Search Results (1,777)

Background/Objectives: The Bicêtre score for Vein of Galen Aneurysmal Malformation (VGAM) relies on existing end-organ damage. We hypothesized that transthoracic echocardiography (TTE) could quantify significant systemic steal in clinically stable neonates (Bicêtre score ≥ 12). This study evaluates the Aortic Flow Reversal Ratio (AoFRr) as a tool to measure this steal and predict treatment outcomes. Methods: In a single-center retrospective study of patients with VGAM, the AoFRr (the ratio of the diastolic reversal velocity time integral to the systolic forward volume time integral) was calculated via TTE in the abdominal aorta at the level of the diaphragm before and after endovascular embolization. Over the study period, the cohort underwent a total of 30 endovascular interventions and 49 TTEs. Pre-intervention AoFRr was correlated with the Bicêtre score, and post-intervention changes were analyzed for association with the need for subsequent embolizations. Results: In a cohort of 12 patients with a median Bicêtre score of 18, 83.3% had pre-intervention aortic diastolic flow reversal. The median pre-intervention AoFRr was 0.81, indicating substantial systemic steal despite clinical stability. A post-intervention AoFRr reduction of ≥85% was significantly associated with a lower likelihood of requiring re-intervention (p = 0.0253). Conclusions: The AoFRr quantifies substantial hemodynamic steal in VGAM patients who appear clinically stable by the Bicêtre score. Its reduction following embolization predicts a more favorable clinical course. The AoFRr is a valuable, non-invasive adjunct for risk stratification and may help optimize the timing of endovascular intervention. Full article

Harnessing nature’s ingenuity with microorganisms for industrial production is an attractive solution to today’s climate concerns. Nature’s innate diversity allows the production of many value-added chemicals and can be expanded on through genetic engineering. Although the use of microbial cell factories (MCFs) has been extremely successful at lab scale, the numbers of successful bioprocesses remain limited. High cell densities and long cultivation times lead to reductions in productivity over the course of the cultivation through the effects of genetic and expression instability of the strain. This instability leads to population diversification. In this review, we explore the roots of genetic instability in microorganisms, focusing on prokaryotic bioprocesses, and how organisms cope with this instability. We spotlight single-cell detection methods capable of monitoring populations within the bioprocess both in- and on-line. We also examine different approaches to minimizing population diversification, both through strain development and bioprocess engineering. With this review, we highlight the fact that population-averaged metrics overlook the single-cell stresses driving genetic and functional instability, leading to an overestimation of microbial bioprocess robustness. High-throughput single-cell monitoring in industry-like conditions remains essential to identify and select truly stable microbial cell factories and bioprocesses. Full article

Background/Objectives: Infections due to multidrug-resistant (MDR) Acinetobacter baumannii represent a critical challenge in modern healthcare, with limited therapeutic options. Eravacycline, a novel fluorocycline antibiotic, demonstrates promising in vitro activity, but real-world clinical data for complex intra-abdominal infections (IAIs) are scarce. We present two cases of severe IAI caused by carbapenem-resistant A. baumannii (CRAB) successfully treated with eravacycline. Methods: We describe the clinical course, microbiological findings, and outcomes of two critically ill patients. Case 1 was a 75-year-old male with biliary peritonitis following an endoscopic procedure. Case 2 was a 64-year-old male with infected pancreatic walled-off necrosis. Both patients had cultures positive for CRAB and failed multiple prior antibiotic regimens. Results: In both cases, the initiation of intravenous eravacycline led to significant clinical improvement, including resolution of septic shock and defervescence. A marked reduction in inflammatory markers (C-reactive protein and procalcitonin) was observed, alongside microbiological clearance of CRAB. Eravacycline was well tolerated, with no significant adverse events. Conclusions: These case reports suggest that eravacycline can be an effective and safe salvage therapy for complex IAIs caused by CRAB, even in scenarios of partial source control. It represents a valuable addition to the antimicrobial armamentarium for managing infections caused by these extensively drug-resistant organisms. Full article

