Predicting warming impacts on pollinators is key for understanding and preserving biodiversity and ecosystem services under climate change. In the tropics, where most species exist, insect pollination is essential for functioning forests. However, the vulnerability of tropical insect pollinators such as bees to climate change is understudied. Existing studies lack links between thermal physiological metrics to pollination services. We quantified physiological heat tolerance, behavioural thermoregulation abilities, and their links to species role played in flower-visitation network for a tropical native bee community across different seasons. Physiological tolerance from 708 individuals of 92 bee species revealed strong phylogenetic signals and Halictidae exhibited ~3 ℃ lower heat tolerance than other bees in the hot-dry season when heat stress is the highest. Further quantification of body temperatures revealed Halictidae also had weaker ability to maintain stable body temperatures. Analyzing extensively sampled networks showed specialization index of bees, which is associated with pollination efficacy, was negatively correlated with heat tolerance in the hot-dry season. Specialized Halictidae interactions are therefore potentially more vulnerable to temperature rises, potentially leading to increasingly dominant generalized interactions in the future under climate change.

Cathepsins are a family of lysosomal proteases which function in several biological processes such as protein degradation, tissue remodeling, immune response and progression of cancer. Among humans, there exist a group of 15 cathepsins with names ranging from Cathepsin A to Cathepsin Z which are examined here in this review for their structure, function and therapeutic perspectives. The Protein Data Bank (PDB) was used to acquire the human cathepsin 3D structures and modeled with AlphaFold2, a state-of-the art deep learning-based method. We explain what the specificities among cathepsin subtypes are for preferred substrates and target organs and include their implication in pathological diseases such as cancer and osteoporosis. In addition, we review the latest research on cathepsin inhibitors as potential therapeutic targets for various human diseases. This review aims to provide an updated and comprehensive understanding of human cathepsins and their potential applications in medicine.

A significant proportion of adults diagnosed with ADHD also exhibit emotional dysregulation (ED) in addition to the core symptoms of the condition. However, ADHD-associated ED is neither consistently conceptualised nor taken into account diagnostically. Furthermore, the distinction between patients with ADHD who do and do not also exhibit ED remains ambiguous. Research has demonstrated that individuals diagnosed with ADHD exhibit unstable EEG-based regulation of their brain arousal. In contrast, individuals diagnosed with depression exhibit stable brain arousal regulation in the EEG. In light of these findings, we have formulated a hypothesis that an additional ED may influence brain arousal regulation in individuals with ADHD, thereby resulting in measurable differences in the EEG. EEG data were collected at a specialized outpatient clinic for adult ADHD of our department. Data were analyzed retrospectively by an EEG-based algorithm (VIGALL 2.1) assessing brain arousal. There was no difference in brain arousal between ADHD subgroups with or without ED. A more severe symptomatology in the ADHD with ED subgroup was observed. ED is a common symptomatic domain in ADHD contributing to a more severe symptomatology. The identification of a consensus on the concept of ED and the development of an operationalisation based on specific questionnaires could facilitate the establishment of a foundation for further studies. The brain arousal regulation model provides insights into the aetiology of ED, paving the way for further investigations into clinical subgrouping and targeted treatments.

Global change is complex and multidimensional, making it challenging to understand how human activities affect ecosystem processes. A critical gap in this understanding is how drivers of global change broadly affect food webs. While an industry of studies documents shifts in energy pathways within food webs in response to anthropogenic pressures, a synthesis that links these shifts to structural and functional changes in food webs is lacking. To address this, we review studies across diverse ecosystems that use stable isotope analysis, energetic food web modelling, and gut content analysis to reveal the prevalence of asymmetric rewiring---a phenomenon whereby anthropogenic pressures differentially impact habitats across space, altering some energy pathways relative to others. We then highlight several examples from the literature to illustrate how this process unfolds. To explore its broader consequences, we use a simple food web model to demonstrate how asymmetric rewiring alters resilience and key ecosystem functions, such as primary and secondary production. Our synthesis uncovers a remarkably general response in food web structure to global environmental change that needs to be better understood to protect nature and the services that human societies rely on in a rapidly changing world.

