Search Results (7,912)

Pulmonary arterial hypertension (PAH) is a rare condition characterized by high pulmonary artery pressure leading to right ventricular dysfunction and potential life-threatening consequences. It primarily affects the pre-capillary pulmonary vascular system. The exact pathophysiological mechanisms underlying PAH are not entirely known. Environmental factors; genetic predisposition; mitochondrial and microRNA dysfunction; and inflammatory, metabolic, and hormonal mechanisms may be involved. A central role is played by the dysfunction of the pulmonary vascular endothelium. This alteration is characterized by a reduction in vasodilatory and antiproliferative factors such as prostacyclin and nitric oxide and an increase in vasoconstrictive and mitogenic substances such as endothelin and thromboxane A2. Such imbalance leads to a progressive increase in pulmonary vascular resistance. The aim of the present review is to focus on the vascular endothelium and its role as a potential therapeutic target in PAH. Full article

The use of additive manufacturing (AM) has seen increased utilization over the last decade, thanks to well-documented advantages such as lower startup costs, reduced wastage, and the ability to rapidly prototype. The poor surface finish of unprocessed AM components is one of the major drawbacks of this technology, with the research literature suggesting a measurable impact on flow characteristics and burner operability. For instance, surface roughness has been shown to potentially increase resistance to boundary layer flashback—an area of high concern, particularly when utilizing fuels with high hydrogen content. A more detailed understanding of the underlying thermophysical mechanisms is, therefore, required. Computational fluid dynamics can help elucidate the impact of these roughness effects by enabling detailed data interrogation in locations not easily accessible experimentally. In this study, roughness effects on a generic gas turbine swirler were numerically modeled using a low-y+ detached eddy simulation (DES) approach. Three DES models were investigated utilizing a smooth reference case and two rough cases, the latter employing a literature-based and novel equivalent sand-grain roughness (k_s) correlation developed for this work. Existing experimental isothermal and CH₄ data were used to validate the numerical simulations. Detailed investigations into the effects of roughness on flow characteristics, such as swirl number and recirculation zone position, were subsequently performed. The results show that literature-based k_s correlations are unsuitable for the current application. The novel correlation yields more promising outcomes, though its effectiveness depends on the chosen turbulence model. Moreover, it was demonstrated that, for identical k_s values, while trends remained consistent, the extent to which they manifested differed under reacting and isothermal conditions. Full article

Background: The reported incidence of pertussis, a vaccine-preventable disease, has been increasing in recent years. This study aimed to estimate the burden of pertussis and the vaccination rate in Australian adults in primary care. Methods: Deidentified data for participants aged ≥18 years were extracted from the MedicalDirector (MD) primary care software from 2008 to 2019. We estimated the cumulative incidence of diagnosed pertussis in adults by age and risk groups and vaccine coverage in cases and a control group (not diagnosed with pertussis or a coughing illness). We also examined the incidence of unspecified coughing illness in the study population. Results: Of the 764,864 subjects included in the study, 1788 (0.2%) were diagnosed with pertussis between 2008 and 2019, corresponding to an average annual diagnosis rate of 76.9 per 100,000 population. About 31,110 (4.1%) of adults had an unspecified coughing illness. The highest rate was observed in 2011 and higher in females (63.3%), and the diagnosis rate was stable across all age groups. Underlying chronic conditions were more prevalent among pertussis cases than controls (58.7% vs. 18.8%), with asthma or chronic obstructive pulmonary disease (COPD) being the most common. Overall, 14% of cases received a pertussis vaccination during the study period. Diagnostic testing for pertussis was performed in 34.1% of pertussis cases. Estimated conservative costs per pertussis patient ranged from AUD 473 to AUD 909, with higher costs observed in individuals with complications. Conclusions: In the outpatient setting, there was a notable burden of pertussis among adults under 65 years of age, particularly those with underlying medical conditions, such as asthma and COPD, which appear to be significant risk factors. Due to the low rate of pertussis testing among all coughing illnesses, a proportion of non-specific coughing illness may be undiagnosed pertussis. The observed low vaccination rates highlight a need for increased awareness, improved diagnostic efforts, and prevention strategies in primary care. Full article