With the advancement of artificial intelligence and educational informatization, there is a growing demand for intelligent teaching assistance systems in universities. Focusing on the university “Algorithms” course in the computer science department, this study develops a multi-terminal collaborative knowledge service system, Course-Oriented Knowledge Service–Based AI Teaching Assistant System (CKS-AITAS), which consists of a PC terminal and a mobile terminal, where the PC terminal integrates functions including knowledge graph, semantic retrieval, intelligent question-answering, and knowledge recommendation. While the mobile terminal enables classroom check-in and teaching interaction, thus forming a closed-loop platform for teaching organization, resource acquisition, and knowledge inquiry. For the document retrieval module, paragraph-level semantic modeling of textbook content is conducted using Word2Vec, combined with approximate nearest neighbor indexing, and this module achieves an MRR@10 of 0.641 and an average query time of 0.128 s, balancing accuracy and efficiency; the intelligent question-answering module, based on a self-built course FAQ dataset, is trained via the BERT model to enable question matching and answer retrieval, achieving an accuracy rate of 86.3% and an average response time of 0.31 s. Overall, CKS-AITAS meets the core teaching needs of the course, provides an AI-empowered solution for university teaching, and boasts promising application prospects in facilitating education sustainability. Full article

Oesophageal cancer remains a significant global health burden with poor survival outcomes despite multimodal treatment. Recent advances in magnetic resonance imaging (MRI) have opened opportunities to improve radiotherapy delivery. This review examines the role of MRI and MR-guided radiotherapy (MRgRT) in oesophageal cancer, focusing on applications in staging, treatment planning, and response assessment, with particular emphasis on magnetic resonance linear accelerator (MR-Linac)-based delivery. Compared to computed tomography (CT), MRI offers superior soft-tissue contrast, enabling more accurate tumour delineation and the potential for reduced treatment margins. Real-time MR imaging during treatment can facilitate motion management, while daily adaptive planning can accommodate anatomical changes throughout the treatment course. Functional MRI sequences, including diffusion-weighted and dynamic contrast-enhanced imaging, offer quantitative data for treatment response monitoring. Early clinical and dosimetric studies demonstrate that MRgRT can significantly reduce radiation dose to critical organs while maintaining target coverage. However, clinical evidence for MRgRT in oesophageal cancer is limited to small early-phase studies, with no phase II/III trials demonstrating improvements in survival, toxicity, or patient-reported outcomes. Long-term clinical benefits and cost-effectiveness remain unproven, highlighting the need for prospective outcome-focused studies to define the role for MRgRT within multimodality treatment pathways. Full article

Background: Sinonasal neuroendocrine carcinoma (SNEC) is an extremely rare malignancy, and, to date, no clinical reports have detailed the use of proton beam therapy (PBT) for this disease. The present study describes the clinical courses of patients with SNEC treated with PBT and highlights the advantages of PBT. Methods: In this retrospective study, we included patients with pathologically confirmed SNEC without distant metastasis who underwent PBT at our institution between 2006 and 2021. To evaluate the dosimetric advantages of PBT, comparative treatment plans using VMAT were created. Result: Six patients with pathologically diagnosed SNEC without distant metastasis were treated with PBT. Multimodal treatment was applied in five patients, including chemotherapy in four cases and surgery in two cases. The median follow-up period was 37.4 months (range: 6.9 to 108.9 months). At the end of the follow-up, three patients were alive without recurrence, while three had died due to the disease. Recurrence occurred in three cases: one local recurrence, one in cervical lymph nodes, and two distant metastases. A late adverse event of Grade 4 vision decrease was observed in one patient on the ipsilateral side. Compared with VMAT, PBT lowered the average brain dose (median 3.3 Gy (RBE) vs. 12.6 Gy), brainstem D2 cc (10.7 Gy (RBE) vs. 34.9 Gy) and contralateral optic nerve D0.1 cc (47.6 Gy (RBE) vs. 63.3 Gy), while doses to the ipsilateral optic pathway were comparable. Conclusions: PBT in multimodal treatment achieved feasible local control for SNEC. The dose-sparing effect of PBT was more evident in organs distant from the target, although careful consideration is required for adjacent structures. Full article

