Triple-negative breast cancer (TNBC) lacks targeted therapies and is driven by dysregulated signaling networks that promote migration, invasion, and survival. Connexin43 (Cx43), a gap junction protein essential for maintaining normal mammary epithelial homeostasis, becomes aberrantly phosphorylated and mislocalized in breast cancer, contributing to disease progression. Because the tyrosine kinases Pyk2 and Src regulate Cx43 and multiple pro-tumorigenic pathways, we investigated whether their combined inhibition could suppress malignant behaviors in TNBC. In MDA-MB-231 cells, the Pyk2 inhibitor PF4618433 and Src inhibitor Saracatinib modestly reduced metabolic activity at high concentrations; however dual treatment produced a dose-dependent and synergistic reduction in viability. In migration and invasion assays, each inhibitor reduced motility, however dual inhibition produced the strongest suppression. Cx43 knockdown impaired baseline migration and invasion and altered the response to Pyk2/Src inhibition, indicating that Cx43 modulates sensitivity to these agents. PF4618433 increased Cx43 plaque formation without changing total protein levels. Mechanistically, Pyk2 inhibition reduced phosphorylation of Cx43 at Y265 and decreased levels of TAZ, p-Erk1/2, p130Cas, and Notch1, whereas Src inhibition only reduced p-Erk1/2. Dual treatment did not further decrease these signaling nodes but nonetheless produced stronger functional inhibition of viability and motility, and the shared regulation of p-Erk1/2 by Pyk2 and Src may help explain how compensatory Pyk2 activation limits the effectiveness of Src-targeted therapies. Together, these findings show that coordinated Pyk2 and Src inhibition restores Cx43 organization and disrupts multiple malignant traits in TNBC cells, supporting this combination as a promising therapeutic strategy.
We aimed to clarify the differences in clinical and histological characteristics between two decompression techniques for obstructive colorectal cancer (OCRC): trans-anal decompression tube (TADT) and self-expandable metallic stent (SEMS). Overall, 96 of 175 patients with OCRC treated in our department between 2000 and 2020, were assigned into TADT (n = 44) and SEMS (n = 52) groups, and the success rate and complications of decompression, surgical outcomes, clinicopathological findings, and prognosis were compared. The technical success rate was high in all patients. During surgery, the SEMS group showed significant differences in laparoscopy (p < 0.01), D3 dissection (p < 0.001), and the number of lymph nodes dissected (p < 0.01). In multivariate analysis, lymphatic invasion was associated with decompression (odds ratio [OR], 5.49; 95% confidence interval [CI], 2.12-14.20; p < 0.01) and lymph node metastasis (OR, 4.44; 95% CI, 1.69-11.70; p < 0.01), while SEMS was associated with venous invasion (OR, 0.40; 95% CI, 0.16-0.98; p = 0.04). The 5-year and recurrence-free survival rates for 70 patients with stage II and III OCRC were 76.7% and 73.2%, respectively. Although there was no significant difference in the overall survival, the recurrence-free survival was significantly better in the SEMS group (85.0% vs. 58.3%, p = 0.04). The results of this study suggest that SEMS may be preferable to TADT from a histological perspective.
