Search Results (2,609)

This study investigates the extreme wave event that caused damage to the main breakwater at Chancay Port, Peru, on 24 August 2025 (the 824 event), through high-resolution nested numerical wave simulations. The research reveals the underlying mechanisms and causation of the damage. Results indicate that the extreme waves originated from a powerful storm in the Southern Pacific’s Roaring Forties around 20 August. The storm generated long-period swell that propagated to Chancay Port, resulting in significant wave heights of 4.2–4.4 m offshore, exceeding the 475-year return period design standard and ranking as the most severe wave event in the past 30 years. Localized modeling further demonstrates that the swells induced nonlinear transformations in front of the breakwater, with wave heights reaching up to 7 m along the structure and generating complex standing waves near the bend. Comprehensive analysis concludes that the damage was caused by the combined effects of this rare extreme remote swell and localized hydrodynamic interactions with the breakwater. Full article

Background: Hypermobile Ehlers–Danlos syndrome (hEDS) can present as a complex interplay of widespread symptomatology and multisystem involvement, posing diagnostic and treatment challenges. Objective characterization of cervical spine and neurovascular findings in hEDS has been limited. Previous studies have emphasized upper cervical spine complications in hEDS, yet the relevance and mechanisms underlying associated symptomatology have not been elucidated. This study examined objective test findings in patients with hEDS at an outpatient neck clinic to explore cervical spine and neurovascular pathology that could contribute to further understanding the clinical profile of a subset of patients with hEDS. Methods: This single-center, retrospective observational study included patients with hEDS aged 20–50 years from 1 January 2022–31 December 2024, at an outpatient neck center. It excluded previous neck surgery, traumatic events, or related injury. Demographic, clinical, and diagnostic data were collected through a retrospective chart review, including measurements from standard clinical diagnostic protocols: digital motion X-ray (videofluoroscopy), cone beam CT, Doppler ultrasound, and tonometry. Results: More than 71% of patients reported ≥29 symptoms. Nearly all patients exhibited co-occurring forward head, decreased depth of curve, ligamentous cervical instability, and decreased internal jugular vein (IJV) and vagus nerve cross-sectional area (CSA). Vagus nerve CSA was found to be significantly smaller than the comparative healthy/normal population. IJV CSA was significantly smaller at C1 than at C4–C5, suggesting evidence of carotid sheath compression at C1. Conclusions: This study offers novel evidence that cervical spine pathology, IJV compression, and vagus nerve degeneration are uniformly prevalent in hEDS, which may contribute to, or be an etiological basis for, the multisystem involvement in a subset of patients with this disorder. These findings provide hypothesis-generating data to inform future mechanistic and therapeutic studies, including exploration of new diagnostic and treatment targets. Full article

Background and Objectives: Evidence on the impact of adherence to the Mediterranean diet alone—without supplementation—on serum and follicular fluid fatty acid profiles and assisted reproduction outcomes remains limited. This study evaluated the effects of a pre-treatment Mediterranean diet intervention on these parameters. Materials and Methods: In this prospective, non-randomized controlled trial, 32 women undergoing infertility treatment were allocated to a Mediterranean diet intervention group (n = 16) or a control group (n = 16). The intervention lasted 12 weeks, and adherence was assessed using validated dietary indices. Serum and follicular fluid fatty acid profiles were analyzed, and implantation and pregnancy outcomes were recorded. Results: The diet group showed increased ω-6 and ω-3 intake with decreased LA/ALA and ω-6/ω-3 ratios. In the control group, serum EPA + DHA levels declined, whereas in the diet group serum LA/ALA decreased. Follicular fluid in the intervention group had lower EPA + DHA and ω-6 ratios. Diet adherence correlated positively with MII oocytes (r = 0.797) and pronuclei (r = 0.741). No significant associations were found between follicular fluid fatty acids and IVF outcomes. A total of four implantation events were observed (intervention: n = 3; control: n = 1). Two of the implantations in the intervention group resulted in live births, while the remaining implantation events did not result in live birth. Conclusions: A Mediterranean diet-aligned dietary intervention may induce favorable changes in blood and follicular fluid parameters; however, the underlying metabolic mechanisms warrant further investigation. Three implantations were observed in the intervention group and one in the control group; given the low number of events, comparisons of live birth outcomes should be interpreted with caution. Overall, the findings regarding ART outcomes and clinical translation remain exploratory due to the limited sample size. Well-designed randomized controlled trials in which ART and clinical endpoints are defined as primary outcomes are needed. Full article