Introduction: Sarcoidosis is a systemic granulomatous disorder classified among interstitial lung diseases (ILDs). While the lungs and intrathoracic lymph nodes are most affected, the disease can involve multiple organs. The heterogeneity of clinical presentation arises from complex interactions between environmental exposures and immune responses in genetically susceptible individuals. Sex-dependent genetic variations are associated with differences in phenotype and organ localization. Gender-related factors also influence the impact of sarcoidosis on quality of life and health perception, contributing to variability in disease burden and outcomes. Aim of the study: to provide an overview of sex- and gender-related differences in sarcoidosis, focusing on pathophysiological and clinical implications. Material and Methods: The systematic search was conducted on Medline database through Pubmed search engine. We included all clinical studies from 1992 to the present, and imposed language restrictions, accepting only English publications. Case reports, reviews, and pre-print studies were excluded. Results: A total of 35 studies were included. Sex differences significantly influenced both age of onset and clinical presentation of the disease. Women received a diagnosis of sarcoidosis at an older age and exhibited more frequently extrapulmonary localizations, with predominant involvement of the eyes, skin, and extra-thoracic lymph nodes. In contrast, men more commonly presented with limited pulmonary forms. Löfgren syndrome was more prevalent among women and appeared to be associated with sex-specific genetic variations, particularly within the MHC region. Gender differences also impacted quality of life and disease perception: women reported a lower quality of life and were more susceptible to anxiety and depression throughout the disease course. Conclusions: This report confirms that clinical presentation of sarcoidosis is significantly influenced by sex and gender. The identification of sex- and gender-specific clinical patterns supports a personalized medicine framework, in which diagnostic assessment, monitoring strategies, and therapeutic approaches may be tailored according to individual biological and gender-related characteristics. Full article

Pembrolizumab, an anti-PD-1 monoclonal antibody, showed promising results in the treatment of different types of solid tumors and generally an improvement in overall survival and patients’ outcome. However, as a drug that targets the immune system to enhance the anti-tumor response, it simultaneously increases the risk of autoimmune reactions, producing immune-related adverse events (irAEs). These irAEs might involve any body organ, and in some cases may lead to treatment discontinuation. In this article, we discuss two cases of triple-negative breast cancer (TNBC) patients, who developed irAEs during the course of neoadjuvant pembrolizumab, highlighting the mechanism of the reactions, possible clinical manifestations, and potential management. Full article

Ventilator-associated pneumonia (VAP) remains the most frequent ICU-acquired infection and a major driver of antimicrobial exposure. Historically, clinicians treated patients for 10–14 days or longer, particularly when multidrug-resistant organisms were suspected. Current evidence from randomized trials and meta-analyses now supports shorter-course therapy (~7 days) for most immunocompetent patients with VAP who demonstrate clinical improvement. Mortality and treatment failure are not increased when compared with longer regimes. The REGARD-VAP trial demonstrated the non-inferiority of individualized ≤7-day therapy compared with conventional longer courses. This remained true even in cohorts rich in non-fermenting Gram-negative bacilli (NF-GNB) and carbapenem-resistant organisms while markedly reducing antibiotic-related toxicity. North American and European guidelines recommend 7–8 days as the default duration, with individualized extension for slow clinical response, bacteremia, uncontrolled foci, or profound immunosuppression. Additionally, biomarker-guided discontinuation, particularly serial procalcitonin (PCT), may reduce antibiotic days when used to enrich clinical assessment. This narrative review synthesizes guideline recommendations, trial evidence, biomarker-guided stewardship, and pathogen- and patient-specific scenarios to provide a practical framework for intensivists: treat until infection is controlled and the patient is improving, usually about 1 week, and extend therapy only with clear justification. Full article

Preterm birth has evolved from being an acute neonatal challenge to a lifelong health determinant, as advances in neonatal care have markedly improved the survival of very and extremely preterm infants. This narrative review synthesizes epidemiological and mechanistic evidence linking preterm birth with heightened cardiometabolic risk across the life course. In adulthood, individuals born preterm demonstrate increased rates of heart failure, ischemic heart disease, stroke, atrial fibrillation, and diabetes. Beneath these overt clinical outcomes lies a distinct phenotype characterized by increased adiposity, insulin resistance, dyslipidemia, hypertension, and atypical growth trajectories, with rapid catch-up growth amplifying long-term risk. Mechanistic pathways highlight adipose tissue maldevelopment, predisposing to metabolic syndrome, alongside cardiac maldevelopment with reduced ventricular size, impaired diastolic function, and diminished exercise capacity. Furthermore, vascular growth arrest, impaired elastin synthesis, and nephron deficiency contribute to sustained elevations in blood pressure, establishing an early substrate for hypertension and cardiovascular remodeling. These alterations reflect the developmental origins of health and disease, whereby early-life disruption of growth and maturation exerts lasting effects on organ structure and function. Collectively, the evidence identifies adults born preterm as a growing yet under-recognized patient population with a unique clinical and biochemical profile and accelerated vulnerability to non-communicable diseases. Greater awareness among pediatric and adult physicians, structured transition of care, and targeted prevention strategies are urgently needed to mitigate early cardiometabolic morbidity and optimize long-term health outcomes in this high-risk group. Full article

