Stigma impacts outcomes across stigmatizing conditions, including substance use disorders (SUDs). Recent policy changes give patients rapid access to clinical notes in the electronic health record (EHR), which may include stigmatizing language. The objective of this study was to assess the perspectives of women with history of pregnancy and SUDs on typical language used in clinical notes. Women with a history of pregnancy and SUD were recruited through an online crowd-sourcing platform. Respondents viewed examples of clinical language and answered survey questions about perceived stigma. An inductive approach was used to analyze open-text responses, and themes were developed. Three hundred seventy survey respondents wrote a response to at least one open-text question. Thematic analysis yielded 4 major themes: (1) anticipation of future stigma facilitated by EHR documentation can affect patients' care decisions for themselves and their babies; (2) documented SUD history could have short- and long-term effects on patients' experience of stigma and discrimination, especially in labor and delivery; (3) phrases using "denies" and quotes within quotation marks could be perceived as stigmatizing and decrease trust in providers; (4) nonstigmatizing language and acknowledgement of recovery in notes can facilitate positive experiences for patients, but patients want more acknowledgement of recovery and positive language. Electronic health record documentation can modulate stigma experiences for women during and after pregnancy through stigmatizing language in clinical notes and facilitating discrimination, decreasing trust in providers and negatively impacting health outcomes. Raising providers' awareness of nonstigmatizing and positive language or implementing technology to prompt nonstigmatizing terminology could contribute to positive experiences among women with a history of pregnancy and SUD.
Large language models (LLMs) are transforming medicine, yet their use has been largely confined to back-end administrative tasks, leaving their potential for real-time patient interaction critically unexplored. This study aimed to address this gap by developing and evaluating Spine-GPT, a novel AI assistant built on multi-layered prompt engineering to conduct pre-consultation interviews in the field of spine surgery and enhance clinical decision-making. A two-phase study was conducted. Phase 0 involved simulation-based evaluation using 24 fictional clinical scenarios assessed by three board-certified spine surgeons across seven domains (adaptive questioning, complaint comprehension, diagnostic accuracy, justification clarity, investigation appropriateness, red-flag recognition, and professional tone) on 5-point Likert scales. Phase 1 was a prospective clinical pilot study involving 60 patients, allocated to a control group (n = 30) receiving conventional consultations and an intervention group (n = 30) using Spine-GPT before face-to-face appointment. The primary outcome was active surgeon history-taking time. Secondary outcomes included information completeness, red-flag detection, surgeon and patient satisfaction. In simulations, Spine-GPT demonstrated high performance, with mean scores exceeding 4.0 out of 5 across all evaluation domains. In the clinical study, the AI-assisted group achieved a 31.3% reduction in active surgeon history-taking time (11.47 min vs. 7.88 min; p < 0.001). This efficiency gain was achieved alongside a significant increase in information completeness (11.7%-point increase; p < 0.001). All three predefined red-flag cases were correctly identified. Surgeon and patient satisfaction were significantly higher in the intervention cohort (p < 0.001), with 70% of the AI-generated summaries requiring no edits. This study provides proof-of-concept that a prompt-engineered LLM can safely increase clinical efficiency while simultaneously improving the quality of data collection in a specialized surgical practice. By structuring its reasoning process to be transparent, the system functions as an explainable "probabilistic partner" rather than an uninterpretable "black box," helping to bridge the gap between automated inference and clinician trust. This work ultimately positions the clinician not as a passive bystander to automation, but as a critical editor and beneficiary of machine-reasoning, supporting the new paradigm for human-AI collaboration in clinical care.
Cell migration is a critical process in development, homeostasis, and disease. While cell migration in vitro is well investigated, much less is known about migration deep within tissues, largely due to limitations associated with deep cell imaging in tissues. In this study, we investigated cell migration history in vivo by developing a strategy based on recording cell trails formed by fusion of fluorescent protein and collagen secreted by migrating cells. By engineering different cell lines to express either fluorescent protein-fused Col1a1 or Col1a2 we identified trails formed in normal mouse tissues as well as primary tumors and metastatic organ sites. Analyses of the trail patterns revealed the paths taken by migrating cells and regions that suggest group trails, including trails along vascular adventitia. These results demonstrate that cell migration history can be traced in mouse models through postmortem analysis of normal and cancerous tissues.
