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Early and accurate detection of plant leaf diseases is an essential requirement for precision agriculture, given their severe impact on global food security. While much has been done recently, many deep learning-based approaches will still fail in real-world tests because of challenges such as background clutter, differences in illumination, occlusion, or the fact that visual&#x2002;symptoms for these diseases can be very subtle early on. Traditional CNN- and Transformer-based architectures generally lack accurate lesion localisation and interpretability, hindering their practical deployment in agricultural decision-support tools. To address these issues, we present LDDHybridNet, a region-based, explanation-friendly deep learning framework that can identify leaf disease at an early, accurate stage. It then applies preprocessing steps guided by ROI, based on leaf segmentation from the U-Net, followed by a compact CNN-based spatial feature-extraction framework. We arrange spatial feature embeddings extracted from lesion regions into an ordered sequence and employ a Bi-LSTM with attention to model structured contextual dependencies, allowing progression-aware feature learning without requiring actual temporal image sequences. Lastly, Grad-CAM-based post-hoc explainability is employed to interpret model decisions, enabling transparent visualisation of disease-relevant regions. We conduct extensive experiments on the PlantVillage benchmark and the FieldPlant dataset and show that LDDHybridNet consistently outperforms representative CNN, transformer, and hybrid baselines across multiple evaluation metrics. Although the near-ceiling performance on PlantVillage reveals the dataset's artificial nature, the proposed framework achieves 95.37% accuracy under real-world field conditions and 92.84% on weak-lesion early-stage samples, demonstrating the method's robustness and early-stage detection potential. The performance boosts are statistically significant (P&#x2009;<&#x2009;0.01). In general, LDDHybridNet is an interpretable and robust deep learning framework for leaf disease detection, which can support data-driven crop protection and precision agriculture&#x2002;applications.

This study aims to evaluate the outcomes of a new PND initiative designed to optimize healthcare delivery in a highly consanguineous population. A descriptive study was conducted at a major tertiary referral center for genetic diseases in Saudi Arabia with a large scope objective to improve the existing prenatal diagnosis (PND) process. Consequently, a new prenatal workflow featuring a structured checklist, a dedicated prenatal board, and enhanced genetic counseling has been implemented since September 2023. The study included all prenatal cases with a documented autosomal recessive (AR) disease. The program processed 1128 cases, with 952 cleared by the prenatal checklist. In total, the board has discussed 160 variants of unknown significance (VUS), of which 122 (76%) were upgraded to likely pathogenic/pathogenic. Remarkably, the prenatal checklist enhanced patient safety and reduced serious harm incidents, while the prenatal board facilitated precision medicine by leveraging collective expertise in variant interpretation. This initiative significantly improved the healthcare, safety, and accessibility of PND services. The prenatal board and checklist streamlined decision-making, minimized errors, and enhanced patient outcomes. The model provides a cost-effective approach to preventing genetic diseases in highly consanguineous populations and serves as a replicable framework for similar settings worldwide.

