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Identification of divergent PTPN11 mutations in canine histiocytic sarcomas reveals evidence of an independent clonal origin

Background Histiocytic sarcoma (HS) is a rare but highly aggressive neoplasm in humans, with limited knowledge on indicators markers and no standardized treatment. Dogs naturally develop HS, offering a powerful comparative model. Activating mutations in PTPN11 , affecting two recurrent hotspots (E76 and G503), are the most frequent drivers of canine HS and are strongly associated with the disseminated form (DHS). While DHS is typically considered metastatic, we hypothesize that multiple independent tumor clones may arise within the same individual. Methods We investigated clonal heterogeneity in 38 dogs affected with DHS presenting tumors in both abdominal and thoracic organs. PTPN11 hotspot mutations were analyzed by high-sensitivity droplet digital PCR (ddPCR) to detect low-abundance variants. The frequency of divergent mutations between tumor sites was used to infer the proportion of cases arising from independent clonal origins. Results Divergent PTPN11 mutations were directly observed in 3 of 28 dogs with PTPN11 -mutated tumor pairs. After correcting for the limited detectability inherent to hotspot-based analysis, we estimated that, in this cohort, up to 24–45% of DHS cases may harbor clonally independent PTPN11 mutations in distinct tumors. In addition, analysis of somatic mutations and copy number variants by Next Generation Sequencing (NGS) in two cell lines derived from the same patient confirmed the independent origin of the clones. Conclusions Our findings suggest that a significant numbers of dogs with DHS develop several genetically distinct HS lesions either simultaneously or within a short time interval. This need to be confirmed in larger cohorts but this clonal diversity challenges the assumption that DHS is predominantly metastatic and has major implications for prognosis, therapeutic strategies, and the use of canine HS as a comparative model for human disease. Further exploration of clonal evolution in HS is warranted to improve treatment approaches in both species.

Effect of targeted versus fixed dosing of nafamostat mesylate on filter life in patients undergoing continuous renal replacement therapy

Correction: miR-217 inhibits triple-negative breast cancer cell growth, migration, and invasion through targeting KLF5

Long-term monitoring of heavy metals and physicochemical characteristics in leachate-affected waters of Upper Lake, Bhopal

Repeatability and reproducibility of a clinical device for Brillouin microscopy to measure the biomechanics of the anterior segment of the eye: In vivo tests

Purpose We performed a prospective study to assess the repeatability and reproducibility of the novel Brillouin Optical Scanning System (BOSS ® ) in measuring the biomechanical properties of the cornea and crystalline lens in vivo, to determine device utility in a clinical setting. Methods Adult study participants underwent standard ophthalmic exams to confirm eligibility. At two separate visits to the clinic, monocular lens scans and corneal scans (one point and seven points, respectively) were performed three times on each of three BOSS devices, operated by different technicians. The measured Brillouin parameters per person included the lens stiffness and the stiffnesses (e.g., “Mean”, “Minimum”) across the seven corneal points. Results were combined across participants to calculate the coefficients of variation (CVs) for repeatability (within each device) and reproducibility (across devices), along with the repeatability and reproducibility limits (2.8 times the respective standard deviations). Results Eleven of the 33 participants (ages 24–72 years; 15 females) had keratoconus (5 with prior crosslinking, 3 without crosslinking, and 3 post-keratoplasty); the other 22 participants were visually normal. There were no adverse events. The average lens stiffness was 3.33 ± 0.052 GPa (mean ± SD), with an overall repeatability CV of 1.6%, with values ranging from 3.35 ± 0.037 GPa with a CV of 1.1% to 3.30 ± 0.071 with a CV of 2.1% across the separate devices. The mean corneal stiffness was 2.83 ± 0.031 GPa, with an overall repeatability CV of 1.1%, ranging from 2.85 ± 0.015 with a CV of 0.5% to 2.81 ± 0.036 with a CV of 1.3% across devices. The reproducibility CVs were 2.1% and 1.6% for lenses and corneal Means, respectively. Conclusions The study results demonstrated consistent stiffness values for both lenses and corneas within and between the three BOSS devices tested. The study shows that this device could be a useful new biomechanics-measuring tool for applications in ophthalmology.

Deep learning-based early warning of tailings storage facility instability using Sentinel-1 and Radarsat-2 InSAR calibrated with a geomechanical model