In males, prostate cancer (PCa) is one of the frequently diagnosed forms of cancer, with high clinical variability and limited treatment options for advanced cases. This receptor, which goes by the names Coagulation Factor II Receptor (F2R) and PAR1, belongs to the family of G-protein-linked membrane proteins and plays roles in both blood clotting processes and the development of malignancies. Whereas F2R has been associated with tumor progression in various malignancies, its specific involvement in PCa is not well understood. Here, we seek to examine the expression patterns and biological functions of F2R to better understand its impact on PCa progression. We systematically analyzed F2R expression in PCa using data from the TCGA database and clinical specimens. Functional experiments, including cell proliferation, invasion, and apoptosis assays, were conducted in PCa cell lines with F2R overexpression or knockdown. Bioinformatics analyses were performed to identify F2R-associated genes and signaling pathways. In vivo xenograft models were used to validate the oncogenic role of F2R. Our results demonstrated that F2R is significantly overexpressed in PCa tissues and correlates with advanced clinicopathological features such as higher T stage, nodal metastasis, and elevated Gleason scores. Functional studies revealed that F2R promotes PCa cell proliferation, invasion, and cell cycle progression while inhibiting apoptosis. Mechanistically, we identified collagen type VIII alpha 1 (COL8A1) as a key downstream effector of F2R, which activates the FAK/PI3K/AKT signaling pathway. In vivo experiments confirmed that F2R knockdown suppresses tumor growth and downregulates this signaling axis. This study highlights F2R as an important promoter in PCa progression and identifies the F2R-COL8A1-FAK/PI3K/AKT signaling axis as a potential molecular mechanism underlying tumor aggressiveness.
Primary breast angiosarcoma is an exceedingly rare malignancy with a high propensity for hematogenous metastasis, though skull base and dural involvement have never been reported. We present a 52-year-old woman diagnosed with stage IIA primary breast angiosarcoma (pT2N0M0) treated with mastectomy and adjuvant radiotherapy. Twenty-one months post-radiation therapy, she developed left orbital swelling and headache. Magnetic resonance imaging (MRI) revealed a 45×35-mm heterogeneously enhancing mass that extended from the skull base to the orbit with dural invasion, confirmed histologically as metastatic angiosarcoma. Following progression after radiotherapy and six cycles of anthracycline-based chemotherapy, salvage therapy combining anlotinib, a multi-target antiangiogenic tyrosine kinase inhibitor, and temozolomide, a blood-brain barrier-penetrant alkylating agent, was initiated. Within one week, her headache resolved, and three-month MRI demonstrated stable disease with resolution of temporalis enhancement and reduced dural thickening. The regimen was well-tolerated with no adverse events. At five-month follow-up, the patient remains progression-free. To our knowledge, this report describes the first documented case of skull base metastasis and dural involvement from primary breast angiosarcoma. The anlotinib-temozolomide combination achieved rapid symptomatic and radiographic control after multimodal therapy failure, suggesting synergistic efficacy against both angiogenesis and sanctuary-site disease. This report underscores the importance of targeting angiogenesis and leveraging central nervous system (CNS)-penetrating agents in angiosarcoma with atypical CNS dissemination, offering a novel therapeutic strategy for this aggressive malignancy.
This study documents the first confirmed case of JSRV-associated nasal adenocarcinoma in a goat through a comprehensive analysis combining histopathological, immunohistochemical, and molecular techniques.An autopsy was conducted on a 12-month-old goat exhibiting progressive nasal obstruction. Tissue samples from the nasal mass were examined histologically using H&E staining. Immunohistochemical (IHC) analysis was performed to detect JSRV capsid protein expression and to assess cellular proliferation markers (Ki-67 and PCNA). Molecular screening via PCR was carried out using primers specific for JSRV, ENTV-1, ENTV-2. The JSRV-positive PCR amplicon was sequenced and subjected to phylogenetic analysis.PCR analysis confirmed the presence of JSRV proviral DNA (385 bp) in the tumor tissue, while results for ENTV-1 and ENTV-2 were negative. Histopathological examination identified a mixed glandular adenocarcinoma arising from the surface and glandular epithelium, with evidence of turbinate bone invasion. IHC revealed multifocal positivity for JSRV capsid antigen and indicated a high proliferation index (30-35%). Phylogenetic analysis classified the detected viral strain within the exogenous JSRV group. The infected goat originated from a herd with no documented contact with sheep.This case provides the first conclusive evidence of JSRV-induced nasal adenocarcinoma in a goat, indicating a potential expansion of the virus's host and tissue tropism. These findings highlight the necessity for further investigation into the viral envelope-receptor interactions and promoter elements that govern JSRV tropism.