Ground-level ozone is widely acknowledged as one of the primary air pollutants, capable of inducing adverse health effects across multiple human systems, including asthma, cardiovascular events, and central nervous system dysfunction. Epidemiological and toxicological studies indicate that the onset of related systemic diseases is often attributed to ozone-mediated inflammatory responses. However, since O₃ itself lacks antigenic properties to trigger innate immune responses, an intermediary substance induced by ozone exposure likely activates subsequent inflammatory pathways. Multiple ozone exposure studies have identified mitochondrial DNA (mtDNA) as a potential biomarker released during ozone-induced mitochondrial dysfunction. mtDNA may serve as a damage-related molecular pattern that activates innate immune responses, potentially acting as a crucial link between ozone and inflammatory reactions. This review therefore examines the structure and function of mitochondrial DNA, along with potential mediating mechanisms underlying inflammation associated with ozone exposure. Full article

In recent years, imaginative techniques have effectively addressed the growing demand for brief, evidence-based treatments applicable in various contexts. Among these, Imagery with Rescripting (ImRs) was developed within the Schema Therapy model. ImRs can be applied individually or in combination with other protocols, demonstrating significant outcomes even after just one session. This narrative review aims to provide an overview of the applications of ImRs, with a specific focus on its effectiveness in trauma-related disorders. The search string used was “(‘imagery with Rescripting’) AND ((‘Trauma’ OR ‘PTSD’ OR ‘dissociation’))”. The following databases were utilized: PubMed, Scopus, Web of Science, Medline, Embase, and PsychInfo. The research included English-language and Italian-language studies, encompassing experimental and observational designs, case reports, and case series. Samples consisted of healthy participants or clinical populations aged 18 years and older, with no temporal limitations. A total of 56 articles were selected. The results highlight the efficacy of this intervention, whether administered individually or as part of combined protocols, across a wide range of diagnostic categories, including healthy samples, post-traumatic stress disorder (PTSD), borderline personality disorder (BDP), sleep disorders, psychotic spectrum disorders, chronic pain, anxiety disorders, depression, and eating disorders. The studies also support hypotheses about the mechanisms underlying the technique: ImRs facilitates the reprocessing of the meaning associated with mental representations and reduces the occurrence of negative intrusive images related to past events. This process alters and rewrites the individual’s negative memories and images. The narrative review supports the effectiveness of ImRs in treating various psychopathological disorders, both trauma-related and non-trauma-related. In addition to highlighting the effectiveness of ImRs when appropriately integrated with other techniques, the review emphasizes the importance of conducting efficacy studies on larger samples to evaluate ImRs as a standalone intervention model. Full article

Hepatitis E virus, a single-stranded positive-sense RNA virus, is the causative agent of acute viral hepatitis in humans and can lead to chronic infection in immunocompromised individuals. In this setting, strains containing host genome insertions within the polyproline region (PPR) of the pORF1 polyprotein were characterized and shown to display an increased replication rate across all systems. Using in silico modeling of pORF1 across 25 strains, combined with molecular dynamics (MD) simulations, we explored the structural variations caused by these insertions to investigate potential mechanisms underlying the increased replication rate compared to wild-type (WT) strains. Our results showed that the insertions neither induced structural organization within the PPR nor altered its intrinsically disordered nature. MD simulations further demonstrated that the overall stability of pORF1 remained unchanged in strains with insertions compared to WT strains. On the other hand, MD analyses revealed that strains with insertions exhibited an increased number of hydrogen bonds between the PPR and two other domains of pORF1: the MetY domain and the RNA-dependent RNA polymerase (RdRp). The stability of the MetY domain of the strains in the presence of host insertion events was higher than in the WT strains. These additional hydrogen bonds could position the MetY domain and the RdRp closer together, potentially promoting more efficient viral RNA synthesis. Validation of this hypothesis will require experimental structural studies, as well as computational modeling of the proposed dodecameric pORF1 structure. Full article