Periodontitis, a chronic inflammatory disease, is increasingly prevalent among young people and impairs their quality of life. Adverse childhood experiences (ACE), depressive symptoms, and suboptimal health status (SHS) are linked to health risks and chronic diseases, but their interrelationships with periodontitis in Chinese young adults remain unclear. This study aimed to explore associations among these factors. From December 2024 to May 2025, 2,888 participants (aged 18-35) from Tongji Hospital completed surveys on demographics, ACE, depressive symptoms, and SHS. Periodontitis was diagnosed according to the 2018 criteria. Simple, parallel, and chain mediation models were used, controlling for age, sex, marital status, and smoking. Periodontitis prevalence was 25.00% and higher in married individuals (P&#xa0;<&#xa0;0.001) and smokers (P&#xa0;=&#xa0;0.004). ACE correlated positively with depressive symptoms (r&#xa0;=&#xa0;0.28, P&#xa0;<&#xa0;0.001), SHS (r&#xa0;=&#xa0;0.19, P&#xa0;<&#xa0;0.001), and periodontitis (r&#xa0;=&#xa0;0.16, P&#xa0;<&#xa0;0.001). Mediation analyses showed: Simple model: Depressive symptoms and SHS partially mediated the effect of ACE on periodontitis (indirect effect&#xa0;=&#xa0;0.011 for both). Parallel model: Only SHS significantly mediated the effect (indirect effect&#xa0;=&#xa0;0.011). Chain model: ACE was related to periodontitis via "depressive symptoms &#x2192; SHS" (indirect effect&#xa0;=&#xa0;0.010), with significant direct and indirect effects. ACE associated with higher periodontitis risk in young people. This association included both a direct link between ACE and periodontitis, and an indirect link through the chain pathway of "depressive symptoms &#x2192; SHS"; among these pathways, SHS was a key mediator. The study was registered in the Chinese Clinical Trial Registry (ChiCTR) with the registration number ChiCTR2500103464. Childhood trauma can exert long&#x2010;term impacts on health, including oral health. This study involving 2,888 Chinese young adults aged 18&#x2010;35 found that 25% of the participants had periodontitis. Those who experienced childhood abuse, neglect, or family issues showed a higher association with the disease. The research revealed two pathways linking early trauma to periodontitis: a direct association and an indirect chain of &#x201c;depressive symptoms &#x2192; suboptimal health status (e.g., persistent fatigue).&#x201d; While depressive symptoms played a role, suboptimal health status was the critical mediator. Higher periodontitis rates in married individuals and smokers may relate to stress or lifestyle factors. The findings suggested that early identification of childhood trauma, combined with interventions targeting mental health or overall well&#x2010;being (e.g., counseling, health management), could be more effective than oral care alone in prevention. This underscored the association between early&#x2010;life experiences and long&#x2010;term health and the need for integrated interventions.

Therapeutic plasma exchange (TPE) is being increasingly utilized in the clinical management of severe rheumatic immune diseases, providing an effective means for rapidly removing pathogenic autoantibodies and inflammatory mediators. However, the non-selective nature of this technique can also lead to the unintended clearance of concomitantly administered antirheumatic drugs, potentially compromising therapeutic efficacy and disease control. Therefore, effective management of potential drug removal process during TPE and the implementation of individualized risk assessment are crucial for optimizing treatment outcomes in patients undergoing TPE. The variability in the extent of drug removal during TPE is primarily determined by their distinct pharmacokinetic characteristics, necessitating the establishment of a systematic, evidence-based strategy for adjusting drug administration regimens in patients receiving TPE treatment. This review synthesizes current evidence from 65 studies on the removal of antirheumatic drugs during TPE, identifying key determinants influencing clearance rates, including volume of distribution, protein binding, molecular size, and elimination half-life. Our analysis reveals that the risk of drug removal exists as a continuous spectrum: large monoclonal antibodies (e.g., rituximab, natalizumab), characterized by a large molecule size, low volume of distribution, with which mostly confined to the vascular space, are cleared with high efficiency. This finding supports the clinical recommendation of administering such drugs after TPE. For drugs with limited direct evidence, we propose a predictive model based on fundamental pharmacokinetic parameters to estimate their removal risk and guide clinical decision-making. Based on this evidence, we have constructed a stratified clinical management framework. It aims to maintain effective therapeutic drug exposure levels during chronic TPE therapy and to provide a rationale for the judicious application of TPE in overdose scenarios. Implementing this pharmacokinetic-informed, risk-adapted individualized strategy is important for ensuring treatment continuity, enhancing patient safety, and advancing empiricism-based therapy towards precision medicine.