Hepatocellular carcinoma (HCC) shows a marked predominance in men, yet the molecular basis for this sex disparity remains unclear. The present study leveraged multi-omics data and machine learning algorithms to identify key genes associated with sex-specific differences in HCC and to screen for putative candidate compounds, aiming to provide new insights for sex-specific therapy. The mRNA expression data of male and female patients with HCC and paracancerous tissues were obtained from the GEO and TCGA databases. To mitigate overfitting, data were partitioned into independent training and testing sets. Candidate genes were screened by differential expression analysis and weighted gene co-expression network analysis. A total of four complementary algorithms, random forest, support vector machines, generalized linear models and extreme gradient boosting were used to identify key genes with high predictive capability. CYP17A1 and IRX3 were identified as the top differentially expressed core genes associated with HCC in men. Pan-cancer analysis showed that CYP17A1 was lowly expressed in the majority of tumors, but significantly highly expressed in HCC, rectal adenocarcinoma and gastric cancer (P<0.001). Functional cell-based assays showed that knockout of CYP17A1 inhibited the proliferation, migration and invasion ability of HCC cells (P<0.001). Immunohistochemistry showed that CYP17A1 protein expression was significantly increased in HCC tissues from male patients when compared with that in paracancerous tissues (P<0.001), whereas there was no significant difference in female patient tissues (P>0.05). Notably, while IRX3 was identified computationally, its functional role remains to be experimentally validated. Molecular docking predicted a potential interaction between the natural compound Saikosaponin A and the CYP17A1 protein, and cellular assays revealed that it dose-dependently inhibits HCC cell malignant phenotypes. The present study suggests that CYP17A1 is associated with sex differences in HCC, potentially via the androgen signaling axis. Furthermore, IRX3 emerges as a novel hypothesis-generating candidate gene. Finally, the findings of the present study highlight Saikosaponin A as a putative therapeutic candidate for male patients with HCC, warranting further target-dependency investigations.
Russia's aggression against Ukraine has unfolded in two phases: the onset of the Donbas war and the annexation of Crimea in 2014, and the full-scale invasion in 2022. We examined the changes in Ukrainian scholarly publishing across these disruption periods. Using Web of Science Core Collection and InCites data (1991-2024), we analyzed publication trends in Ukraine and Croatia, disciplinary composition, leading universities, city-level output in occupied territories, and international collaboration. Interrupted time series (ITS) models were specified with breakpoints at 2014 and 2022. Ukraine's output increased from 331 articles in 1991 to 12,475 in 2021, then declined by 14.6% to 10,649 in 2024, whereas Croatia's output remained comparatively stable. The segmented ITS showed significant growth before 2014, a steeper upward trend after 2014, and a decline after 2022. Croatia showed continued growth with a smaller, non-significant post-2022 slowdown. In Ukraine, the largest post-2022 declines were observed in Physical Sciences and Social Sciences, while Engineering and Technology appeared more resilient. City-level analyses in occupied territories showed an early break in 2014 in Donetsk and Luhansk, while output linked to Simferopol and Sevastopol was rapidly reclassified after 2014, with records increasingly indexed under Russia. After 2022, collaboration with Russia collapsed, whereas partnerships with Poland, Germany, and the USA expanded. Ukrainian scholarly publishing showed phase-specific shifts in output and collaboration patterns that coincided with major geopolitical disruptions.