The background of Takotsubo cardiomyopathy is classically associated with identifiable emotional stress; however, there is a significant number of cases that meet the diagnostic criteria without any identifiable antecedent stress. While the literature reports cases of Takotsubo cardiomyopathy triggered by various factors such as emotional stress or physical stress, our case highlights a unique association between steroid and Takotsubo Cardiomyopathy (TCM). In this instance, we present a rare case involving a 72-year-old family patient with a medical history significant for immune thrombocytopenia (ITP) and coronary artery disease status post-stent placement in the left anterior descending artery 16 years ago in 2009. The patient presented with cardiac chest pain, and while cardiac catheterization ruled out coronary artery disease, the left ventricle gram strongly suggested Takotsubo cardiomyopathy, a diagnosis later confirmed by a surface echocardiogram. Interestingly, the patient denied recent catastrophic events causing stress but revealed that the patient was taking 40mg of dexamethasone for five days for ITP management.

This paper presents a comprehensive theoretical and experimental framework review probing the dark sector through Higgs boson decay events (H → γγ) at the ATLAS detector, interpreted within the Superluminal Graviton Condensate Vacuum (SGCV) model. The SGCV framework suggests the existence of superluminal, massless dark photons-transient imprints of displaced vacuum gravitons-that traverse spacetime faster than light (v DP > c) before converting into observable Standard Model photons. These transitions give rise to measurable time-of-flight anomalies (∆t) and spatial origin displacements (∆x) in detector systems. To empirically test these predictions, we propose an experimental configuration featuring sub-picosecond Timeof-Flight (ToF) instrumentation and synchronized vertex timing to identify such anomalies with high statistical confidence. A simulation framework modeling the distribution of ToF deviations is developed, and detector sensitivity thresholds are analyzed across a range of plausible path geometries. The SGCV model also connects to the Dodecahedron Linear String Field Hypothesis (DLSFH), enabling a scalehybrid description of vacuum structure that incorporates both chaotic graviton dynamics and compactified string field behavior. Our results suggest that the detection of dark photon intermediaries in collider environments would provide compelling evidence for non-luminal propagation signatures and a quantized vacuum structure testable through collider-based precision timing experiments. This work opens a new frontier in experimental quantum gravity, linking collider anomalies, vacuum topology, and high-energy astrophysical observations within a unified phenomenological framework. Disclaimer: All phenomenological results and figures presented in this work are derived from theoretical modeling and simulation. No actual detector data from ATLAS, SHiP, or other experiments are used in this paper.

Background: Sickle Cell Disease (SCD) is a genetic disorder in which red blood cells undergo episodes of sickling following hypoxemia. Episodes of ischaemic crisis in children are predicted to accelerate the decline in pulmonary function. There are few published reports on lung function assessments in children with sickle-cell disease in sub-Saharan Africa. This study aimed to investigate the association between patterns of spirometry assessment in children with SCD in Ghana. Method: A case-control study involving 115 children aged 6-16 years with SCD and 115 non-SCD controls was carried out at the Komfo Anokye Teaching Hospital. Demographic, socio-economic, and clinical information were collected. Spirometry was performed for 130 cases and controls at enrolment. Results: Children with SCD had lower lung volumes and lower anthropometric measurements compared to the controls: forced expiratory volume in 1 second (FEV 1), cases vs controls, 1.40L vs 1.80L, (p<0.001), forced vital capacity (FVC), cases vs controls,1.70L vs 2.10L, (p<0.001), body mass index(BMI), cases vs controls,16.0 kg/m 2 vs 17.2 kg/m 2, (p= 0.002), height, cases vs controls, 135cm vs 143cm, (p<0.001) weight, cases vs controls, 31kg vs 38kg, (p<0.001). Restrictive abnormality on spirometry was predominant, 43% (n=49) in cases compared to 25% (n=29) in controls. Obstructive abnormality was uncommon. We observed an association between older age and restrictive pattern on spirometry (OR 1.53, 95% CI 1.23-21.91, p <0.001) as well as BMI and restrictive pattern on spirometry (OR 0.63, CI 0.48-0.81, p<0.001) Conclusion: This study has demonstrated a predominance of low anthropometric measurements and restrictive abnormality on spirometry in children with SCD in Ghana. Restrictive pulmonary function abnormality is associated with older age and lower BMI.

