease ≤3 mOsm/kg/h. The patient recovered fully without cerebral edema or neurologic sequelae. IA-2 antibody positivity with low C-peptide and markedly elevated HbA1c confirmed new-onset T1D. Conclusions: This case highlights the diagnostic and therapeutic challenges of pediatric DKA/HHS overlap. Osmolality-based management, conservative insulin initiation, and vigilant monitoring are crucial for preventing complications. The temporal proximity to influenza vaccination remains incidental. Full article

Liver fibrosis, the progressive accumulation of scar tissue resulting from chronic liver disease, is increasingly recognized as a multi-system condition, the effects of which extend beyond the liver, affecting brain health. Dementia, characterized by progressively impaired cognition sufficient to impede daily functioning, is a major global health issue with incompletely defined risk factors and pathogenic precursors. To examine the relationship between liver fibrosis and cognitive outcomes, we conducted a comprehensive PubMed literature search, and human studies published in English were included. Evidence is synthesized on the pathophysiology and clinical significance of liver fibrosis, types of dementia, and studies supporting the association between liver fibrosis and cognitive impairment. Meta-analytic data indicate that liver fibrosis is associated with an approximately 30% increased risk of incident dementia (pooled hazard ratio ~1.3), with progressively higher risks across more advanced fibrosis stages. Putative pathomechanisms, potentially modulated by age and sex, include chronic systemic and neuro-inflammation, insulin resistance, vascular dysfunction, and a perturbed intestinal microbiota–liver–brain axis. Non-invasive liver fibrosis diagnostics, advanced neuroimaging, and biomarkers represent key tools for assessing risk. In conclusion, liver fibrosis is a systemic condition that can affect brain health. Early detection, thorough risk assessment and interventions, such as lifestyle changes, metabolic therapies, and antifibrotic treatments, may help protect neural function. Key research gaps are identified, with suggestions for improving understanding of liver fibrosis’s connection to dementia or cognitive impairment. Full article

Background/Objectives: Early and accurate characterization of endometrial cancer (EC) is crucial for patient management, but current imaging modalities lack in diagnostic accuracy and ability to assess molecular profiles. The aim of this study is to evaluate hybrid [¹⁸F]FDG PET/MRI’s diagnostic accuracy in EC staging and role in predicting tumor aggressiveness, molecular characterization, and recurrence. Methods: A prospective study (ClinicalTrials.gov, ID:NCT04212910) evaluating EC patients undergoing [¹⁸F]FDG PET/MRI before surgery (2018–2024). Histology, immunohistochemistry, and patients’ follow-up (mean FU time: 3.13y) were used as the reference standard. [¹⁸F]FDG PET/MRI, PET only, and MRI only were independently reviewed to assess the diagnostic accuracy (ACC), sensitivity (SN), specificity (SP), and positive/negative predictive value (PPV, NPV). Imaging parameters were extracted from [¹⁸F]FDG PET and pcT1w, T2w, DWI, and DCE MRI. Spearman’s correlations, Fisher’s exact test, ROC-AUC analysis, Kaplan–Meier survival curves, log-rank tests and Cox proportional hazards models were applied. Results: Eighty participants with primary EC (median age 63 ± 12 years) were enrolled, with 17% showing LN involvement. [¹⁸F]FDG PET/MRI provided ACC = 98.75%, SN = 98.75%, and PPV = 100% for primary tumor detection, and ACC = 92.41%, SN = 84.62%, SP = 93.94%, PPV = 73.33%, and NPV = 96.88% for LN detection. PET/MRI parameters predicted LN involvement (AUC = 79.49%), deep myometrial invasion (79.78%), lymphovascular space invasion (82.00%), p53abn (71.47%), MMRd (74.51%), relapse (82.00%), and postoperative administration of adjuvant therapy (79.64%). Patients with a tumor cranio-caudal diameter ≥ 43 mm and MTV ≥ 13.5 cm³ showed increased probabilities of recurrence (p < 0.001). Conclusions: [¹⁸F]FDG PET/MR showed exceptional accuracy in EC primary tumor and LN detection. Derived parameters demonstrated potential ability in defining features of aggressiveness, molecular alterations, and tumor recurrence. Full article