Objectives: Non-A Non-B (NANB) aortic dissections (ADs) are uncommon. Because of their rarity, their therapeutic pathway is not yet standardized, and anatomic or goal-directed treatments are not reported in current practices. We reviewed the treatment strategies of NANB AD across Europe, aiming to identify factors associated with increased mortality and the need for intervention, outlining optimal management pathways for future care. Methods: This multicentre cohort study was carried out in four European aortic centres, retrospectively including patients affected by NANB AD over the last 10 years. Patients’ anatomical clinical and treatment data were collected with the aim of investigating the factors associated with their need for intervention and increased mortality, comparing the characteristics of those requiring surgery with those who responded to medical treatment alone. Results: Thirty-eight NANB patients (26, 68.4% men; mean age 60.6 ± 12.87) were included. The primary entry tear was identified in Ishimaru zone 1 or 2 in most cases (24, 63.2%) and the dissection extended distally to the ilio-femoral arteries in half of the patients (21, 55.3%). Surgical repair was indicated in 21 (55.3%) cases within 90 days of acute onset for end-organ ischemia, impending aortic rupture, or retrograde extension of the dissection (including 11 emergent/urgent operations), with most patients requiring surgery within 15 days of acute onset (17, 44.7%). The mean aortic diameter among patients requiring surgery was significantly higher in both zone 1 (7 37 IQR 3 versus 34 IQR 7, p = 0.043) and 2 (36 IQR 6 versus 32.5 IQR 7, p = 0.044) when compared with patients who underwent medical treatment alone. An increased in-hospital mortality rate was noted among patients with indication for surgery after medical treatment (0% versus 30.8%, p = 0.023). Conclusions: This cohort provides an additional description of clinical aspects and current practices in the treatment of NANB in Europe. Most patients of this series had an indication for surgery within two weeks of acute onset, demonstrating a frequently complicated course; moreover, this raises questions surrounding the most appropriate timing for interventional management. Although a diameter threshold was not identified, the baseline enlarged aortic diameter in zones 1 and 2 seemed to be associated with a need for early intervention. Further study is needed to fully refine the indications for treatment in NANB patients; this will support the study of the independent risk factors for increased mortality risk and complications among this group, and will allow the identification of subgroups of patients that may benefit from more aggressive treatment from acute onset. Full article

The Cyber Kill Chain (CKC) is a prevalent concept in cyber defense; nevertheless, its emphasis on post-reconnaissance phases limits the capacity to foresee attacker activities outside the organizational boundary. This study introduces and empirically substantiates a pre-chain phase, referred to as contextual anticipation, which broadens the temporal framework of the CKC by methodically identifying subtle yet actionable signals prior to reconnaissance. The methodology combines the STEMPLES+ framework for socio-technical scanning with General Morphological Analysis (GMA), generating internally coherent scenarios that are translated into Indicators of Threats (IOT). These indicators connect contextual triggers to threshold-based monitoring activities and established courses of action, forming a reproducible and auditable relationship between foresight analysis and operational defense. The application of three illustrative cases—a banking merger, the distribution of a phishing kit in underground marketplaces, and wartime contribution scams—illustrated that contextual anticipation consistently provided quantifiable lead-time benefits varying from several days to six weeks. This proactive stance enabled measures such as registrar takedowns, targeted awareness campaigns, and anticipatory monitoring before distribution and exploitation. By formalizing CKC-0 as an integrated socio-technical phase, the research enhances cybersecurity practice by demonstrating how diffuse contextual drivers can be converted into organized, actionable mechanisms for proactive resilience. Full article

Citizen science approaches for monitoring, and even restoring, coral reefs have grown in popularity though tend to be restricted to those who have taken courses that expose them to the relevant methodologies. Now that cheap (~10 USD), waterproof pouches for smart phones are widely available, there is the potential for mass acquisition of coral reef images by non-scientists. Furthermore, with the emergence of better machine-learning-based image classification approaches, high-quality data can be extracted from low-resolution images (provided that key benthic organisms, namely corals, other invertebrates, & algae, can be distinguished). To determine whether informally captured images could yield comparable ecological data to point-intercept + photo-quadrat surveys conducted by highly proficient research divers, we trained an artificial intelligence (AI), CoralNet, with images taken before and during a bleaching event in 2015 in Chagos (Indian Ocean). The overall percent coral covers of the formal, “gold standard” method and the informal, “tourist diver” approach of 38.7 and 35.1%, respectively, were within ~10% of one another; coral bleaching percentages of 30.5 and 31.8%, respectively, were statistically comparable. Although the AI was prone to classifying bleached corals as healthy in ~one-third of cases, the fact that these data could be collected by someone with no knowledge of coral reef ecology might justify this approach in areas where divers or snorkelers have access to waterproof cameras and are keen to document coral reef condition. Full article