Introduction: Pulmonary embolism (PE) is a rare, but serious condition in children. Clinical Guidelines for imaging a suspected pediatric PE, in Pediatric Emergency Medicine [PEM] are lacking. The computerized Tomography Pulmonary Angiogram (CTPA) is the preferred diagnostic modality for suspected PE in an emergency room. Our study aims to introduce a simplified clinical assessment-based tool for ordering CTPA in children in an emergency room setting. Methods: This is a retrospective review of patients managed in our Emergency Department from 2000 to 2020. Patients were identified based on the International Classification of Disease codes related to PE, deep vein thrombosis, or similar diagnoses. The control group was patients with symptoms of PE, seen in the same time frame as the study group, who had negative CTPA. Results: Twenty-five CTPA-positive patients were identified. Twenty three of 25 CTPA positive patients were between 13 to 18 years old. Common risk factors included here are protein-losing state i.e. nephrotic syndrome. Others include oral contraceptive pill use, and obesity. Chest pain and tachypnea were the most common complaint and clinical sign, respectively. Hypercoagulability screen was negative in 65% of the patients. The mean D-dimer was 5.27 g/ml, and 6 patients—of whom 4 had saddle PE—had D-dimer > 10. Reoccurrence of PE and neuro-deficits was noted in 2 patients each. Conclusion: We present clinical criteria for ordering CTPA in children with suspected PE, based on data from our center, and a literature review of pediatric studies. Further multicentric studies, with larger samples, are needed to validate our suggested criteria.

Adverse drug reactions (ADRs) can lead to severe consequences and increased morbidity and mortality rates. Phenobarbital is one of the most common anti-epileptic drugs that has numerous adverse drug reactions, including toxic epidermal necrolysis. The event is rare and a medical emergency. A six year-old female epileptic child with phenobarbital induced toxic epidermal necrolysis referred for the management of diffuse exfoliative lesions involving her eyes and buccal mucosa. Associated with the skin lesions, the patient reported high grade fever, reddish eye discoloration, dysphagia and dry cough. The exfoliative skin lesion involved ninety percent of her total body surface area. The patient was managed with withdrawal of phenobarbital, IV antibiotics, systemic corticosteroid, twice daily wound care, analgesic and nutritional support. Early recognition, discontinuation of offending medications, and prompt intervention are crucial to mitigate harm. Raising awareness about ADRs and their management is vital for enhancing patient safety and outcomes.

Objective: This study aimed to evaluate the accuracy, consistency, and reliability of three large language models—ChatGPT-4.0, DeepSeek-R1, and Gemini-2.0—in answering cervical cancer-related questions based on the ESGO/ESTRO/ESP guidelines. Design: Prospective, comparative in silico benchmarking study. Setting: Fondazione Policlinico Universitario A. Gemelli, Italy. Population or Sample: Fifty questions derived from the ESGO/ESTRO/ESP Guidelines for Cervical Cancer. Methods: Each question was submitted simultaneously to ChatGPT-4.0, DeepSeek-R1, and Gemini-2.0, and re-entered twice to assess response repeatability. Answers were evaluated for accuracy using a Global Quality Score (GQS) from 1 (poor) to 5 (completely accurate). Consistency (intra-model response stability) and reliability (alignment with guidelines) were assessed using binary classification. Main Outcome Measures: Mean GQS, percentage of GQS 5 responses, consistency between repeated answers, and reliability. Results: ChatGPT-4.0 achieved the highest performance, with 42% of responses rated GQS 5, followed by Gemini-2.0 (30%) and DeepSeek-R1 (28%). DeepSeek-R1 scored significantly lower in mean GQS (3.02 ± 1.671) compared to ChatGPT-4.0 (3.74 ± 1.411, p=0.022). Response consistency varied significantly, with ChatGPT-4.0 and DeepSeek-R1 showing differences from Gemini-2.0 (p=0.034 and p=0.044, respectively). No significant difference was observed in reliability (p=0.602). Conclusion: All three models showed suboptimal accuracy in applying cervical cancer guidelines. ChatGPT-4.0 was the most accurate and consistent, while DeepSeek-R1 underperformed. Despite similar reliability across models, expert oversight remains essential to ensure safe clinical application and prevent misinformation. Funding: None.

One of the most deadly types of cancer is skin cancer, especially melanoma; early discovery is very important to increase survival rates. Handmade feature extraction, a crucial component of conventional approaches for skin cancer classification, may face constraints due to irrelevant patterns and background noise. Although deep learning models such as convolutional neural networks (CNNs) have shown potential in medical imaging, they often lack interpretability and suffer from data shortages. Attention Enhanced Convolution Net (AECNet) is a hybrid attention-based CNN model proposed in this work to improve feature learning by concentrating on pertinent areas of skin cancer images, hence raising classification accuracy. We used an Auxiliary Classifier Generative Adversarial Network (ACGAN) to create synthetic images, thereby improving the generalizing capacity of the model in order to solve data shortage. We also incorporated Grad-CAM Explainable AI (XAI) methods to offer visual explanations of the model's decision-making process, hence enhancing its clinical relevance and interpretability. Using synthetic images, findings show notable increases in classification accuracy, precision, recall, and F1-score; the model achieves a test accuracy of 95.63%. Apart from improving the accuracy of skin cancer diagnosis, the suggested method offers a more open and understandable structure for clinical uses.