ADAMTS2, a secreted metalloproteinase essential for collagen maturation, exhibits context-dependent roles in cancer but remains uncharacterized in prostate cancer (PCa). Its potential involvement in PCa progression and underlying mechanisms are unknown. We integrated bioinformatic analysis of TCGA-PRAD data with clinical specimen validation, in vitro functional assays (proliferation, migration, invasion), co-immunoprecipitation (Co-IP), ferroptosis sensitivity testing, pharmacological inhibition, and in vivo xenograft models to investigate ADAMTS2's expression, function, and molecular mechanisms in PCa. ADAMTS2 was significantly upregulated in PCa tissues and cell lines, correlating with aggressive clinicopathological features and poor progression-free survival. Functionally, ADAMTS2 promoted PCa cell aggressiveness in vitro and tumor growth in vivo. Mechanistically, ADAMTS2 directly interacted with and upregulated COL1A1, leading to stimulation of the FAK/PI3K/AKT pathway. This cascade, in turn, enhanced the expression of ferroptosis defense proteins (SLC7A11 and GPX4), suppressed lipid peroxidation, and conferred resistance to ferroptosis. Pharmacological inhibition of FAK reversed both the oncogenic and anti-ferroptotic effects of ADAMTS2. Our investigation considers ADAMTS2 as a novel oncogenic driver in PCa that promotes tumor progression by reinforcing a tumor-permissive extracellular matrix through upregulation of COL1A1 and by stimulating the FAK/PI3K/AKT pathway to suppress ferroptosis. These findings position ADAMTS2 as a potential predictive biomarker and a valuable therapeutic target for defeating ferroptosis resistance in PCa.
Bone defect is a prevalent and complex challenge in orthopedics and oral-maxillofacial surgery, severely compromising skeletal integrity and functional recovery. Autologous Guided Bone Regeneration (GBR) has emerged as a highly effective therapeutic strategy, demonstrating remarkable efficacy in treating long bone fractures, nonunions, post-tumor resection bone defects, and alveolar bone augmentation for dental implant procedures. This narrative review comprehensively synthesizes the latest research progress, core mechanisms, technical innovations, existing challenges, and future prospects of Autologous GBR through an extensive analysis of domestic and international literature. Its core mechanism relies on selective cell occlusion theory: barrier membranes construct a bone regeneration microenvironment, blocking non-osteoblastic invasion while promoting osteoblast migration and differentiation. Autologous components play key roles: autologous bone (gold standard for grafting) has osteogenic activity, osteoinductivity and osteoconductivity; autologous bone marrow provides mesenchymal stem cells (MSCs) for osteoblast differentiation and microenvironment regulation; autologous growth factors (e.g., Bone Morphogenetic Proteins [BMP], Transforming Growth Factor-β [TGF-β]) regulate bone regeneration via cell signaling pathways. Technical advances include site-specific autologous bone harvesting (ilium, mandible, etc.) and optimized barrier membranes (absorbable Poly Lactic-co-Glycolic Acid [PLGA]/collagen, non-absorbable expanded Polytetrafluoroethylene [ePTFE]). Cell-molecular studies (MSCs differentiation, Wnt pathway) offer theoretical basis. Challenges include surgical infection, potential immune rejection and poor osseointegration. Prospects involve 3D-printed scaffolds, gene therapy-tissue engineering combination, and application in complex diseases like osteogenesis imperfecta. This review provides references for researchers and clinicians.
Muscle-invasive bladder cancer (MIBC) is clinically heterogeneous, and current molecular subtyping does not capture the spatial organization of tumor states and microenvironmental context. Here, we construct a spatial atlas of MIBC by integrating spatial transcriptomics from 22 tumors with matched bulk RNA and whole-exome sequencing data. We identify a continuous, spatially organized luminal-to-basal axis within individual tumors that is associated with greater chromosomal instability and transcriptional plasticity. Luminal tumor cores are enriched for FGFR3 and NECTIN4, whereas basal-like states localize toward invasive margins and are associated with elevated EGFR signaling, epithelial-mesenchymal transition, genomic instability, immune infiltration, and greater chemotherapy sensitivity. Spatial analyses further reveal lineage- and location-associated differences in tertiary lymphoid structure states. Pan-cohort analyses across over 3,000 tumors confirm conserved FGFR3-EGFR lineage exclusivity and associated immune programs. Together, these findings define a spatial framework for understanding lineage states, immune architecture, and therapeutic vulnerabilities in MIBC.