Early-life adversity is widely linked to accelerated biological ageing, yet it remains unclear whether such associations reflect exposure during sensitive developmental periods, the cumulative burden of exposures, or temporal proximity to later outcomes. Here, we leverage life-history theory and a life course framework to nuance how the timing of adverse childhood experiences (ACEs) becomes biologically embedded through epigenetic ageing. Using longitudinal data from the Future of Families and Child Wellbeing Study (N=1,974), we apply statistical learning and structured life course modelling to test sensitive period, cumulative risk, and recency hypotheses across multiple domains of adversity (poverty, instability, deprivation, and maltreatment). We find that adversity exposure during specific developmental periods, rather than cumulative burden or recent exposure, are most strongly associated with epigenetic age acceleration in late childhood ([Formula: see text]=0.003). Moreover, the timing and direction of these effects vary by adversity type. Epigenetic ageing is in turn associated with later health-related risks ([Formula: see text]=0.29, SE=0.06; [Formula: see text]=1.62, SE=0.27) and demographic behaviour ([Formula: see text]=0.21, SE=0.08; [Formula: see text]=0.22, SE=0.11), and further mediates the association between ACEs and outcomes in young adulthood, particularly for BMI ([Formula: see text]=0.003, SE=0.002, [Formula: see text]=11%). These findings demonstrate that childhood adversity may be linked to biological ageing in developmentally specific and domain-dependent ways, with certain developmental periods appearing more sensitive to adversity exposure than others.
Captive breeding plays an important role in the conservation of large carnivores. Yet, factors influencing offspring survival remain poorly quantified. Using long-term reproductive records from the Jaguar Conservation Fund, Brazil, we examined sources of variation in cub survival within a highly productive jaguar (Panthera onca) population. We analysed 34 litters (66 cubs) produced by 10 females and 11 males between 2014 and 2025. Data were evaluated using both litter-level binomial mixed-effects models and individual-level survival analyses. Overall cub survival was high (86.4%), but varied predictably with maternal parity and management context. Litters from multiparous females showed near-complete survival, whereas primiparous litters experienced significantly lower survival probabilities. Paternal presence at birth was associated with reduced cub survival and elevated early mortality risk. In contrast, a history of maternal hand-feeding was associated with improved survival. Proximity to humans showed no statistically supported effect after accounting for other variables. Survival analyses restricted to the first 90 days post-birth confirmed that these factors influenced early-life mortality risk rather than cumulative losses over time. Random effects for dam and sire identity explained little additional variation, indicating that observed differences in survival were largely attributable to identifiable life-history and management factors rather than persistent individual effects. Together, these results demonstrate that high reproductive success in captive jaguars is compatible with structured human intervention, and that early postnatal survival is shaped primarily by maternal experience and social context. By identifying specific, actionable risk factors, this study provides evidence-based guidance for refining captive management strategies for large felids.
Harmful freshwater cyanobacteria, such as Microcystis, are increasingly reported in brackish estuaries, yet the extracellular mechanisms that allow freshwater colonies to withstand salt stress in nature remain unresolved. This study combined field surveys with in situ bottle and enclosure experiments to examine how colony size, extracellular polysaccharides (EPS), and upstream nitrogen availability shape the salinity tolerance of Microcystis transported from upstream lakes to the brackish water. Larger colonies were more abundant under higher salinity in the estuary, and redundancy analysis showed that salinity and water temperature were the primary correlates of colony size distributions. In situ suspended bottle experiments demonstrated that larger colonies maintained positive growth at higher salinity thresholds than small colonies, and that EPS accumulation increased with colony size. Small colonies showed rapid EPS synthesis under low-salt stress but were unable to sustain this response once salinity exceeded 10-12‰. Enclosure experiments further revealed that low nitrogen availability in upstream freshwater promoted the formation of larger colonies, enhanced EPS production, and strengthened physiological resistance to salt stress during downstream transport. These findings indicate that colony morphology and EPS act as key mediators of Microcystis survival along freshwater-estuarine gradients, and that nitrogen limitation upstream can facilitate bloom persistence in brackish water. Integrating colony size, EPS dynamics, and nutrient regimes into monitoring and management frameworks will improve early warning capacity for bloom propagation in estuaries under increasing anthropogenic and climate-driven pressures.