The skin, the largest organ in the human body, serves as a crucial barrier against external stimuli. With the acceleration of social industrialization and the worsening of global climate change, the risk of physical, chemical and biological damage to the skin has significantly increased. Among these, surgical wounds, accidental injuries, diabetic wounds, and ultraviolet (UV)-radiation-induced photoaging are particularly common. Cutaneous wound healing is a complex and dynamic process that requires precise coordination of numerous molecular events to effectively repair damaged skin. Skin photoaging, a phenomenon of premature aging caused by long-term UV exposure, is characterized by pigmentary abnormalities, telangiectasia, epidermal roughness, wrinkle formation, and precancerous lesions, all of which seriously affect skin health and appearance. Extracellular vesicles (EVs), a class of nano-sized vesicles secreted by various cells, play important regulatory roles in tissue regeneration. Although cell-culture-medium-derived EVs (C-EVs) have been proven to effectively promote skin wound healing and photodamage repair, their origin from a single cell type and challenges in large-scale production severely limit their broad application. In contrast, EVs derived from natural biological resources, including tissue-derived EVs (Ti-EVs) and plant-derived EVs (PDEVs), have emerged as novel therapeutic strategies for skin wounds and photoaging. These EVs better reflect the physiological microenvironment and demonstrate considerably higher production efficiencies. Ti-EVs, obtained from mammalian tissues composed of multiple cell types and extracellular matrix, contain more abundant regulatory factors, thus exhibiting superior bioactivity compared with C-EVs. PDEVs have also garnered significant attention due to their favorable stability, low immunogenicity, unique natural antioxidant components, and feasibility of large-scale extraction. This review will systematically elaborate on the characteristics and isolation methods of both Ti-EVs and PDEVs, as well as their therapeutic roles and underlying mechanism in wound healing and skin photoaging. Full article

Although ductal carcinoma in situ (DCIS) diagnoses continue to climb, patient management remains constrained by limitations in recurrence prediction. Conventional histopathology and existing prognostic parameters often inadequately predict local recurrence, leading to over- or under-treatment. Additionally, discourse remains over the clinical implications of margin width as a measure of recurrence risk, demonstrating the limitations of a margin-based model, and motivating our proposal that recurrence risk is dynamic and should be defined by patient-specific, spatially resolved diagnostic biomarkers. This review introduces field cancerization as a framework that may illuminate mechanisms underlying DCIS ipsilateral recurrence and improve clinical decision-making. We propose that the potential drivers of ductal field cancerization span two stages: pre-tumorigenesis and post-tumorigenesis. Pre-tumorigenic events include non-biological and biological exposome factors. Post-tumorigenic drivers include intratumoral and microenvironment-mediated remodeling of adjacent tissues that promote malignancy. This review bridges stage-specific molecular mechanisms to potentially actionable strategies for DCIS patient management—particularly margin assessment and recurrence risk prognostication—while highlighting the critical unmet need to identify biomarkers that measure high-risk field changes. We also emphasize the need to move beyond lesion-centric management toward multivariable prognostic models that include distance-mapped field biomarkers, enabling more precise surgery, improved selection of adjuvant therapy, and safer de-escalation for low-risk patients. Full article

Egypt generally experiences a hot and arid climate, with rainfall primarily confined to the northern coast during winter season. However, on 31 May 2025, Alexandria experienced an unusual late-spring convective storm that was associated with heavy rainfall, strong winds, intense lightning, and localized hail. This rare event caused temporary disruptions to urban life and underscored the growing vulnerability of coastal cities to short-duration, high-intensity precipitation events occurring outside the climatological rainy season. This study investigates the atmospheric mechanisms underlying this event through a comprehensive synoptic and dynamic analysis of pressure systems, wind fields, and temperature structures extending from the surface to the 200 hPa level. Particular emphasis is placed on the role of moisture convergence and upper-level dynamical forcing in triggering the rapid development of deep convection. Furthermore, the influence of anomalous large-scale circulation patterns on storm initiation and intensification is systematically examined. Improved understanding of these processes provides valuable insight into off-season convective activity over the southeastern Mediterranean and enhances forecasting capability, risk assessment, and early warning strategies for similar extreme events in the region. Furthermore, the influence of anomalous large-scale circulation patterns on storm initiation and intensification is quantitatively assessed to clarify their contribution to the event’s development. A deeper understanding of these processes offers critical insight into the mechanisms governing off-season convective activity over the southeastern Mediterranean and strengthens forecasting skill, risk assessment frameworks, and early warning systems for comparable extreme events in the region. Full article