Percutaneous vertebroplasty is a commonly used, minimally invasive therapeutic intervention to relieve pain caused by vertebral compression fractures, which are becoming more prevalent due to the aging population. Although the procedure is generally safe, complications such as cement leakage into the bloodstream can occur. We present the case of a 67-year-old female with a history of advanced osteoporosis and multiple vertebroplasty procedures who developed dyspnoea 5 months after her most recent surgery. Imaging revealed an intracardiac cement embolism extending from the inferior vena cava through the right atrium and tricuspid valve into the right ventricle. This rare complication of vertebroplasty, caused by cement leakage, resulted in tricuspid valve regurgitation and pulmonary hypertension. This case highlights the importance of recognizing and managing the rare complications of vertebroplasty by using a multimodality imaging approach, especially in patients with a history of multiple procedures.
Microcirculatory dysfunction is central to the pathophysiology of diseases such as sepsis, diabetes, and cardiovascular disorders. While clinical tools like near-infrared spectroscopy (NIRS) and transcutaneous oxygen monitoring (TcPO₂) offer global oxygenation insights, they lack the spatial resolution for localized microvascular assessment. Photoacoustic computed tomography provides sub-millimeter oxygenation imaging, yet resolving ultra-fine structures for morphology-based functional analysis remains challenging. To address this, we developed the Nine-Grid Segmentation Strategy (NGSS), a significance-analysis framework integrated with a non-invasive vascular occlusion test (VOT). Using the microcirculation-rich thenar muscle as the imaging site, NGSS characterizes each pixel across two physiological dimensions: occlusion response and reperfusion efficiency. The NGSS framework categorizes pixels based on their oxygenation trajectories during occlusion and reperfusion, assigning each to one of three functional states: significant increase, non-significant change, or significant decrease. This two-dimensional classification generates a nine-type map capturing the spatial heterogeneity of tissue microregions. Our results demonstrate that even without discerning specific microvascular morphologies, NGSS evaluates tissue oxygenation on a hundred-micron scale. The analysis reveals distinct oxygenation patterns and perfusion efficiencies across phenotypes, providing quantitative volumetric distributions. NGSS offers a novel, high-resolution, non-invasive approach for microcirculatory assessment, showing significant promise for both clinical monitoring and fundamental vascular research.
Current daily usage of Trastuzumab Deruxtecan (T-DXd) is guided by immunohistochemistry (IHC)-based HER2 assessment, with known inconsistency and inaccuracy to differentiating IHC 0 from 1 +. In this study, a quantitative HER2 assay based on the Quantitative Dot Blot (QDB) method was explored to fill this unmet need. Consecutive resection specimens of HER2 IHC 0 and 1+ from invasive breast cancer patients were assigned to training (n=106) and validation cohorts (n=119), respectively by admission time. Protein lysates were extracted from 2x5 μm FFPE slices for HER2 quantification while the adjacent slice was used for IHC staining. QDB was demonstrated to be more consistent than IHC with an inter-rater Intraclass Correlation Coefficient (ICC) of 0.877 (95%CI: 0.840-0.908) vs. 0.513 (95%CI: 0.433-0.601). Receiver Operating Characteristic (ROC) analysis was performed benchmarked with unanimous agreement of 18 pathologists in the training cohort to achieve an Area Under the Curve (AUC) of 0.9477 (p<0.005). A cutoff of 0.2746 nmole/g was also identified with its imprecision interval to stratify specimens into 0 (<C5), equivocal (≥ C5 & ≤ C95) and 1+ (> C95), with overall concordance of 90.9% and 87.3% when benchmarked with unanimous and consensus agreement (≥75%) of pathologists in the training cohort, and 92.0% and 90.5% when validated double-blinded with 12 pathologists in the validation cohort. More importantly, even among specimens unanimously categorized as IHC 0, there were ~15% specimens classified as 1+ by QDB. Our results supports the QDB HER2 assay as an alternative option to guide T-DXd daily usage by distinguish Her2-low from Her2 0 while setting the stage for outcome-based patient stratification.