暂无摘要（点击查看详情）
Diabetes mellitus (DM) has a strong genetic component and is a known risk factor for several hand conditions. We aimed to examine whether DM in first-degree relatives is associated with an increased risk of hand surgical diagnoses. A retrospective cohort study. Data were collected from a population-based cohort in southern Sweden (Malmö Diet and Cancer Study (MDCS)). Family relationships were obtained through the Swedish Multi-Generation Register and healthcare diagnoses from the National Patient Register. 30 446 individuals (60% female) aged 45-73 years were included from the MDCS. The primary outcome was any diagnosis within the 'diabetic hand' category; carpal tunnel syndrome, ulnar nerve entrapment, trigger finger, Dupuytren's disease and thumb base osteoarthritis, identified through International Classification of Diseases, tenth revision codes. Logistic regression models were used. In the index study population, 4 150 (14%) had ≥1 hand surgical diagnosis. In unadjusted models, DM in the index individual and first-degree relatives was associated with an increased risk of developing hand surgical diagnoses (OR 1.14, 95% CI 1.06 to 1.22). After adjusting for confounders, only DM in the index individual remained significantly associated with the diabetic hand (OR 1.23, 95% CI 1.13 to 1.33). In diagnosis-specific analyses, an association persisted between having ≥1 sibling with DM and Dupuytren's disease (OR 1.39, 95% CI 1.09 to 1.76), and between having ≥1 child with DM and carpal tunnel syndrome (OR 1.18, 95% CI 1.00 to 1.39). While DM in the index individual was consistently associated with a higher risk of multiple hand surgical diagnoses, DM in first-degree relatives did not significantly influence the risk after adjustments. Exceptions included an association between ≥1 sibling with DM and Dupuytren's disease, and ≥1 child with DM and carpal tunnel syndrome. Future research should further explore potential genetic factors contributing to these conditions.
Auditory dysfunction such as tinnitus is a common sequelae of traumatic brain injury (TBI), and has been associated with neurobehavioral outcomes, including cognitive decline, depression, and anxiety. Few studies have examined associations between concussion history and tinnitus independent of confounding by blast injury or occupational noise exposure. This study investigated concussion history and tinnitus among former professional American-style football (ASF) players, and evaluated whether tinnitus mediates associations between concussion history and neurobehavioral outcomes. This cross-sectional study included former ASF players who contracted with a professional league after 1960 and completed self-administered questionnaires between 2019-2025. Surveys assessed football exposure, auditory dysfunction, and mental health. Cumulative head injury exposure was measured using self-reported concussion signs and symptoms during play. Tinnitus was self-reported and assessed concurrently with validated measures of perceived cognition, depression, and anxiety. Logistic regression evaluated associations between concussion symptom history and tinnitus, and linear regression models assessed mediation and interaction effects. Among 1085 participants (mean age 57.9 ± 13.5 years; 32.4% Black; 6.1 ± 3.7 seasons), greater concussion symptom history was associated with increased odds of tinnitus (highest vs. lowest quintile: OR = 2.90; 95%CI 1.91-4.43; p < 0.0001). Tinnitus did not mediate associations between concussion symptom history and neurobehavioral outcomes. However, associations with perceived cognition (p-interaction = 0.1), depression (p-interaction < 0.01), and anxiety (p-interaction < 0.01) were larger among participants reporting tinnitus. Greater concussion symptom history was associated with increased reporting of tinnitus, and neurobehavioral associations were stronger among those with tinnitus. Clinicians should consider tinnitus when evaluating long-term cognitive and mental health outcomes following repeated head injury.
Men who have sex with men (MSM) have a disproportionately high syphilis burden. As anal ulcers are less visible than penile ulcers, we examined whether MSM practicing receptive or versatile versus insertive anal intercourse were more likely to be diagnosed at a later syphilis stage. Using cross-sectional data from MSM enrolled in the Network Epidemiology of Syphilis Transmission (NEST) study, we evaluated the associations between sexual positioning (exclusive bottom, versatile bottom, or versatile vs. exclusive top or versatile top) and three outcomes: 1) syphilis stage diagnosed at baseline (secondary or latent vs. primary), 2) lifetime history of syphilis, and 3) history of syphilis in the past 12 months. Overall, 655 MSM enrolled in NEST; 599 had complete data on sexual positioning and syphilis stage at baseline. Of these, 57 had syphilis at baseline (Analysis 1), 506 had complete data on lifetime history of syphilis (Analysis 2), and 377 had complete data on history of syphilis in the past 12 months (Analysis 3). Among MSM with syphilis at baseline, those who practiced receptive or versatile versus insertive anal intercourse had 13 (95% CI=1.4-123) times the odds of being diagnosed with secondary or latent stage syphilis. Sexual positioning was not associated with syphilis history in the lifetime or past 12 months. These findings suggest that differences in sexual positioning may influence the stage at which syphilis is diagnosed among MSM. Further research in larger samples is needed to better understand these differences and their underlying mechanisms and to assess potential implications for clinical detection and diagnosis.