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by progressive fibrosis and immune dysregulation, with lung involvement being a major cause of morbidity and mortality. Type V collagen (COLV), a cryptic self-antigen, has been implicated in the pathogenesis of fibrosis in both SSc and lung allograft dysfunction. To characterize the early histological, molecular, and immunological events associated with lung remodeling following immunization with COLV in a murine model (IMU-COLV), and to establish a temporal framework for fibrosis progression. Using a time-course design, lung tissue from IMU-COLV mice was analyzed at multiple intervals post-immunization. Histopathological assessment, immunohistochemistry, and gene expression analysis were performed to evaluate inflammation, endothelial activation, extracellular matrix remodeling, and collagen composition. We observed a progressive and spatially organized pattern of lung remodeling, beginning with peribronchovascular immune infiltration and culminating in airway-centered fibrosis. These changes were accompanied by dynamic endothelial activation, increased expression of profibrotic markers, and alterations in collagen architecture particularly involving COLV. The remodeling pattern closely mirrors histological features observed in early SSc-associated interstitial lung disease and other fibrotic conditions, such as idiopathic pulmonary fibrosis and chronic lung allograft dysfunsion. The IMU-COLV model recapitulates key early features of SSc-related lung fibrosis, highlighting COLV’s potential role as a driver of immune-mediated tissue remodeling. These findings provide a valuable platform for investigating the mechanisms underlying fibrogenesis and for testing targeted interventions in the early phases of pulmonary fibrosis. Full article

Background/Objectives: Antimicrobial resistance (AMR) in ocular infections has become a serious concern with major implications for vision preservation. Bacterial AMR contributed to 4.71 million deaths worldwide in 2021, and ophthalmology mirrors these trends with multidrug resistance rates as high as 66% documented in some regions and persistently high methicillin resistance among common ocular pathogens. Across regions and care settings, traditional empiric therapies are losing effectiveness against an expanding range of pathogens, resulting in slower recovery, more complications, and, in many cases, permanent vision loss. This review aims to synthesize recent clinical, microbiologic, and pharmacologic evidence on ocular AMR, focusing on recent studies to capture current resistance patterns, therapeutic challenges, and evolving management strategies. Methods: Most included papers were published between 2020 and 2025, with additional foundational studies referenced where appropriate. Reports and systematic reviews addressing bacterial, viral, fungal, and parasitic ocular pathogens were evaluated to characterize current resistance mechanisms and management strategies across ocular pathogens. Results: The eye’s anatomic and physiologic barriers limit drug penetration, often promoting resistance and reducing therapeutic efficacy. Resistance mechanisms vary by pathogens; Pseudomonas keratitis is driven mainly by efflux pumps and biofilm formation, while CMV retinitis’ mutations in UL97 and UL54 are linked with clinical failure, and in MRSA associated Staphylococcus keratitis, the presence of mecA necessitates vancomycin-based therapy across bacterial, viral, fungal, and parasitic infections, with mechanisms such as β-lactamase production, efflux pump overexpression, target-site mutation, and biofilm formation contributing to poor response to standard therapy. MDR Pseudomonas keratitis remains the leading cause of rapidly progressive corneal infection with high risk of perforation and vision loss, while resistant CMV retinitis continues to threaten sight in immunocompromised patients despite antiviral advances. MDR organisms are recalcitrant to treatment and may lead to longer treatment courses and potentially worse outcomes and are discussed in detail within the manuscript. Conclusions: Ocular AMR represents an urgent and expanding clinical challenge. This review centers on the two most encountered multidrug-resistant organisms and their corresponding ocular sites, Pseudomonas aeruginosa (anterior segment) and CMV (posterior segment), while contextualizing them within the broader spectrum of resistant bacterial, viral, fungal, and parasitic pathogens. Despite growing awareness of AMR in ophthalmology, comprehensive surveillance data and longitudinal epidemiologic studies remain limited, making it difficult to track evolving resistance trends or guide region-specific therapy. Preserving vision in the AMR era will require faster diagnostics, improved ocular drug-delivery systems, and pathogen-specific therapies. Full article