Background: MiRNAs have emerged as minimally invasive biomarkers with considerable potential for the early detection of oral squamous cell carcinoma (OSCC). Although numerous studies have evaluated circulating miRNAs across different biofluids, the comparative diagnostic performance of saliva-, serum-, and plasma-derived miRNAs has not been systematically clarified. Methods: A meta-analysis was performed by screening PubMed, MEDLINE, Scopus, CINAHL, and related databases. Nineteen eligible studies evaluating miRNA-based assays in saliva, serum, or plasma were included. A random-effects bivariate model was used to calculate pooled sensitivity, specificity, and area under the HSROC curve. Meta-regression using log diagnostic odds ratio (lnDOR) examined whether biofluid type significantly influenced diagnostic performance. Results: Salivary miRNAs showed a pooled sensitivity of 0.76 (95% CI: 0.68–0.82; I² = 84.69%), specificity of 0.79 (95% CI: 0.70–0.85; I² = 70.41%), and an AUC of 0.84 (95% CI: 0.80–0.87). Plasma miRNAs produced comparable results with a pooled sensitivity of 0.77 (95% CI: 0.61–0.88; I² = 90.45%), specificity of 0.79 (95% CI: 0.63–0.89; I² = 80.20%), and an AUC of 0.85 (95% CI: 0.81–0.89). Serum-derived miRNAs demonstrated the highest accuracy with a pooled sensitivity of 0.82 (95% CI: 0.70–0.90; I² = 76.92%), specificity of 0.88 (95% CI: 0.75–0.95; I² = 74.87%), and an AUC of 0.91 (95% CI: 0.89–0.94). Despite serum’s numerically superior performance, meta-regression revealed no significant matrix effect (Wald χ² = 0.20, p = 0.903). Conclusions: Although serum-derived miRNAs performed best overall, biofluid type was not a statistically significant determinant of diagnostic performance. Full article

Background/Objectives: Kidney cancer (RC) is a significant global health burden. Renal cell carcinoma (RCC) is the most common form of kidney cancer. Its predominant histological subtype is clear cell renal cell carcinoma (ccRCC), which is frequently diagnosed at an advanced local stage or with metastases. Detecting cancer at an early stage significantly increases the likelihood of a cure; therefore, research on new markers and a thorough understanding of tumor biology are essential. This study investigated the significance of aromatase (ARO), cathepsin S (CTSS), and matrix metalloproteinase 1 (MMP-1) as potential biomarkers in ccRCC. Methods: ARO, CTSS, and MMP-1 concentrations in plasma were determined using SPRi biosensors. Appropriate antibodies were used as biorecognition molecules in the biosensors. The samples analyzed came from 60 patients with histopathologically confirmed clear cell renal cell carcinoma (ccRCC) and from 26 patients diagnosed with chronic cystitis or benign prostatic hyperplasia (BPH). Results: A statistically significant increase (p < 0.00001) in the concentration of all proteins compared with the control samples was observed at the T3–T4 stage. The ARO concentration was already statistically significantly higher at the T1–T2 stage (p < 0.00001). The ROC curve for aromatase demonstrated high sensitivity and specificity for detecting ccRCC, with a cut-off point of 7.53 ng mL⁻¹. A moderate positive correlation was also found between the concentrations of the three tested substances in renal cancer, which may indicate potential interactions in the tumor’s pathogenesis. Conclusions: SPRI testing has been shown to be an alternative to standard methods for detecting potential ccRCC markers. The biosensors used in the study can simultaneously determine ARO, CTSS, and MMP-1. The results obtained suggest the potential importance of these proteins in the development of ccRCC, and our work proposes a new diagnostic technique that may aid in the diagnosis of ccRCC. Full article

Endometriosis is traditionally conceptualized as a pelvic lesion–centered disease; however, mounting evidence indicates it is a chronic, systemic, and multifactorial inflammatory disorder. This review examines the molecular dialog between ectopic endometrial tissue, the immune system, and peripheral organs, highlighting mechanisms that underlie disease chronicity, symptom variability, and therapeutic resistance. Ectopic endometrium exhibits distinct transcriptomic and epigenetic signatures, disrupted hormonal signaling, and a pro-inflammatory microenvironment characterized by inflammatory mediators, prostaglandins, and matrix metalloproteinases. Immune-endometrial crosstalk fosters immune evasion through altered cytokine profiles, extracellular vesicles, immune checkpoint molecules, and immunomodulatory microRNAs, enabling lesion persistence. Beyond the pelvis, systemic low-grade inflammation, circulating cytokines, and microRNAs reflect a molecular spillover that contributes to chronic pain, fatigue, hypothalamic–pituitary–adrenal axis dysregulation, and emerging gut–endometrium interactions. Furthermore, circulating biomarkers—including microRNAs, lncRNAs, extracellular vesicles, and proteomic signatures—offer potential for early diagnosis, patient stratification, and monitoring of therapeutic responses. Conventional hormonal therapies demonstrate limited efficacy, whereas novel molecular targets and delivery systems, including angiogenesis inhibitors, immune modulators, epigenetic regulators, and nanotherapeutics, show promise for precision intervention. A systems medicine framework, integrating multi-omics analyses and network-based approaches, supports reconceptualizing endometriosis as a systemic inflammatory condition with gynecologic manifestations. This perspective emphasizes the need for interdisciplinary collaboration to advance diagnostics, therapeutics, and individualized patient care, ultimately moving beyond a lesion-centered paradigm toward a molecularly informed, holistic understanding of endometriosis. Full article