West Nile virus (WNV) is a mosquito-borne flavivirus that remains an important public and veterinary health concern across Europe. Periodic outbreaks affecting humans, horses, and wildlife highlight the complex ecological interactions underlying viral circulation. This narrative review aims to synthesize current knowledge regarding WNV epidemiology, transmission dynamics, and surveillance strategies in Europe, with particular attention to the Romanian context. Available surveillance data indicate recurrent seasonal transmission in several European regions; however, reported case numbers may be influenced by differences in diagnostic capacity, reporting practices, and surveillance intensity among countries. Recent studies suggest that environmental variability, vector adaptation, and host community composition play important roles in shaping regional transmission risk, although the relative contribution of these factors remains incompletely quantified. Despite expanding surveillance networks and One Health initiatives, important knowledge gaps persist regarding the integration of environmental risk indicators, vector ecology, and operational preparedness into coherent risk-assessment frameworks. This review therefore examines current epidemiological patterns, evaluates surveillance approaches, and discusses emerging drivers of WNV transmission in Europe. As a narrative synthesis based on published literature and surveillance reports, this review is subject to limitations related to heterogeneity in available data and differences in national reporting systems. Nevertheless, a clearer understanding of these interacting factors may support improved surveillance strategies and more adaptive public health responses to future WNV transmission events. Reported surveillance data should be interpreted cautiously, as differences in national surveillance intensity, diagnostic capacity, and reporting frameworks across Europe may influence notified case numbers. Consequently, reported outbreaks do not necessarily reflect proportional differences in transmission intensity. Full article

The TIFY family, known as a novel group of transcription factors unique to the plant, plays a number of roles and has been functionally characterized in numerous plant species. However, TIFY proteins remain unexplored in litchi. Here, we identified 14 TIFY genes in litchi, which were unevenly located on 8 of 15 chromosomes. All of the LcTIFY proteins were predicted to be nuclear-localized and were phylogenetically categorized into four subfamilies (TIFY, PPD, ZML, and JAZ). Duplication analysis detected no tandem duplications but identified one segmental duplication event with LcTIFY genes, suggesting that segmental duplication served as the primary driving force for the expansion of LcTIFY genes. Comparative collinear analysis revealed 12, 5, and 27 collinear gene pairs between litchi and Arabidopsis, rice, and apple, respectively, providing valuable clues for understanding the evolution of the LcTIFY genes. RNA-Seq and qRT-PCR analyses indicated tissue-preferential expression patterns among LcTIFY genes. Notably, LcPPD1 and LcJAZ5 expressions were negatively correlated with anthocyanin accumulation in the ‘Feizixiao’ variety, except that LcJAZ5 displayed a positive correlation under CPPU treatment. In contrast, LcJAZ7 expression showed a positive correlation across all treatments, implicating these genes in the regulation of pericarp pigmentation. Collectively, these findings lay the groundwork for future investigations into the functional roles of TIFY genes in litchi and offer valuable genetic resources for elucidating the mechanisms underlying litchi pigmentation, thereby providing fresh perspectives for subsequent research into the molecular mechanisms of color formation in plants. Full article

Background/Objectives: Chronic low-grade inflammation underlies persistent pain, sleep disturbance, fatigue, and reduced perceived well-being. ACT (anti-inflammatory cellular treatment), CO (circulatory optimization), and MO (metabolic optimization) are non-invasive REAC-based biomodulation protocols within the Inside Blue Zone (IBZ) framework, yet real-world evidence on patient-reported outcomes remains limited. The aim of this study was to evaluate pain intensity and symptom burden (sleep disturbance, fatigue, perceived well-being) in subjects undergoing ACT, CO, and MO within a Post-Market Clinical Follow-Up (PMCF) framework. Methods: This prospective observational PMCF study enrolled 50 subjects receiving sequential ACT, CO, and MO in routine practice. Pain was assessed at baseline (T0), end of treatment (T1), and follow-up (T2) using a Visual Analog Scale (VAS). Secondary outcomes were analyzed through clinically meaningful severity categories. Results: VAS scores decreased significantly from T0 to T1 (t(49) = 21.37, p < 0.001, Cohen’s d = 3.02) and remained reduced at T2. Seventy-eight percent met responder criteria. Secondary outcomes shifted toward lower severity categories at both timepoints. No adverse events occurred. Conclusions: Sequential ACT, CO, and MO produced clinically meaningful pain reductions and favorable symptom severity shifts with good tolerability, supporting clinical performance of this REAC-based approach in chronic low-grade inflammatory conditions. Full article