Epigenetic modifications, particularly DNA methylation, are increasingly recognized as mechanisms underlying phenotypic plasticity and potential mediators of transgenerational responses to environmental change. We investigated the persistence of early life temperature-induced DNA methylation changes and the role of parental life history in shaping methylation patterns in juvenile brown trout (Salmo trutta). Fertilized eggs from crosses of anadromous and resident trout were incubated under natural or elevated temperatures (by +3°C) until first feeding, after which all fish were reared under common conditions. Whole-genome bisulfite pooled sequencing was conducted on juveniles 10.5 months post-fertilization. We found weak and inconsistent evidence for persistent temperature-induced methylation changes, with little overlap among different parental cross types. In contrast, parental life history, particularly maternal origin, significantly influenced offspring methylation patterns. Maternally derived differences were more extensive than paternal effects and were enriched for genes related to metabolism, nervous system function, and digestion, suggesting potential adaptive relevance. These findings highlight a limited long-term impact of early-life thermal conditions on methylation and emphasize a stronger role of transgenerational epigenetic effects in brown trout. Given that climate change is expected to alter thermal regimes in future aquatic ecosystems, our results, along with other recent publications, suggest that parental environmental history may be a more significant driver of epigenetic variability than temperature experienced during eary life. Understanding such mechanisms is critical for predicting how populations may respond to ongoing and future climate change.

Complete Resolution of Cutaneous Leishmaniasis with a Novel Topical Combination Therapy: A Case Series

Key Clinical MessageOseltamivir, a medication commonly used to treat influenza, is rarely associated with the development of neuropsychiatric symptoms. This case report describes a 59-year-old male with no past psychiatric medical history who developed acute anxiety, palpitations, and other neuropsychiatric symptoms following oseltamivir treatment for influenza. It emphasizes the need for vigilance in monitoring patients for these potential associated symptoms.

Background: Understanding patient’s attitudes towards deprescribing is important for implementation of deprescribing in practice. These attitudes may differ within a patient depending on the medication. Objective: To assess whether there are within-patient differences in attitudes towards deprescribing the following cardiovascular and diabetes medications: statins, antihypertensives, sulfonylureas and insulins. Methods: We administered the revised Patient Attitudes Towards Deprescribing questionnaire to Dutch primary care patients. The ‘appropriateness’ and ‘concerns’ subscales were adapted to measure medication-specific attitudes. Pairwise comparisons of unreversed appropriateness and concerns sum scores were tested with Wilcoxon signed-rank tests, and differences in underlying items were explored. Results: Out of 280 patients that completed the questionnaire, 160 patients (median age: 79 years, 34% frail) did so for at least two medication classes. Patients’ perceived deprescribing of their insulins less appropriate as compared to the other medication classes (all p<.031), and deprescribing sulfonylureas less appropriate as compared to antihypertensives (p=.036) or statins (p=.006). No differences were found for the concerns sum scores but differences were observed in underlying items. Conclusion: Patients were more positive towards deprescribing statins and antihypertensives as compared to sulfonylureas and particularly insulins. Healthcare providers should be aware that patients can experience medication-specific barriers when discussing options for deprescribing.

A document by Reza Jafari. Click on the document to view its contents.

not-yet-known not-yet-known not-yet-known unknown The hair types of stipe, rachis, costae, fronds and indusia of 15 species of Hypodematium from China have been carefully observed and photographed under anatomical microscope and scanning electron microscope (SEM) for the first time. The results show that the species can be divided into tree groups based on their rod-shaped glandular hairs and non-glandular hairs under SEM: 1) H. sinense K. Iwatsuki and H. fordii (Bak.) Ching with rod-shaped glandular hairs; 2) H. crenatum (Forssk.) Kuhn, H. hirsutum (Don) Ching, H. guilinense J. X. Li & X. J. Li and H. zhangii J. X. Li & X. J. Li with non-glandular hairs; 3) H. confertivillosum J. X. Li, F. Q. Zhou & X. J. Li, H. squamuloso-pilosum Ching, H. mengshanensis J. X. Li & X. J. Li, H. shandongense J. X. Li & X. J. Li, H. gracile Ching, H. glanduloso-pilosum (Tagawa) Ohwi, H. jianxiuii X. J. Li, H. chingii J. X. Li & X. J. Li and H. taishanensis J. X. Li. & X. J. Li with rod-shaped glandular hairs and non-glandular hairs. These characteristics were stable within species but show significant differences between species, which is combined with palynology, these results not only provide new data of submicroscopic structure characteristics for the species identification and systematic classification for the first time, but also provide a basis for studying the biodiversity of Hypodematium, which is of great significance for the exploitation and conservation of its resources.