This study investigates the surface characteristics and corrosion behavior of a high-C martensitic stainless steel (AISI 440C) at different stages of its manufacturing process. As a class, these steels prioritize high mechanical properties and wear resistance over superior corrosion resistance. Hot working operations, such as rolling, create a surface oxide scale that must be removed via pickling to restore the material’s inherent corrosion resistance. This process also eliminates the underlying Cr-depleted layer, allowing for the re-establishment of a protective passive film. Using potentiodynamic polarization curves and micrographic analysis, the material’s behavior in different conditions, as-rolled, with a post-heat treatment oxide scale, and in a bare, oxide-free state, has been assessed. The results showed that the material lacks stable passive behavior under all conditions. The as-rolled and heat-treated conditions both exhibited active behavior and formed thick, non-adherent corrosion products. The oxide layer formed after heat treatment performed the worst, showing a significant increase in corrosion current density. These findings confirm the material’s susceptibility to corrosion in Cl⁻ ion-rich environments, highlighting the need for limited storage in such conditions and rapid pickling after thermal processing to mitigate surface damage. Full article

Neurodevelopmental disorders (NDDs), including autism spectrum disorder, intellectual disability, and attention-deficit/hyperactivity disorder, are genetically and phenotypically heterogeneous conditions affecting millions worldwide. High-throughput omics technologies—transcriptomics, proteomics, metabolomics, and epigenomics—offer a unique opportunity to link genetic variation to molecular and cellular mechanisms underlying these disorders. However, the high dimensionality, sparsity, batch effects, and complex covariance structures of omics data present significant statistical challenges, requiring robust normalization, batch correction, imputation, dimensionality reduction, and multivariate modeling approaches. This review provides a comprehensive overview of statistical frameworks for analyzing high-dimensional omics datasets in NDDs, including univariate and multivariate models, penalized regression, sparse canonical correlation analysis, partial least squares, and integrative multi-omics methods such as DIABLO, similarity network fusion, and MOFA. We illustrate how these approaches have revealed convergent molecular signatures—synaptic, mitochondrial, and immune dysregulation—across transcriptomic, proteomic, and metabolomic layers in human cohorts and experimental models. Finally, we discuss emerging strategies, including single-cell and spatially resolved omics, machine learning-driven integration, and longitudinal multi-modal analyses, highlighting their potential to translate complex molecular patterns into mechanistic insights, biomarkers, and therapeutic targets. Integrative multi-omics analyses, grounded in rigorous statistical methodology, are poised to advance mechanistic understanding and precision medicine in NDDs. Full article

The success and impact of biological invasions depend on adaptations to novel abiotic and biotic selective pressures. However, the genetic mechanisms underlying adaptations in invasive species are inadequately understood. Taenioides sp. is an invasive worm goby, originally endemic to brackish waters in the estuaries of Southeastern China, and now colonizes multiple inland freshwaters of North China within decades as a byproduct of the East Route of South-to-North Water Transfer (ESNT) project. However, the molecular mechanisms underlying their adaptations to the climate of North China, especially the temperature regime, are unknown. Here, we performed genomic resequencing analysis to assess genetic diversity and population genetic structure, and further investigated the genomic signatures of local adaptation in the invasive population of Taenioides sp. during their northward invasion. We revealed that all invasive populations exhibited no genetic differentiation but low gene flow and an obvious signal of population bottleneck. Yangtze River estuary may serve as the source population, while Gaoyou Lake serves as a potential bridgehead of the invasion. Selective sweep analyses revealed 117 genomic regions, containing 673 candidate genes, under positive selection in populations at the invasive front. Redundancy analysis suggested that local temperature variables, particularly the monthly minimum temperature, represent critical evolutionary forces in driving adaptive divergence. Functional enrichment analyses revealed that multiple biological processes, including metabolism and energy production, substance transmembrane transport, and neural development and synaptic transmission, may play important roles in adaptation to regional temperature conditions. Our findings revealed a scenario of adaptive evolution in teleost species that underpins their regional climate adaptation and successful establishment of invasive populations in a human-facilitated invasion context. Proper management strategies should be established to manage Taenioides sp invasion as soon as possible. Full article