Hydrocephalus treatment via shunting to the peritoneum, atrium, or pleural space may be contraindicated in pediatric patients with complex surgical history or small size. We aim to describe experience and outcomes of ventriculogallbladder shunt (VGBS) placement. A retrospective review was performed of all patients (<18 y) who underwent VGBS placement at a single quaternary children's hospital (January 1, 2014-October 31, 2025). Patients were identified by Current Procedural Terminology code and operative records. Demographics, past medical history, prior shunt history, indication for VGBS, subsequent revisions, and duration were collected. Descriptive statistics were utilized. Five male patients were identified with a median age at VGBS placement of 6.9 mo (interquartile range [IQR] 5.9, 9.0). Four patients developed hydrocephalus secondary to neonatal intraventricular hemorrhage and one from obstructive intracranial malignancy. All patients had intra-abdominal pathology: three necrotizing enterocolitis, one omphalocele and intestinal atresia, and one dysfunctional peritoneum. One patient had a ventriculoperitoneal shunt, ventriculoatrial shunt, and ventriculopleural shunt prior to VGBS, three patients had prior ventriculoperitoneal shunt, and one patient had no prior shunts. Of the four patients with prior shunt placement, the median age at first drainage procedure was 4.1 mo (IQR 3.0, 4.8) with a median of 4.5 revisions (IQR 3.5, 7.5) prior to VGBS. Three of the five VGBS remain functional after 2.4, 4.8, and 7.2 y with two patients undergoing conversion to ventriculopleural shunts (1.4 and 6.8 y postplacement). The gallbladder is a feasible and vital consideration for distal ventricular shunt placement in children of small size and/or intra-abdominal pathology which prohibit traditional locations.
Chorea is a hyperkinetic movement disorder with a broad differential diagnosis, ranging from acute symptomatic causes to slowly progressive neurogenetic diseases. While Huntington's disease (HD) remains the most prevalent hereditary form, numerous other genetic disorders may mimic its clinical presentation. A major diagnostic challenge arises in patients with a seemingly negative family history, which can obscure the suspicion of a genetic etiology. In patients with sporadic chorea, the potential contribution of genetic testing to the diagnostic process has not yet been systematically analyzed. We conducted a retrospective analysis of 81 patients presenting with chorea as a prominent symptom at the movement disorders outpatient clinic between 2013 and 2024. Clinical data, family history, laboratory results, imaging, and genetic analyses were evaluated. Genetic testing included a chorea-related gene panel and, if unremarkable, whole-exome or whole-genome sequencing. Out of 81 patients, 44 presented with slowly progressive chorea and unremarkable family history of HD or chorea-related syndromes. After exclusion of secondary etiologies (n = 8), 36 patients remained, of whom 30 (83, 33%) received a confirmed genetic diagnosis. HD was the most frequent diagnosis (n = 20), followed by rare genetic disorders such as Spinocerebellar Ataxia Type 17 (n = 2), Wilson's Disease (n = 2), Ataxia with Oculomotor Apraxia Type 2 (n = 1), C9orf72-related Neurodegeneration (n = 1), Choreoacanthocytosis (n = 1), KMT2B-related Dystonia (n = 1), ERCC4-related Neurodegeneration (n = 1), and Glutaric Acidemia Type 1 (n = 1). These findings support the systematic use of genetic testing-even in apparently sporadic cases-and suggest that the prevalence of hereditary choreatic disorders, may be significantly underestimated.