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children. Optical Coherence Tomography (OCT) and Visual evoked potentials (VEP) are common non-invasive diagnostic techniques. Researchers can use these techniques to identify possible biomarkers and explore the neurodevelopmental mechanisms underlying ADHD. The ADHD group (37 cases, average age 8.81 ± 1.44 years) and the healthy controls (38 cases, average age 8.97 ± 1.43 years), had the OCT and VEP. The retinal nerve fibre layer (RNFL), optic disc parameters, and macular parameters were measured through OCT. The latencies of P100 and the amplitudes of N75-P100 and P100-N135 waves at three different spatial frequencies (visual angles of 15', 30', and 60') were tested through VEP. The average RNFL and RNFL in each quadrant between the two groups were no statistically significant (all p > 0.05). The optic disc area, average cup-to-disc ratio, and cup volume in the ADHD group were all significantly larger than those in the control group (all p < 0.05). At three visual angles (15', 30', 60'), P100-latency in the ADHD group were all more significant than those in the control group (all p < 0.05). The amplitudes of N75-P100 and P100-N135 in the ADHD group were all statistically significantly lower than those in the control group (all p ≤ 0.001). From the perspective of electroencephalophysiology, children with ADHD may have early visual information processing disorders. This provides a theoretical and practical basis for further early intervention in children with ADHD from the field of visual perception. The study protocol followed the tenets of the Declaration of Helsinki, was approved by the local ethics committee (No 2023-2240), and was registered on ClinicalTrials.gov (ChiCTR2400086223).
Roots play a pivotal role for plant performance, but they are difficult to access, which hampers quantitative measurements. Repeated imaging of rhizotrons, flat growth containers with a transparent side, has proven suitable to assess dynamics of root traits in indoor experiments. However, measuring hundreds of soil-grown plants with high temporal resolution remains a laborious challenge. We introduce a novel whole-plant phenotyping platform with a capacity of almost 900 rhizotrons, which we named GrowScreen-Rhizo 3. This platform was designed to image shoots and roots of individual plants simultaneously and derive digital proxy traits for biomass and growth. In addition, built-in weighing and watering stations deliver water use data for each rhizotron. To achieve the desired throughput (image all 896 plants once a day) a high degree of automatization and standardization was required. We realized a modular plant-to-sensor solution, using a fleet of automated guided vehicles (AGVs) to transport large rhizotrons (80 × 40 × 5 cm) to four measurement chambers for daily imaging, weighing, and watering. Simultaneous imaging of the root system with a high-resolution camera (116 μm per px) and the shoot from six different viewing angles allows to monitor plant growth with high spatial and temporal accuracy. First, we verified that moving plants to the measurement chambers did not significantly affect above- or belowground plant growth. Next, we measured phenotypic variation in root and shoot traits of 24 barley genotypes, parents of a nested association mapping population. Our analysis revealed that heritability of root traits such as root system depth and seminal root length was moderate to high (r2 = 0.52 and r2 = 0.93, respectively), enabling further assessment of increasing numbers of recombinant genotypes. The results demonstrate the suitability of GrowScreen-Rhizo 3 to phenotype a range of plant species characterized by various growth habits, including crop, niche, and wild plant species. We conclude that GrowScreen-Rhizo 3 will contribute significantly to the development of phenotyping pipelines for the identification of candidate genotypes with improved resource use efficiency and to pre-breeding processes of climate-resilient crops.