Background: Post-traumatic joint contracture (PTJC) remains one of the most prevalent and challenging complications arising from musculoskeletal trauma or surgical intervention. Conventional treatment modalities are largely reactive and address symptoms after onset, yet provide limited efficacy once contracture has developed. In contrast, pharmacological strategies targeting the underlying inflammatory and fibrotic pathways offer a promising strategy for preventing the development of PTJC altogether. Methods: A total of 26 male Sprague Dawley rats underwent standardized knee trauma followed by immobilization for a duration of two weeks. Rats were randomized into two groups. The experimental group (n = 13) received bosentan at a dosage of 50 mg/kg twice daily throughout the immobilization period. The control group (n = 13) received a placebo instead. Joint mobility was quantitatively assessed by measuring the contracture angle (CA) and resistance to extension. In addition, posterior joint capsule tissues were harvested for histological analysis and subjected to quantitative PCR (qPCR) to quantify the expression of profibrotic genes, including α-Sma, Il-6, Tgf-β1, Nfκ-b, Ctgf. Results: Bosentan had no relevant effect on the biomechanics of the contracture compared to the placebo group. The contracture angle was comparable between the groups (86.8° ± 14.1°, 84.8° ± 11.1°). Similarly, the force required to achieve knee joint extension was comparable between the groups. Gene expression analysis also provided no evidence of reduced expression of pro-inflammatory or profibrotic genes. Histological assessments revealed no change in the absolute or relative number of myofibroblasts, or in the number of vessels, in the posterior joint capsules of the rats treated with bosentan. Compared to the control group, the number of myofibroblasts significantly increased in both the bosentan and control groups (p < 0.001, one-way ANOVA). Conclusion: Bosentan’s purported antifibrotic properties do not appear to confer a preventative effect on the development of PTJC. These findings suggest that, despite its potential in modulating fibrosis, bosentan does not mitigate the progression of the fibrotic condition. Furthermore, the involvement of endothelin-1 (ET-1) in the pathophysiology of PTJC remains yet to be fully understood, warranting further investigation. Full article

Introduction: Canine sinonasal aspergillosis (SNA) can present singular as a primary disease or secondary to concurrent sinonasal pathology. We hypothesized that treatment response and prognosis differ between both forms, particularly when sinusitis is present. Methods: In this retrospective study, 30 dogs with SNA were categorized as either group pA (primary aspergillosis) or group sA (secondary aspergillosis; with additional sinonasal pathology). History, diagnostics, endoscopic therapeutic intervention of affected nose and sinus, and follow-up data were analyzed. Results: Group pA included 19/30 dogs (63%), with 15 dogs (79%) showing concurrent sinusitis. Group sA included 11/30 dogs (37%; additional conditions: foreign bodies, dental pathologies, frontal bone fracture). Only 2/11 sA dogs (18%) had sinusitis. Follow-ups in group pA were more frequent than in group sA (p = 0.04). Need for re-treatments differed significantly between groups (p = 0.02) and in dogs with sinusitis, regardless of group (p < 0.001). In group sA, treating the underlying condition plus single endoscopic debridement ± antifungal therapy led to clinical resolution in 11 of 12 dogs (92%). Conclusions: Primary SNA is frequently associated with sinusitis, requires aggressive repeated antifungal therapy, and may not achieve a definitive cure. Secondary SNA is usually confined to the nasal cavity, responds well to underlying condition treatment, carries better prognosis, and requires fewer antifungal treatments. Full article

Background: C3 glomerulopathies (C3G), including dense deposit disease (DDD) and C3 glomerulonephritis (C3GN), are rare kidney disorders driven by dysregulation of the alternative complement pathway. Eculizumab, a terminal complement inhibitor targeting C5, has emerged as a potential therapeutic option in these conditions. This systematic review evaluated the efficacy and safety of eculizumab in patients with C3G or DDD. Methods: Literature searches in PubMed and Cochrane databases identified case reports and case series reporting eculizumab use. Results: Only eight studies involving ten patients met the inclusion criteria. Eculizumab stabilized renal function and reduced proteinuria in most cases, especially when C5b-9 deposition was present. Histopathological improvements were variable, and recurrence after discontinuation occurred in some patients. Responses were limited in cases with alternative mechanisms of C5 activation. Conclusions: Eculizumab offers clinical benefit in select C3G and DDD patients but does not address the underlying cause of complement dysregulation. The need for long-term therapy, incomplete histologic resolution, and risk of relapse underscore the necessity of larger trials and the development of personalized treatment strategies. Full article

Psoriasis is a chronic, immune-mediated dermatosis that affects approximately 125 million people worldwide. Traditionally considered a dermatologic condition, it is now perceived as a systemic disease with numerous comorbidities. While its associations with psoriatic arthritis, metabolic syndrome, and psychiatric disorders are well established, less attention has been given to its coexistence with other dermatoses. This narrative review aims to explore and summarize the existing evidence on the relationships between psoriasis and other skin diseases, highlighting potential overlaps in clinical presentation, pathogenesis, and treatment challenges. Psoriasis may coexist with several inflammatory and autoimmune skin disorders, including atopic dermatitis, lichen simplex chronicus, anti-p200 pemphigoid, pityriasis rubra pilaris, seborrheic dermatitis, inflammatory linear verrucous nevus (ILVEN), Sneddon–Wilkinson disease, and vitiligo. The review highlights the shared genetic pathways (e.g., the Th1/Th17 axis and IL-17 pathway), diagnostic challenges (e.g., sebopsoriasis and psoriasis–eczema overlap), and therapeutic considerations (e.g., paradoxical reactions to biologics and effectiveness of JAK inhibitors in both psoriasis and vitiligo). The coexistence of psoriasis with other dermatoses is more common and clinically significant than previously appreciated. Recognizing these associations is crucial for an accurate diagnosis, avoiding mismanagement, and optimizing individualized treatment strategies. Further research is needed to elucidate the underlying mechanisms and improve the multidisciplinary care for patients with complex dermatologic presentations. Full article