The postmenopausal bone health reflects the influence of various factors that have been in effect throughout life and hormonal regulation is among them. The aim of the current study is to investigate the effect of pregnancies and other factors related to female reproductive health on bone mineral density and the incidence of fractures in the postmenopausal period. We performed a case-control retrospective analysis in a group of 977 postmenopausal women from the RACOST-POL cohort. In the study group, there were 894 (91.5%) women who had at least one delivery and breastfeeding was reported by 845 (86.5%) women. Bone mineral density (FN T-score) was not related to pregnancies and history of lactation, but correlated positively with age at menopause and with time of reproductive period. Low-energy fractures were reported by 286 women, which consists 29.3% of the study group. There was no difference in fracture prevalence between women who delivered (29.4%) or not (27.7%). Also the breastfeeding status was not related to fracture prevalence (28.9% in the subgroup declaring lactation and 31.8% in the others). Women with fractures had earlier age of menopause and shorter time of reproductive period in comparison to subjects without fractures (48.3 ± 5.2 vs. 49.5 ± 4.7 ys.; p < 0.001; OR 0.95 (95% CI: 0.93 - 0.98), and 34.1 ± 5.5 vs. 35.5 ± 4.9 ys.; p < 0.001; OR 0.95 (95% CI: 0.93 - 0.98), respectively). Additionally, fracture prevalence in the 'early menopause' (below 45 ys) subgroup was significantly higher (39.1%) than in all the others (27.8%) with OR 1.66 (95% CI: 1.13 - 2.42). Our study did not show a significant association between history of pregnancies or lactation and the skeletal status in the postmenopausal period. However, a shortened period between menarche and menopause and an earlier age at menopause may have a negative impact on bone health in later life. Presented results complement the knowledge on a wide and diverse spectrum of factors modifying bone health in postmenopausal women.
Combined oral contraceptives are widely used and generally considered safe. However, they have been associated with arterial thrombosis, including myocardial infarction, particularly in women with cardiovascular risk factors. This case adds to the limited literature highlighting the potential for combined oral contraceptive-induced myocardial infarction in individuals without traditional cardiovascular risk factors. A 28-year-old non-smoking Iranian woman with no significant medical history presented with 11 h of typical anginal chest pain radiating to the left arm and interscapular area. Electrocardiography revealed ST-segment elevations in leads V2-V5, and cardiac biomarkers confirmed myocardial infarction. She had been taking a second-generation combined oral contraceptive containing 150 µg levonorgestrel and 30 µg ethinyl estradiol for 13 years. Emergent coronary angiography demonstrated a thrombotic occlusion in the mid-left anterior descending artery without evidence of underlying atherosclerosis. Successful reperfusion was achieved via balloon angioplasty without stenting. The patient remained stable, was discharged on optimal medical therapy, and advised to discontinue combined oral contraceptives. At 3-month follow-up, cardiac Computed Tomography Angiography revealed a patent left anterior descending artery with no residual stenosis, and echocardiography showed improved systolic function. This case underscores the potential for thrombotic myocardial infarction in young women using combined oral contraceptives, even in the absence of conventional risk factors. It highlights the importance of considering hormonal contraceptive history in the diagnostic workup of acute coronary syndromes in young females. In addition, it demonstrates that Balloon angioplasty without stent placement may be effective in selected cases of non-atherosclerotic thrombotic occlusion.
We report a rare case of isolated choroidal inflammation in a patient with a history of treated choroidal melanoma who subsequently developed cutaneous melanoma and underwent adjuvant treatment with pembrolizumab. The patient presented with a new choroidal lesion adjacent to the treated choroidal melanoma. Differential diagnosis included recurrence of choroidal melanoma, metastases from the cutaneous melanoma or pembrolizumab-associated choroidal inflammation. Ultrasound findings suggested an inflammatory aetiology and the patient was treated with an intravitreal dexamethasone implant. One month later, the lesion had regressed and visual acuity improved. Pembrolizumab, an immune checkpoint inhibitor, can cause ocular immune-related adverse effects, including choroidal inflammation. This case underscores the importance of distinguishing between inflammatory and metastatic lesions, particularly in patients with a history of ocular malignancy. Early recognition and appropriate treatment with steroids can prevent irreversible vision loss and multimodal imaging is crucial in such cases.