Background: The anatomical and immunological parallels between cervical and anal canals raise questions about shared HPV pathogenesis. This study evaluates the concordance of HPV/cytology between sites and their association with histopathology. Methods: We retrospectively analyzed 984 women undergoing concurrent cervical/anal cytology and HPV testing (Jan, 2019–Jun, 2024). Subgroups included 706 with colposcopy and 265 with HRA histopathology. Consistency was assessed using chi square tests, Cramér’s V, and diagnostic performance metrics. Results: HPV-16 dominated both sites (cervix: 27.54%; anus: 21.44%). Cervical-anal cytology showed weak-moderate agreement (Cramér’s V=0.225, p <0.001), while HPV genotyping demonstrated stronger concordance (V=0.458, p <0.001), especially for HPV-16/18 (60%, 180 anal positive in 300 cervical positive). Histopathology correlation was weak (Spearman’s ρ=0.261). Anal HPV predicted anal LSIL+ poorly (PPV=43.7%, AUC=0.55). Combined anal HPV/LCT screening improved sensitivity (89.2%) but reduced specificity (22.1%). Conclusion: While cervical and anal HPV infections are moderately associated, site-specific variations in cytology and histopathology necessitate independent clinical evaluation.

Based on the CiteSpace Software tool, this article specifically analyzed the research development process and the current research status in the field of Feeder Automation from 1981 to 2024 with 1,892 papers from the core collection of Web of Science. This article adopted the methods of Knowledge Graph, from the external feature analysis, co-citation analysis, and research hotspot and frontier analysis to analyze the research status of foremost research scholars, primary cited literature, and significant research hotspots in the field of Feeder Automation in various aspects, to sort out the current research status of the field, and reveal the future research hotspots and directions in the field.

At a time of economic turmoil and accelerated technological change, the resilience and sustainability of organizations and cities are put to the test like never before. The paper presents a study on how a more interdependent use of three strategic enablers, Artificial Intelligence (AI), Internet of Things (IoT) and Data Science (DS), can be linked to improve adaptive capacity in turbulence economies. Utilizing recent empirical works and theoretical perspectives (Haque et al., 2024a) on adaptive leadership (business), AI-based optimization (nonprofit & finance sectors) (Faruq et al., 2024; Haque et al., 2024e), IoT (manufacturing supply chain) (Al-Samad et al., 2024) and smart city solutions (Sufian et al., 2024), this paper advocates an intricate paradigm of technological resilience. These findings identify success factors, barriers, and ethical considerations, offering practical insights for policymakers, managers, and technologists seeking to navigate complexity and promote sustainable development.

not-yet-known not-yet-known not-yet-known unknown The Sri Lankan leopard (Panthera pardus kotiya), an endemic subspecies and the apex predator, meets significant conservation uncertainties stemming from habitat degradation and intensifying human-leopard interactions in unprotected regions. This study examines the preying patterns of leopards residing in the human dominated tea estate landscapes of the Upper Kelani River Basin (UKRB), in the Central Highlands of Sri Lanka to evaluate prey composition, diversity, and the balance between wild and domestic prey. Analysis of 107 scat samples indicated a wide-ranging diet of the Sri Lankan leopard consisting of 17 prey species, primarily wild animals, with the black-naped hare (Lepus nigricollis) being the most commonly ingested prey. Biomass research revealed the significant prey biomass contribution from medium-sized prey, such as barking deer (Muntiacus malabaricus), whereas domestic species comprised less than 15% of the diet. Analysis of prey selectivity utilizing Jacob’s Index indicated a predilection for specific prey species such as the large-sized prey of sambar (Rusa unicolor), and the small and easy prey of domestic cats (Felis catus), underscoring the leopards’ adaptation to available resources. These findings highlight the leopards’ ecological adaptability and the necessity of preserving prey diversity to facilitate coexistence in anthropogenically transformed environments. Conservation proposals comprise habitat restoration, educational initiatives, and integrated management measures to reduce conflict and promote leopard survival in fragmented habitats.