With the widespread integration of Artificial Intelligence-Generated Content (AIGC) into e-commerce platforms, understanding how users perceive, evaluate, and respond to such content has become a critical issue for both academia and industry. This study examines the influence mechanism of AIGC Content Quality (AIGCQ) on users’ Purchase Intention (PI) by constructing a cognitive model centered on Trust (TR) and Perceived Risk (PR). Additionally, it introduces two moderating variables—Ethical Concern (EC) and Perceived Platform Responsibility (PLR)—to explore higher-order psychological influences. The research variables were identified through a systematic literature review and expert interviews, followed by structural equation modeling based on data collected from 507 e-commerce users. The results indicate that AIGCQ significantly reduces users’ PR and enhances TR, while PR negatively and TR positively influence PI, validating the fundamental dual-pathway structure. However, the moderating effects reveal unexpected complexities: PLR simultaneously amplifies both the negative effect of PR and the positive effect of TR on PI, presenting a “dual amplification” pattern; meanwhile, EC weakens the strength of both pathways, manifesting a “dual attenuation” effect. These findings highlight the nonlinear cognitive mechanisms underlying users’ acceptance of AIGC, suggesting that PLR and EC influence decision-making in more intricate ways than previously anticipated. By uncovering the unanticipated patterns in moderation, this study extends the boundary conditions of the trust–risk theoretical framework within AIGC contexts. In practical terms, it reveals that PLR acts as a “double-edged sword,” providing more nuanced guidance for platform governance of AI-generated content, including responsibility frameworks and ethical labeling strategies. Full article

The Qiongdongnan Basin constitutes a sedimentary basin characterized by elevated temperatures, significant overpressures, and abundant hydrocarbons. Investigations within this basin have identified hydrothermal fluid movements linked to overpressure conditions, comprising two vertically separated overpressured intervals. The shallow overpressure compartment is principally caused by a combination of undercompaction and clay diagenesis. In contrast, the deeper high-pressure compartment results from hydrocarbon gas generation. Numerical pressure modeling indicates late-stage (post-5 Ma) development of significant overpressure within the deep compartment. It is proposed that accelerated subsidence in the Pliocene-Quaternary initiated substantial gas generation, thereby promoting the formation of the deep overpressured system. Multiple organic maturation parameters, combined with fluid inclusion microthermometry, reveal a thermal anomaly adjacent to the upper boundary of the deep overpressured zone. This anomaly indicates vertical transport of hydrothermal fluids ascending from the underlying high-pressure zone. Laser Raman spectroscopy confirms the presence of both hydrocarbons and carbon dioxide within these migrating fluids. Integration of fluid inclusion thermometry with burial history modeling constrains the timing of hydrocarbon-carrying fluid charge to the interval from 4.2 Ma onward, synchronous with modeled peak gas generation and a phase of pronounced overpressure buildup. We propose that upon exceeding the fracture gradient threshold, fluid pressure triggered upward migration of deeply sourced, hydrocarbon-enriched fluids through hydrofracturing pathways. This process led to localized dissolution and fracturing near the top of the deep overpressured system, while simultaneously facilitating significant hydrocarbon accumulation and forming preferential accumulation zones. These findings provide critical insights into petroleum exploration in overpressured sedimentary basins. Full article