Spinocerebellar ataxia type 10 (SCA10) is a rare, autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia and, frequently, seizures. While it is linked to Native American and East Asian ancestry, no cases have previously been reported in Guatemala. We evaluated a large Guatemalan family at the Mayo Movement Disorder Clinic with index case of a 42-year-old Native American man with genetically confirmed SCA10. Assessment included clinical history, the Scale for the Assessment and Rating of Ataxia (SARA), neuroimaging, and molecular genetic testing. Additionally, neurofilament light chain (NfL) levels were measured in plasma and cerebrospinal fluid (CSF) from index symptomatic SCA10 case, unaffected relatives, two healthy controls and two symptomatic SCA3 cases. The index patient presented with slowly progressive balance impairment, dysarthria, and limb ataxia starting in his 30s. Genetic testing confirmed a pathogenic ATTCT repeat expansion in the ATXN10 gene. A strong family history was noted, with several affected siblings and a wheelchair-bound mother, though notably, no family members experienced seizures. CSF NfL levelin the index case (650.7 pg/mL) was elevated compared to an unaffected relative and healthy controls. This report identifies the first SCA10 family in Guatemala, extending the known geographic distribution of the disorder in Central America. Our findings also provide the first data on CSF NfL in SCA10, suggesting its potential utility as a biomarker for monitoring disease progression.
This study presents a comprehensive examination of coastal dune morphology, migration, and internal structures in Nitzanim, Israel. Our approach integrated Ground Penetrating Radar (GPR) and satellite analysis to understand their evolution and internal architecture. The methodology involved multi-frequency GPR (500 MHz, 250 MHz, and 100 MHz) for subsurface imaging and multi-temporal Landsat, Sentinel-2, and aerial/UAV imagery, with NDVI (Normalized Difference Vegetation Index) analysis for long-term vegetation cover and dune migration monitoring. Results demonstrate a clear trend of decreasing vegetation cover across the study area from 1995 to 2025, which coincides with increased dune mobility and shifts in dune position, with peak migration rates occurring after a localized anthropogenic change: the construction of an artificial lake in 2005. For example, the northern dune's brink line shifted approximately 71 m eastward from its 1995 position, with its southern segment becoming completely exposed by 2015 due to vegetation loss. Concurrently, processed GPR profiles revealed a coherent sequence of quasi-linear internal reflectors within the dune body, with shallow reflections near the crest exhibiting a distinct eastward inclination, suggesting the prevailing direction of past sediment transport. The consistency of these structural elements across different GPR frequencies highlighted the robustness of the multi-frequency GPR methodology employed. Furthermore, the study revealed a relationship between vegetation dynamics and the internal stratification visible in GPR data. While high NDVI values in 1995 correlated with sand accumulation and a visible accumulation line, a reduction in vegetation cover between 2010 and 2025 coincided with an apparent decrease in vertically accreted stratification in GPR profiles, suggesting a relative increase in lateral dune migration during the most recent phase. The combined multidisciplinary approach offers crucial insights into the complex history of dune stabilization, reactivation, and migration in the Nitzanim coastal dunes. It contributes to process understanding in aeolian geomorphology, informing environmental management and conservation strategies in dynamic desert landscapes.
To identify risk factors and examine associations between colorectal cancer (CRC) status and modifiable and non-modifiable risk factors among patients diagnosed in Oman, considering the existence and increase of incidence and prevalence of these risk factors. A multicentre case-control study. Sultan Qaboos University Hospital and the Royal Hospital in Muscat, Oman. Patients diagnosed with CRC (n=166) and controls (n=166). A questionnaire adapted from the Colon Cancer Family Registry and other previously published studies was used to collect data on sociodemographic characteristics, modifiable and non-modifiable CRC risk factors and coexisting morbidities. Univariable and multivariable logistic regression analyses were performed to examine associations between CRC status and independent variables. Multivariable analysis demonstrated significant associations between CRC status and several risk factors. Smoking was associated with a fourfold increased risk of CRC (adjusted OR (aOR): 4.35, 95% CI 2.26 to 8.36). Higher body mass index was also associated with increased CRC risk (aOR: 2.42, 95% CI 1.23 to 4.76), while individuals with a family history of CRC, including first-degree relatives (biological parents, siblings and children) and second-degree relatives (grandparents, uncles and aunts) had more than double the risk (aOR: 2.10, 95% CI 1.15 to 3.82). Also, polyps had double the risk (aOR 2.61, 95% CI 1.40 to 4.84) In addition, CRC was more common among patients with diabetes (aOR 2.70, 95% CI 1.52 to 4.80), hypertension (aOR 4.13, 95% CI 2.03 to 8.42) and inflammatory bowel disease (aOR 3.48, 95% CI 1.13 to 10.67). Considering the existence of non-modifiable risk factors and the increase in incidence and prevalence of modifiable risk factors of CRC in Oman, the findings of this study underscore the need for targeted awareness initiatives, risk-based screening and early surveillance, particularly among high-risk groups. The results also support integrating smoking cessation, weight management and optimal control of chronic diseases into national CRC prevention programmes to reduce the overall CRC disease burden.