Exhaled breath condensate (EBC), a non-invasive biofluid that captures biomarkers from airway surface fluid, offers novel avenues for pathophysiological research and clinical management of respiratory and systemic diseases. Despite advancements in sample collection and detection, clinical translation remains hindered by critical challenges: inconsistent biomarker standardization leads to cross-study data variability, and the absence of miniaturized equipment limits real-time and portable monitoring. This review systematically synthesizes key EBC research domains: biomarker classification encompasses small molecules, inflammation-related proteins, and pathogens. Collection methods have evolved from passive cooling (e.g., R-Tube) to active strategies (Dynamic temperature control, inertial impact). Detection technologies leverage nanomaterials and microfluidics to achieve picogram-level sensitivity, shifting from single-analyte tests to multi-omics integration for comprehensive disease mechanism analysis. Wearable applications progress from proof-of-concept laboratory prototypes to scenario-specific designs, such as smart masks enabling real-time epidemic screening and continuous biomarker monitoring. A novel aspect of this review is its highlighting of EBC research as a ”technology cluster,” emphasizing the interdisciplinary integration of electrochemical, biotechnological, and AI-driven innovations alongside rigorous clinical validation. This framework addresses translational bottlenecks, positioning EBC as a transformative precision medicine tool enabling early disease screening, personalized diagnostics, and non-invasive dynamic monitoring—thereby bridging the divide between research and clinical practice.

Background: The effectiveness of the Enhanced Recovery After Surgery (ERAS) protocol in elective cesarean deliveries (CD) is well established. Its applicability and safety in emergency CD remain unclear and require further investigation. Objective: This study aimed to evaluate postoperative recovery in pregnant women who underwent emergency CD. The recovery process was assessed using the Quality of Recovery questionnaire (QoR-35, Thai version) and pain scores measured by the Visual Analog Scale (VAS), comparing the modified ERAS (mERAS) protocol to the standard protocol. Materials and Methods: Fifty pregnant women were enrolled in a randomized controlled trial conducted at the medical education center of Phayao Hospital. The primary outcomes were the 24-hour QoR-35 score and the 48-hour VAS score. Additional parameters, including postoperative hospitalization duration, opioid use, and the onset of gastrointestinal functions, were also assessed. The analysis further considered postoperative complications such as fever, wound dehiscence, and readmission. Results: The mERAS group showed a significant reduction in 48-hour postoperative VAS scores (mean (SD): 4.0 (1.7) vs. 5.0 (1.3); mean difference: 1.0, 95% CI 0.14, 1.86, p = 0.024). No significant differences were observed between the two groups in assessments conducted at 24 hours or immediately postoperatively across all parameters. The mERAS group experienced shorter hospitalization (p = 0.017), earlier onset of burping (p = 0.049), and earlier onset of flatulence (p = 0.011). Neither group required additional opioid administration or experienced postoperative complications such as fever, wound dehiscence, or readmission. Conclusion: The implementation of a modified ERAS protocol effectively reduced VAS pain scores within 48 hours postoperatively, shortened hospitalization duration, and improved patient outcomes without increasing morbidity or surgical complications in patients undergoing emergency cesarean delivery.

Background Infective endocarditis (IE) is a serious condition that damages the heart valves and leads to complications such as heart failure, blood clots, and stroke. It is the third most common fatal infection worldwide. This review explores the clinical burden of IE, its causative microbes, and the challenges associated with its diagnosis. The study aims to assess the limitations of traditional blood cultures and highlight the potential of metagenomics in identifying a broader range of pathogens, particularly culture-negative and fastidious organisms. Methods A comprehensive review of the literature was conducted, focusing on diagnostic methodologies for IE, including traditional blood cultures, molecular techniques, and metagenomic approaches. The role of biofilms in treatment failure and the mechanisms of antibiotic resistance within biofilms were also examined. Results Metagenomics was identified as a promising tool for improving IE diagnosis by overcoming the limitations of culture-based methods. The review highlights the potential of cell-free metagenomic DNA (cf-mDNA) as a non-invasive diagnostic approach. Additionally, biofilms were found to play a crucial role in treatment failure due to their protective environment, which enhances antibiotic resistance. Conclusion Metagenomic approaches show great promise in enhancing the diagnosis of infective endocarditis. However, standardized protocols and guidelines are necessary to optimize their clinical application. Further prospective studies are required to validate the clinical significance of metagenomics in the diagnosis and treatment of IE.