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social communication and repetitive behaviors, involving various brain regions. Emerging evidence highlights the critical role of the cerebellum in the pathophysiology of autism; however, the underlying molecular mechanisms remain poorly understood. This study aimed to establish a prenatal valproic acid (VPA)-induced mouse model of ASD and explore the potential molecular mechanisms underlying cerebellar ASD-like phenotypes through DIA-based proteomics and bioinformatics analyses. Significant cognitive impairment and anxiety-like behaviors were detected using an open field test and novel object test following VPA exposure, respectively. Additionally, reduced numbers of Purkinje cells with irregular arrangement were observed in the cerebellum. Furthermore, cerebellar proteomics analyses revealed that they identified 193 differentially expressed proteins (DEPs) involved in multiple pathways, including axon guidance, glutamatergic synapse, long-term potentiation, and calcium signaling, among others. Notably, dysfunction of glutamate receptor signaling and disruptions in axon-guidance signaling appear to be major molecular mechanisms underlying cerebellar impairment. Together, these findings suggest that Grin2b may serve as a critical molecule linking synaptic neurotransmission and neurodevelopmental disorders. Thus, Grin2b may represent a potential therapeutic target for addressing cognitive impairment in ASD. Full article

Background: Parathyromatosis, an exceptional clinical and pathological entity, involves multiple small nodules of hyper-functional parathyroid tissue scattered throughout the neck and/or mediastinum, in relationship with a prior parathyroidectomy (mostly) or embryologic remnant. Since its first identification in 1975, many aspects of this condition have remained a matter of debate. Objective: We introduce an updated perspective on parathyromatosis covering the main clinical points for everyday practice, from diagnosis to management, as well as the current level of pathogenic understanding. Methods: A narrative review. Results: A total of 22 patients were identified, with the following characteristics: an age range of 33–68 (mean 46.18) years; 4/22 subjects <40 years; female-to-male ratio = 14:8. Of the 22 subjects, 21 had undergone previous parathyroidectomy for primary (n = 14) or secondary (n = 7) hyperparathyroidism. One case was a surgically naïve patient. Analysis of the surgical procedures (seeding circumstances) revealed the following: parathyroid cyst removal, left/right parathyroidectomy; removal of 3.5 parathyroids ± self-transplantation, VATS for mediastinal parathyroid tumours. Parathyroidectomy was accompanied by thyroid surgery (n = 3 patients), specifically hemi-thyroidectomy, partial left-thyroid lobectomy, and partial thyroidectomy. The shortest timeframe from parathyroidectomy to parathyromatosis-related hyperparathyroidism recognition was 1 year, and the longest was 17 years. The highest number of previous surgeries was four. The recognition of parathyromatosis was due to the clinical picture of associated hyperparathyroidism, except for in 2/21 cases with incidental detection. The implant sites coincided with the prior surgical area, but also with unusual locations (clavicle, pleura, mediastinum, sternocleidomastoid muscle and forearm, thyroid). The imaging evaluation included ultrasound plus CT plus 99m-Tc sestamibi scintigraphy, as well as (variable rates) neck MRI, SPECT/CT, 11-Choline PET-CT, Gallium-68 DOTATATE, and 4D CT. Surgery implied serial procedures in some cases (e.g., up to seven). The surgery spectrum largely varied, including not only cervicotomy, but also thoracoscopy, VATS, pericardial adipose tissue excision and thymectomy, etc. Conclusions: Awareness remains a key factor when approaching such an unusual ailment underlying little-understood pathogenic loops, which, if left unrecognized and untreated, might impair patients’ quality of life and the overall parathyroid disease burden. Full article

Functional bowel disorders (FBDs) are chronic gastrointestinal conditions characterized by recurrent symptoms associated with gut microbiota dysbiosis. Although accumulating evidence suggests that probiotics can improve symptoms in patients with FBD, the underlying mechanisms remain to be fully elucidated. In this randomized, double-blind, placebo-controlled clinical trial, 38 adults meeting the Rome IV diagnostic criteria of functional constipation (FC) and functional diarrhea (FD) received either a multi-strain probiotic complex or placebo for 8 weeks. Clinical outcomes were evaluated using the Irritable Bowel Syndrome Severity Scoring System (IBS-SSS), bowel habits questionnaire, and IBS Quality of Life (IBS-QoL) instrument. Fecal samples were collected at baseline and at week 8 for gut microbiota profiling via 16S rRNA gene sequencing and metabolomic analysis using gas chromatography–mass spectrometry. Probiotic supplementation significantly reduced the severity of abdominal bloating and its interference with quality of life, and improved the body image domain of the IBS-QoL. Beta diversity analysis showed significant temporal shifts in the probiotic group, while 16S rRNA sequencing revealed an increased relative abundance of Faecalibacterium prausnitzii and Blautia stercoris. Fecal metabolomic analysis further indicated elevated levels of metabolites implicated in the gut–brain axis. Multi-strain probiotic supplementation alleviated gastrointestinal symptoms and improved aspects of psychosocial well-being in adults with FBDs, potentially through modulation of the human gut microbiome. Full article