Rare diseases affect small, dispersed populations and are often studied through multisite designs where equity-relevant demographic data are essential for inclusive recruitment and accurate interpretation. This study examined how sociodemographic variables are collected and reported in rare disease research and evaluated their alignment with the PROGRESS-Plus framework, which outlines Place of residence, Race/ethnicity/culture/language, Occupation, Gender/sex, Religion, Education, Socioeconomic status, social capital, and additional "Plus" factors such as age and disability status. A systematic review of peer-reviewed articles was conducted alongside an environmental scan of demographic instruments from governmental, health-system, academic, and rare disease organizations. Screening and extraction coded variables as reported, indirectly derivable, or not reported and compared them with established standards. Of 647 records identified, 37 met inclusion criteria. Reporting was dominated by age and sex, while most other equity-relevant variables including gender identity, sexual orientation, race/ethnicity, distinctions-based Indigenous identity, socioeconomic position, language, migration, disability/function, religion, occupation, and social capital, were inconsistently captured. Environmental scan instruments were more comprehensive, revealing a capture-to-reporting gap. Demographic reporting in rare disease research is heterogeneous and insufficient for equity-focused analyses. A concise, standards-aligned sociodemographic dataset is needed to improve transparency, comparability, and detection of inequities across rare disease populations.

Government-led repurposing programmes are reshaping the division of labour in pharmaceutical innovation. A new power drafted into the European Union pharmaceutical reform package will allow the European Medicines Agency (EMA) to add new therapeutic indications to marketed medicines without the marketing authorization holder's consent. Companies oppose this power, but in weighing up enacting the power, society has a poor understanding of its potential to help patients. This study offers the first empirical assessment of the promise of the power. It analyses 198 medicines from 12 years, comparing EMA-authorized labels with those authorized by the US Food and Drug Administration and a leading reference for off-label uses. Sixty-seven per cent of the medicines have at least one additional use supported by clinical evidence, yielding 320 potential new uses. Of these, 39 per cent are for new diseases and 61 per cent for new patient cohorts, a third of the latter concerning paediatric populations. Commentators generally omit discussing repurposing for new patient cohorts, even though it is a focus of the European Commission. The study's results suggest that the power could be used to authorize a meaningful number of evidence-based uses, especially those already authorized in the USA, while also revealing a policy synergy for neglected populations.

Portal hypertension (PH) is one of the major complications of liver cirrhosis, traditionally assessed using invasive methods such as the hepatic venous pressure gradient (HVPG). Soluble endoglin (sENG), a marker of endothelial dysfunction and fibrosis, has been proposed as a non-invasive biomarker of various liver diseases. This study aimed to evaluate serum sENG concentrations in cirrhotic patients with PH and investigate its relationship with PH severity, alcohol consumption, and smoking. Serum concentrations of sENG were measured in clinically well-examined patients with liver cirrhosis (n&#x2009;=&#x2009;60, age range 24-82 years) with PH classified as mild, moderate, or severe according to the HVPG values measured invasively using the classical wedge technique. sENG concentrations were also compared to healthy controls (n&#x2009;=&#x2009;54). Liver enzyme activities, alcohol consumption history, and smoking habits were also recorded to assess their association with sENG. sENG concentrations were significantly higher in patients with PH compared to healthy controls (6.31; 5.14-7.30 vs. 3.70; 3.24-4.20 ng/mL, p&#x2009;<&#x2009;0.001) but did not correlate with the severity of HVPG-diagnosed portal hypertension. A moderately significant correlation was observed between sENG concentrations and GGT activities (p&#x2009;<&#x2009;0.001). Alcohol consumption, but not smoking, was associated with higher serum sENG concentrations (p&#x2009;<&#x2009;0.01). Based on our results, sENG appears to be a non-invasive marker of endothelial dysfunction/fibrosis in cirrhotic patients with PH, particularly in alcohol-related liver disease. Although it does not reflect PH severity and thus cannot be used as a diagnostic tool, it has the potential for early disease detection and risk prediction as a screening component in non-invasive approaches in clinical hepatology.