Robot-assisted hysterectomy (RAH) has been progressively introduced in gynecologic surgery, yet nationwide data describing its uptake and early efficiency outcomes remain limited. We described trends in surgical route for hysterectomy within France and evaluate the length of hospital stay (LoS) according to surgical route and center expertise in robot-assisted surgery (RAS). All total hysterectomies (excluding vaginal) performed in France between January 2020 and December 2024 were identified from the national Programme de Médicalisation des Systèmes d'Informations (PMSI) registry. Procedures were categorized as open, laparoscopic hysterectomy (LH), or RAH and stratified by indication (endometriosis, other benign conditions, malignancy) and by center expertise in RAS, including multidisciplinary RAS centers. Primary outcomes were surgical volumes by approach and LoS. Among 196,050 hysterectomies, LH remained the predominant approach; nevertheless, the proportion of RAH increased steadily across all indications over time, mainly at the expense of open surgery. This increase was more pronounced in high-volume and multidisciplinary RAS centers. Across indications, LoS was consistently shorter after minimally invasive surgery than after open hysterectomy. LoS following RAH was comparable to LH and decreased progressively over time. In experienced and multidisciplinary RAS centers, RAH was associated with the lowest LoS for benign indications. These nationwide, real-world findings show that RAH is increasingly being integrated into minimally invasive hysterectomy pathways within France, with LoS comparable to laparoscopy and shorter than open surgery. Our results support the role of RAS expertise and multidisciplinary organization in optimizing early clinical and operational outcomes during the adoption of gynecologic RAS.
Pancreatic cancer (PC), particularly pancreatic ductal adenocarcinoma (PDAC), is a highly lethal malignant tumor with poor prognosis, limited early screening strategies, and high chemoresistance. Periodontal disease (PD), a prevalent chronic inflammatory disorder caused by oral microbiota dysbiosis, has been increasingly linked to systemic diseases, including cancer. This review summarizes the epidemiological evidence, potential pathogenic mechanisms, and clinical management implications of the association between PD and PC. Epidemiological studies, including meta-analyses, cohort studies, and case-control studies, consistently demonstrate that PD (especially moderate-to-severe periodontitis and combined gingivitis-periodontitis) is associated with an increased risk of PC incidence and mortality, with significant population heterogeneity (more prominent in middle-aged and elderly individuals, males, and those with comorbid diabetes). Specific periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, play key roles in this association, showing dose-response relationships and preceding PC onset. Mechanistically, PD contributes to PC development through multiple interconnected pathways: translocation and colonization of periodontal pathogens in pancreatic tissue, induction of precancerous lesions (e.g., acinar-to-ductal metaplasia), activation of inflammatory signaling pathways (TLR4/NF-κB, Wnt/β-catenin), immune dysregulation and tumor immune escape, microbiota imbalance and carcinogenic metabolite accumulation (e.g., acetaldehyde, nitrosamines), and induction of chemoresistance (via cytidine deaminase-mediated gemcitabine inactivation or Notch1 pathway activation). Clinically, this association provides novel perspectives for PC prevention and management: integrating periodontal health assessment into PC risk screening, developing non-invasive diagnostic biomarkers (oral microbiota, miRNAs, saliva metabolites), optimizing treatment strategies (targeted antibiotics, probiotics, phage therapy), and establishing a multidisciplinary collaboration (MDT) model involving dentistry, oncology, gastroenterology, and microbiology. In conclusion, PD is a potentially modifiable risk factor for PC, and oral health management may serve as a cost-effective strategy for PC prevention and improved prognosis. Future prospective studies are needed to confirm the causal relationship and standardize clinical practices for this cross-organ association.