The Platform Vector-Gene Therapy (PaVe-GT) program is a National Institutes of Health (NIH) initiative that aims to develop adeno-associated virus (AAV) gene therapies for four monogenic rare diseases, two organic acidemias and two congenital myasthenic syndromes. PaVe-GT's platform-based approach identifies and diminishes redundancies and applies efficiencies in preclinical, clinical, and regulatory activities. The program's hypothesis is that implementing these efficiencies can accelerate clinical trial initiation. Based on its platform-centric experience and public-serving mission, the PaVe-GT program actively shares its scientific and regulatory learnings with the public to benefit the development of similar gene therapy products for rare diseases. PaVe-GT's first investigational AAV gene therapy candidate is AAV serotype 9 human propionyl-CoA carboxylase alpha subunit (AAV9-hPCCA) for propionic acidemia caused by PCCA deficiency, which received initial feedback from the Food and Drug Administration (FDA) in an INitial Targeted Engagement for Regulatory Advice on CBER/Center for Drug Evaluation and Research (CDER) ProducTs (INTERACT) meeting. Upon further product development that took into consideration the FDA's initial advice, the program obtained the Agency's feedback in pre-investigational new drug (IND) (Type B) and Type C meetings. Here, we share our experience from these meetings, including strategy, preparation, pre- and post-meeting feedback from the FDA, and lessons learned during the AAV9-hPCCA regulatory process, which the program plans to apply across the PaVe-GT platform. Topics discussed in the regulatory meetings included animal model and efficacy studies, toxicology study plans, manufacturing of the investigational AAV product, and clinical trial design. The main lessons learned from the pre-IND and Type C meetings for AAV9-hPCCA are: (1) Pharmacology/Toxicology studies in a single rodent species are sufficient for filing an initial IND; (2) FDA feedback guides product quality improvements and early development of a quantitative potency assay; (3) use of biomarkers as potential surrogate endpoints in a future efficacy trial benefits from collection of data in the natural history study and the first-in-human Phase 1/2 study; and (4) evidence from the Phase 1/2 clinical trial could be leveraged to support a license application. Lightly redacted regulatory documents and comprehensive templates developed by the PaVe-GT team are available on the PaVe-GT website.
The geographic origin of endourological innovation is undergoing a fundamental and measurable transformation. This editorial maps a decisive shift across four domains: suction-integrated ureteroscopy and ureteral access sheaths (UASs), single-use flexible ureteroscopes, laser lithotripsy platforms, and robotic flexible ureteroscopy, using four independent indicators: Food and Drug Administration (FDA) regulatory clearances, international patent filings, citation impact, and guideline representation. The turning point for suction-enabled ureteroscopy was 2016, when Well Lead Medical (China) obtained the first FDA 510(k) clearance for a suction-capable UAS, with Chinese manufacturers subsequently dominating new approvals in this category. In single-use ureteroscopy, between 2022 and April 2026, Chinese manufacturers accounted for 47% of FDA 510(k) clearances, matching the USA in absolute count for the first time in the history of the field. In laser lithotripsy, China's share of annual patent filings grew from <10% to >35% between 2015 and 2024. In robotic flexible ureteroscopy, Asian manufacturers are now entering a field previously defined by European and Turkish platforms. Analysis of the EAU Urolithiasis Guidelines 2026 (n = 312 publications, from 2018) reveals that European publications have historically dominated citations (37.8%), followed by Asia (27.9%) and North America (19.2%); strikingly, Asian publications surpassed Europe in annual citation share by 2025, driven by a dramatic rise since 2023. For European and North American stakeholders, the appropriate response is not defensiveness but strategic engagement, through international collaboration, cross-border training, and institutional adaptability, in the shared interest of improving patient care worldwide.