The classification of functional brain networks plays an important role in the diagnosis of neurodegenerative diseases, brain decoding and other fields. Functional brain networks can effectively reflect the functional connection relationships between brain regions or neurons and accurately represent brain activities. Therefore, a large number of problems related to the classification of functional brain networks have been studied. However, the traditional functional brain network merely measures the static correlation between brain regions or neurons in a simple way, and does not reflect the causal transmission effect between brain regions. This directionality is crucial for the regulatory relationship between brain regions. Furthermore, since the brain is constantly in a state of dynamic change, the dynamics of functional connectivity also plays a very important role in the classification of functional brain networks. Therefore, we propose a classification framework named Dynamic Directed Propagation Networks (DDPN) for functional brain networks considering the dynamic directed propagation mechanism. This method effectively captures the dynamics and directionality of the dynamic directed brain network and further improves the classification accuracy of the functional brain network. To verify the effectiveness of the proposed method, we conduct experiments on real datasets. The experiments show that the proposed method improved by 3.1-4.1% compared with state-of-the art methods in two datasets.

In this review we comprehensively discuss organic cation transporter novel 1 (OCTN1), encoded by the SLC22A4 gene as a member in the solute carrier 22 (SLC22) family, which facilitates the cellular transport of diverse cationic and zwitterionic substrates. OCTN1 is highly expressed in many vital organs in humans, where it facilitates absorption and distribution of both endogenous compounds and therapeutic drugs. Among its substrates, ergothioneine (EGT) serves as the primary antioxidant and anti-inflammatory molecule, underscoring the essential role of OCTN1 in cellular defense and inflammation control. Genetic polymorphisms in SLC22A4 significantly alter OCTN1 expression, substrate affinity, and drug pharmacokinetics, with strong associations to susceptibility and treatment outcomes in human diseases. Insights from knockout models revealed that OCTN1 deficiency leads to reduced EGT availability, heightened oxidative stress, and aggravated inflammation, particularly in the tissues such as intestine, liver and lung. Moreover, OCTN1 activity is dynamically regulated by epigenetic modifications, cytokines, and hormones, linking it to immune modulation and disease progression. Put together, OCTN1 plays a defined role via high-affinity EGT transport, while its broader transport capacity and pharmacological relevance remain under investigation, with possible - though not yet established - implications for inflammation-associated biomarker development.

Accurate detection of KRAS codon mutations is essential for precision oncology in colorectal cancer (CRC), yet conventional liquid biopsy methods often lack sufficient sensitivity for rare ctDNA variants, particularly in early diseases. We developed a three-dimensional (3D) plasmonic KRAS microarray integrating blocked recombinase polymerase amplification with plasmon-enhanced fluorescence. Quencher-modified blocking probes suppress wild-type DNA while selectively enabling mutant signal amplification. A single primer-probe set per codon allows comprehensive detection of all substitutions within KRAS codons 12/13, 61, and 146. The platform achieved detection down to 1 fM by direct hybridization and 100 zM after blocked amplification, exceeding conventional PCR and next-generation sequencing sensitivity. Codon-level specificity was validated in CRC cell lines, with distinct signals for each mutation. Clinical analysis of 58 patients showed 100% concordance between tissue, plasma, and urine in mutation-positive malignant cases when sufficient input was available, indicating accurate reflection of tumor profiles. In benign tumors, detection was rare despite tissue mutations, likely due to limited ctDNA release.This plasmonic microarray enables ultra-sensitive, specific, and non-invasive detection, supporting early diagnosis, minimal residual disease monitoring, and longitudinal CRC management.

SMARCB1-deficient sinonasal carcinoma (SDSC) is a rare, highly aggressive malignancy with limited therapeutic options and no established preclinical models. Here, single-nucleus RNA sequencing (snRNAseq), spatial transcriptomics, and ex vivo patient-derived tissue slice culture (TSC) were combined to resolve intratumoral heterogeneity, niche organization, and treatment vulnerabilities in an index SDSC. snRNAseq identified three malignant subpopulations, including two specialized states marked by ALDH1A1 and NTN4. Spatial profiling mapped these states to distinct niches. The ALDH1A1+ compartment localized to a basal-associated niche with intermingled p63-positive basal cells adjacent to stroma, showed reduced proliferative activity, and displayed stem-like transcriptional features. Ex vivo drug testing revealed a striking response: the mTOR inhibitor Sapanisertib induced extensive tumor necrosis and was associated with near-complete depletion of ALDH1A1+ and NTN4+ states, accompanied by strong stress/apoptosis signatures and reduced endothelial cells. In an additional retrospective cohort of 12 SDSC, ALDH1A1 was present in all cases with heterogeneous spatial patterns and higher levels in recurrences. Mesothelin was expressed in the index case and a subset of tumors, supporting mesothelin-directed therapeutic strategies.

Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism presenting with acute liver failure, cirrhosis, or neurologic involvement. Liver transplantation (LT) is the definitive treatment; however, data remain limited, particularly from regions reliant on living donor LT (LDLT). We retrospectively analyzed a prospectively collected transplant database, identifying all patients (&#x2265;&#x2009;14 years) who underwent LT for WD between January 2001 and December 2023. Data on demographics, LT indications, disease characteristics, pre-transplant therapy, complications, and outcomes were collected. Survival was assessed using Kaplan-Meier methods, and neurologic outcomes from clinical documentation. Forty-one patients underwent LT for WD (median age: 23 years; 51.2% female). Ascites was present in 68.4%, encephalopathy in 32.4%, and hepatocellular carcinoma in 5.1%. Acute liver failure was the initial presentation in 17.9%. LDLT comprised 53.7%. Acute cellular rejection occurred in 29.7% but was manageable; no patient required re-transplantation. Neurologic involvement was present in 17.1%, with 71% improving post-LT. One-, five-, and ten-year survival rates were 94%, 94%, and 82%. LT for WD yields excellent long-term survival. Neurologic improvement occurred in most Neuro-Wilson patients, supporting LT even in neurologically affected cases. LDLT plays a crucial role in regions with limited deceased donors.

Ongoing neurodevelopmental care is essential for children with congenital heart disease (CHD). Understanding delivery and uptake of neurodevelopmental care pathways can inform implementation and resource planning. This study applied simulation modelling to explore outcomes from a neurodevelopmental care pathway for children with CHD. The model was developed using data from a Queensland program to explore health service interactions for neurodevelopmental screening, formal assessment, and early intervention, up to five years. Modelling was intended to provide a baseline understanding of the pathway, rather than evaluating against a reference standard. Hypothetical scenarios explored how changes in screening and referrals influenced the identification of developmental concerns, and how developmental concern severity affected intervention referrals. Based on available data, 58% of the cohort remained under routine surveillance and 25% had accessed early intervention for one or more developmental delays. Scenarios defined by increased screening projected up to 55% of the cohort having a developmental concern identified during screening and 45% having a developmental delay identified following assessment. Simulation modelling was useful for understanding outcomes from a neurodevelopmental pathway and how differences in screening and assessment affected health service interactions. Findings may inform policy and resource planning for future neurodevelopmental pathways. This study shows that simulation modelling is a useful approach for evaluating a neurodevelopmental care pathway for children with CHD, to understand movement through neurodevelopmental screening, assessment, and interventions. Scenario-based modelling provides insights into factors influencing pathway engagement, contributing evidence to strengthen understanding of service gaps and areas where improvements can most effectively impact engagement and resourcing. This study identifies neurodevelopmental screening as the most influential stage impacting downstream outcomes, underscoring its importance as a strategic intervention point. This study's approach provides a general framework for evaluating similar pathways and a potential baseline for assessing future policy or service changes.