Invasive aspergillosis (IA) is a major cause of morbidity and mortality in immunocompromised children. Pediatric data are limited, and treatment guidelines often rely on adult studies. This study aimed to assess clinical characteristics and treatment outcomes of pediatric IA. We conducted a retrospective cohort study of pediatric patients (0-18 years) diagnosed with IA at a tertiary center in Türkiye between 2010 and 2022. Data on demographics, underlying conditions, Aspergillus species, antifungal susceptibility, treatment regimens, and outcomes were analyzed. Survival analysis was performed using Kaplan-Meier curves. Fifty-five children met criteria for proven (69%) or probable (31%) IA after excluding 22 possible cases. Median age was 8.6 years; mortality did not differ significantly by age, sex, or underlying condition. Hematologic malignancies were the most common comorbidity (35%). Aspergillus fumigatus was the predominant species (57%), and no antifungal resistance was detected. Classical risk factors; central venous catheter use (53%), neutropenia (51%), and recent chemotherapy (35%) were frequent but showed no association with mortality. Lung involvement was the most common presentation (71%), followed by sinus (31%) and central nervous system involvement (13%). Thirty-day mortality was 11%, 12-week mortality was 20% (11/55), and overall mortality reached 29%. Pediatric IA remains associated with substantial morbidity and mortality, although outcomes in this cohort were more favorable than those reported in many prior pediatric series. No single clinical, microbiological, or radiological factor reliably predicted mortality, underscoring the complexity of risk stratification. Early diagnosis and timely antifungal therapy remain essential, and multicenter prospective studies are needed to optimize treatment approaches.
Methods using environmental nucleic acids have become highly effective for monitoring aquatic biodiversity, with an array of suitable use cases, including metrics for fisheries assessment. Traditional methods for assessing fish populations often rely on invasive techniques with limited spatial and temporal coverage. Environmental DNA (eDNA) has revolutionised biomonitoring assessments by facilitating species detection and abundance estimation in a noninvasive and indirect manner. Environmental RNA (eRNA) offers a promising complement by capturing the transcriptional activity of organisms. In addition, the study of eDNA methylation may provide an avenue for detecting the regulation of the expression of genes of interest. This review highlights the opportunities to unlock the full potential of eDNA and eRNA in supporting sustainable fisheries assessment by offering noninvasive, alternative and complementary methods for age assessment, sex identification and reproductive stage, physiological and health status, genetic structure and stock identification. By integrating these innovative approaches with traditional methods, a more comprehensive understanding of aquatic ecosystems can be achieved, ultimately leading to improved fisheries conservation and management decision-making.
Takayasu arteritis is a chronic large-vessel vasculitis that predominantly affects young women and may lead to severe vascular complications. This case series is noteworthy because it describes Takayasu arteritis revealed by severe cardiovascular and neurovascular complications, including ischemic stroke and advanced heart failure, in young women without traditional cardiovascular risk factors. We report three cases of Takayasu arteritis observed at Ibn Rochd University Hospital in Casablanca in 2024. The median age was 38 years. Two patients presented with ischemic stroke, while one presented with advanced heart failure. Clinical examination revealed upper limb claudication, dyspnea on exertion, decreased or absent radial pulses, carotid bruits, and significant blood pressure asymmetry between upper limbs. Laboratory investigations showed an inflammatory syndrome with elevated C-reactive protein and erythrocyte sedimentation rate, as well as inflammatory anemia. The diagnosis was confirmed by multimodal non-invasive vascular imaging, including Doppler ultrasound, computed tomography (CT) angiography, magnetic resonance (MR) angiography, and positron emission tomography (PET) scan, fulfilling the 2022 American College of Rheumatology classification criteria. All patients received high-dose corticosteroid therapy (1 mg/kg/day) followed by progressive tapering. Standard treatment for heart failure was initiated when indicated, and anticoagulation or antiplatelet therapy was prescribed according to the presence of embolic events. Clinical and biological improvement was observed in all patients, with partial neurological recovery and a significant reduction of inflammatory markers. Takayasu arteritis may present with highly polymorphic clinical presentations, including severe cardiovascular and neurovascular complications as initial manifestations in young women without traditional risk factors. Early recognition through multimodal non-invasive vascular imaging is essential to establish the diagnosis promptly and initiate appropriate treatment, thereby reducing the risk of irreversible complications.