Penile squamous cell carcinoma (PSCC) is rare, but a biologically aggressive malignancy. Recent comprehensive genomic profiling (CPG) efforts revealed the underlying genomic landscape of PSCC, identifying TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and FAT1 as frequently altered genes with potential roles in penile oncogenesis. In addition, recurrent mutations encoded in the GPS1 gene have been observed in 7.4% of cases in a particular PSCC cohort. Functional studies demonstrated loss of function due to GPS1 Exon 9 missense mutations, proposing a possible role for these alterations as oncogenic driver events in PSCC. However, no other study confirmed the occurrence of GPS1 gene mutations in PSCC. To elucidate the biological function of GPS1 exon 9 mutations in PSCC pathogenesis, we utilized a comprehensive in-house cohort of 106 PSCC cases to explore their frequency and occurrence. Albeit, the previously reported GPS1 mutations p.D382H and p.M384I were not observed in this large cohort of PSCC cases; this analysis, however, revealed two novel GPS1 alterations in exon 9 in two (1.9%) of the analyzed cases: p.S372F (c.1115C>T) and p.A375D (c.1124C>A). This observation suggests that GPS1 exon 9 sequence is a target of genetic alteration during PSCC pathogenesis. However, the non-recurrent nature of these alterations indicates that they are unlikely to represent oncogenic drivers in this disease. Full article

Membrane fusion is fundamental to intracellular transport and signal transduction, with its dysregulation implicated in various diseases. Deciphering its transient, microscale dynamics requires advanced sensing technologies. This review systematically evaluates optical and electrochemical sensing platforms for in vitro studies of membrane fusion. Optical sensing platforms provide greater intuitive readout of membrane fusion events, whereas electrochemical sensing platforms enable label-free, single-event resolution. We revisit classical fluorescence resonance energy transfer (FRET) strategies for lipid and content mixing, tracing their evolution from ensemble measurements to real-time, multiparameter, single-vesicle analysis. We further examine electrochemical platforms based on nanodisc-black lipid membranes (ND-BLMs) and solid-supported lipid bilayers (SLBs), highlighting their unique capabilities in characterizing fusion pore kinetics and virus–host membrane fusion. ND-BLM-based systems are irreplaceable for probing fusion pore kinetics, owing to their sub-millisecond temporal resolution and being essentially free from ion saturation and depletion effects. Meanwhile, SLB-based electrochemical sensing platforms excel at high-throughput detection of viral membrane fusion events by virtue of their excellent compatibility and facile integration. These sensors provide powerful tools for elucidating the molecular mechanisms underlying SNARE-mediated membrane fusion and viral fusion processes. Finally, this review outlines future directions centered on the integration of multimodal sensing and the construction of physiomimetic membranes, emphasizing the critical role of cross-scale, multiparameter sensing in bridging molecular mechanisms with biological functions and advancing the diagnosis and treatment of membrane fusion-related diseases. Full article

In the Neonatal Intensive Care Unit (NICU), clinicians must balance the demands of constant patient monitoring with the need for precise documentation and clear communication with colleagues and families. To address the clinical burden of documenting patient care and health status, this paper presents two complementary AI-based systems. First, a GAN-driven NICU Patient Simulator is developed to generate realistic neonatal vital sign data and discrete clinical intervention events, typical of care in the NICU. While useful for a variety of research goals, this simulator provides a safe and controllable data source essential for the development and validation of the second system: the LLM-powered Neonatal Patient Status Summarizer (NPSS). The NPSS fuses the output of multiple machine learning systems, each extracting specific aspects of patient care and health, together with vital sign data from a patient monitor. Leveraging Retrieval-Augmented Generation (RAG) to incorporate neonatal-specific reference data, the NPSS enables several key use cases, including generating parent-friendly updates, summarizing patient status for clinician handovers, and automatically populating patient records for charting. Simulator validation demonstrates the high fidelity of the simulated data relative to available infant data in Physionet. The NPSS is evaluated using an automated LLM-as-judge framework across repeated test scenarios. To mitigate self-preference bias, evaluations were conducted using three distinct LLM judges (OpenAI o3-mini, Llama-3, and Mistral). Across judges, the NPSS achieved consistently high relevance scores (0.95–0.99) and strong groundedness scores (0.80–0.91), indicating that generated summaries remain on-topic and faithful to the underlying simulator data. Once validated, the NPSS will reduce charting workload, improve shift handover efficiency, and streamline parental updates, addressing key clinical bottlenecks in NICU data workflows. Full article