Lactate, an energy source and metabolic by-product, has been implicated in cancer progression, but its role in colorectal cancer (CRC) remains incompletely understood. This study investigated the clinical significance, biological effects, and transcriptomic responses of CRC cells to lactate. In human CRC specimens, lactate levels were positively associated with advanced clinical stage and poorer disease-free survival. Functional assays showed that lactate promoted malignant cellular behaviors in both SW480 and HCT116 cells, while pH-control experiments suggested that these effects were not merely due to extracellular acidification alone. RNA sequencing in SW480 cells identified 1,418 differentially expressed genes after lactate treatment. GO and KEGG analyses revealed alterations in multiple metabolic and signaling pathways. qRT-PCR validated the alterations of representative genes, including HK2, VEGFA, JUNB, CCNB1, MAPK4, and COX2. In addition, flow cytometry showed activation of NF-&#x3ba;B and HIF-1&#x3b1; signaling following lactate treatment, and pharmacological inhibition of either pathway significantly attenuated the lactate-induced malignant phenotypes. Together, these findings provide transcriptomic and functional evidence that lactate promotes malignant phenotypes in CRC cells and offer exploratory mechanistic insights into the involvement of NF-&#x3ba;B and HIF-1&#x3b1; signaling.

Hidradenitis suppurativa (HS), an inflammatory skin disorder characterized by painful nodules and abscesses, has varying prevalence among different races/ethnicities. This study explored the social drivers of health, burden, and impact of HS among different racial and ethnic groups. An online, cross-sectional survey was conducted among adult patients with HS (September 2023-December 2023) in the USA. Patients were recruited through HS Connect (patient advocacy group) and AmeriSpeak (US national sample panel). Descriptive data were collected using patient-reported outcome measures and de novo questions about patients' disease knowledge and perception, healthcare access and utilization, impact on quality of life (QoL), and social impact. All analyses were descriptive and stratified by racial/ethnic groups. The study included 583 patients (mean age, 34.8&#xa0;years; 95.5% female) representing a range of racial backgrounds: Black or African American (n&#x2009;=&#x2009;273; 46.8%), white (n&#x2009;=&#x2009;236; 40.5%), Two or More Races (n&#x2009;=&#x2009;47; 8.1%), American Indian or Alaska Native (n&#x2009;=&#x2009;18; 3.1%), Asian (n&#x2009;=&#x2009;7; 1.2%), and Native Hawaiian and Other Pacific Islander (n&#x2009;=&#x2009;2; 0.3%). Ethnic representation also varied (Hispanic/Latino&#x2009;=&#x2009;n&#x2009;=&#x2009;76; 13.0%). Patients of all races and ethnicities reported considerable QoL impact (Dermatology Life Quality Index, EQ-5D-5L), with results for smaller subgroups (n&#x2009;<&#x2009;10) included for descriptive completeness only and not intended for comparison with other groups. During flaring, most patients used over-the-counter products/medications (54.2%) or nonmedical intervention/home remedy (56.9%) Up to 36.5% of patients reported challenges in procuring food, utilities, medicine/healthcare, phone, clothing, or childcare when needed in the past year. Among those who paid out-of-pocket for their HS treatment, 55.6% reported that it stopped them from visiting a healthcare provider for treatment. The findings indicate a high burden and impact of HS across all races and ethnicities. Patients reported social drivers of health and challenges with healthcare utilization, indicating the need for integrating social workers and care management teams in dermatology practice, which could facilitate improved care of patients with HS. Hidradenitis suppurativa is a painful skin condition that causes lumps and abscesses. It affects people of all races and ethnicities but is more common in Black or African American individuals. This study surveyed 583 adults in the USA to understand how hidradenitis suppurativa affects people from different racial and ethnic backgrounds. Our focus was on how the disease impacts their daily lives, their ability to access healthcare, how often they visit doctors, their quality of life, and their mental and emotional well-being. Most people said that hidradenitis suppurativa lowers their quality of life and makes daily activities harder. During flaring, many used home remedies instead of seeing a doctor. People suffering from hidradenitis suppurativa also reported trouble getting basic needs such as food, medicine, and transportation. These challenges occurred among patients from different racial and ethnic groups; results for very small subgroups (Asian, Native Hawaiian/Other Pacific Islander) are reported descriptively only and should not be interpreted as representative of these groups or compared with other groups. The research underscores the importance of improving awareness and tailoring care for people with hidradenitis suppurativa, particularly those facing barriers to healthcare.

To evaluate finerenone-associated adverse events (AEs) and to investigate the association between finerenone use and renal injury via data mining of the Food and Drug Administration Adverse Event Reporting System (FAERS). To minimize statistical bias, the data extraction period was set from database inception (2004) to provide a stable background for disproportionality analysis. Four disproportionality algorithms (ROR, PRR, BCPNN, and MGPS) and stricter case-screening methods were employed to improve analytical precision. Additionally, a clinical priority evaluation was conducted to rank clinical risks and surveillance levels for these AEs. Supplementary analysis was performed to assess the relationship between finerenone and renal injury, as well as associated risk factors. A total of 1316 finerenone-related reports were identified. 30 AEs were detected as significantly positive signals, with most being related to renal function (15 PTs, 50%), blood pressure (5 PTs, 16.67%), and blood potassium (4 PTs, 13.33%). Among them, blood glucose increased, blood creatine increased, and flank pain were new potential AEs. Acute kidney injury, hyperkalemia, renal impairment, glomerular filtration rate decreased, blood creatinineincreased, blood potassium increased, and hyponatremia exhibited moderate clinical priority levels and warrant further study. Signals reflecting renal injury were detected in patients regardless of baseline nephropathy. Male sex, taking more than 3 drugs, and using amlodipine may be risk factors for finerenone-related nephrotoxicity. These results highlight new finerenone-related AEs, provide ranked guidance for pharmacovigilance through clinical priority evaluation, and clarify factors that influence renal injury, providing guidance for individualized treatment and improved drug safety.

Cutaneous gene therapy has the potential to treat a wide range of skin disorders, but effective delivery remains limited by the skin's barrier properties and immune surveillance. Here, we identify AAVrh32.33 as a potent vector for targeting dermal stromal compartments. Following systemic administration in mice, AAVrh32.33 mediated robust and durable transgene expression, with preferential targeting of dermal fibroblasts and hair follicle bulge cells. Expression peaked at one month and persisted for up to two years, highlighting its suitability for chronic conditions. To reduce immunogenicity, a dominant CD8+ T cell epitope was disrupted, generating the IDP&#x394; variant. This modification attenuated peptide-specific T cell responses while preserving stromal transduction. In human skin explants, IDP&#x394; achieved high levels of gene expression, primarily in dermal fibroblasts and precursors, confirming translational relevance. Finally, vectors encoding CCL17, CCL20, and CCL22 demonstrated localized targeted therapeutic gene delivery in both healthy and inflamed skin, underscoring the feasibility of using this platform to reshape local immune responses. Together, these findings establish AAVrh32.33 and IDP&#x394; as promising platforms for durable cutaneous gene therapy, with direct applications in diseases such as vitiligo where long-term modulation of the dermal microenvironment is essential.

Long-tail segmentation is a crucial challenge in computer vision, where most models prioritize common head classes over rare tail classes. This problem is particularly prominent in retinal vessel segmentation, as conventional approaches often struggle to overcome underrepresented faint vessels, noise-induced boundary ambiguity, and excessive parameters that prohibit portable deployment. To address these challenges, we introduce LFU-Net, a lightweight and clinically applicable method for long-tail retinal vessel segmentation. It integrates a three-component ensemble: a Frequency-Aware Encoder with a Multi-Branch Frequency Convolution block, which uses wavelet decomposition to suppress noise and retain details; Hierarchical frequency-token enhanced Low-Rank Adaptation, which efficiently enhances the representation of tail classes (faint vessels) with minimal parameters; and a Recursive Residual Attention Fusion module to ensure vascular topological continuity. Extensive experiments on four public benchmark datasets demonstrate that LFU-Net achieves competitive performance compared to recent relevant models. Its lightweight nature supports real-time inference on portable devices. Ablation studies confirm the improvement contribution of each core component, indicating its potential utility in early disease detection when clinical resources are limited.