Abstract This study advances the science and application of Interferometric Synthetic Aperture Radar (InSAR) for monitoring tailings storage facilities (TSFs) by integrating multi-scale and multi-source satellite data with geomechanical modelling and deep learning to detect ground movement precursors to failure. A novel calibration strategy combining geomechanical finite element (FE) predictions with InSAR measurements is introduced to dissect the origins and expressions of known InSAR limitations related to phase unwrapping. By investigating different InSAR processing algorithms along with data from both commercial (Radarsat-2) and public (Sentinel-1) sensors, the study demonstrates the extent to which these limitations can be overcome. During periods of rapid or non-linear deformation, such as buttress construction over the TSF, Persistent Scatterer InSAR (PS-InSAR) time series show more sensitivity to phase unwrapping errors, making phase ambiguities more readily observable. The extent to which such ambiguities can be identified and calibrated using physics-based finite element model predictions is demonstrated in this study. In contrast, Intermittent Small Baseline Subset (ISBAS) processing reduces the visible expression of phase ambiguities through inherent signal averaging (i.e. multi-looking), while maintaining a higher spatial density of deformation measurements. An uncertainty analysis for both InSAR approaches links accuracy to SAR signal distortions and uncertainties in FE model parameters. Finally, the capabilities of the deep learning early-warning framework capable of ingesting multi-source InSAR datasets, including different sensors, geometries and decomposed motion components are presented. Embedding-based integration of line-of-sight and decomposed Radarsat-2 (RS2) InSAR data reveals that orbit configuration and resolution directly influence predictive performance. Specifically, the horizontal deformation components provide the clearest precursors to failure, outperforming line-of-sight and vertical motion components. The combined use of RS2-InSAR, Sentinel-1 PS-InSAR, Sentinel-1 ISBAS, FE modelling and deep learning offers a promising framework for TSF monitoring. This integrated approach promises to reduce uncertainties inherent in individual methods and to significantly improve the ability to reduce risks of environmental and economic losses.

Integrating biomedical HIV prevention in schools: Protocol for a systematic review of interventions for adolescent girls and young women in sub-Saharan Africa

Introduction Despite global progress in reducing HIV incidence, adolescent girls and young women in sub-Saharan Africa remain disproportionately affected. Biomedical HIV prevention tools such as pre-exposure prophylaxis, condoms and HIV testing are effective but underutilized, especially within facility-based models. Schools represent consistent and scalable contact points for reaching adolescent girls and young women, yet evidence on the feasibility, accessibility and effectiveness of school-based biomedical HIV prevention interventions remains limited. Objective This systematic review aims to synthesize evidence on how school-based programs implement, deliver and achieve outcomes in HIV prevention interventions involving pre-exposure prophylaxis, condom and HIV testing for adolescent girls and young women in sub-Saharan Africa. Materials and methods This review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Eligible studies will include randomized and non-randomized trials and qualitative research published between January 2015 and December 2025. Databases to be searched include PubMed, Embase, PsycINFO, CINAHL and the African Index Medicus, together with relevant grey literature sources (WHO, UNAIDS, UNICEF and PEPFAR). Two reviewers will independently screen titles, abstracts, and full texts, extract data, and assess risk of bias using appropriate tools. Quantitative data will be synthesized using meta-analysis where feasible, while qualitative findings will undergo thematic synthesis. Outcomes of interest include the feasibility, accessibility, and effectiveness of school-based HIV prevention interventions. Discussion This review will provide a comprehensive synthesis of evidence on biomedical HIV prevention interventions delivered in school settings for adolescent girls and young women in sub-Saharan Africa. Findings will highlight implementation process, barriers, facilitators and equity considerations. Trial registration number: PROSPERO CRD420251249595

Towards a better understanding of adverse life experiences in autism and attention-deficit/hyperactivity disorder

Abstract Individuals with autism and/or Attention-Deficit/Hyperactivity Disorder (ADHD) face greater adversity, which is typically associated with negative life outcomes (e.g., depression), but potentially, adaptive strengths (e.g., resilience). Little is known about the types of adversity experienced by autistic/ADHD adults, the processes underlying this increased risk, and the subsequent impact of adversity. Further, almost nothing is known about whether and how strengths arise from adversity in neurodevelopmental conditions. Autistic/ADHD adults ( N  = 123), living in the UK or USA, reported their adverse life experiences, including the role of autism/ADHD, and any resulting strengths. Data were analysed using codebook thematic analysis. Overall, eight themes (11 subthemes) highlighted four factors underlying adversity (Cognitive, Social, Emotional, and Sensory), two major types of adverse experiences (Marginalisation and Mistreatment), and two long-term outcomes of adversity (Health Outcomes and Strength Outcomes). Autistic/ADHD individuals experience an array of adversities across settings (including schools, homes, and workplaces), in part due to autism/ADHD-associated cognitive, social, emotional, and sensory factors. Whilst there are negative consequences of adversity, we also highlight that adverse life experiences may confer strengths. These findings underscore the need for tailored interventions to mitigate the susceptibility to adversities and subsequently reduce the negative impact of adversities in autism/ADHD.

Autobiographical memory of validating and invalidating consultations is associated with recall capacity for health information

Managing chronic pain involves cognitive and emotional challenges that may affect treatment adherence. Patients’ ability to remember clinician advice is therefore important. Clinician behaviours may influence these processes. To investigate whether recounting autobiographical memories of perceived validating (vs. invalidating) healthcare experiences influences subsequent recall of health-related information in people living with chronic pain, 245 adults with chronic pain (≥3 months) were recruited online. Eligibility criteria included: age ≥ 18 years, fluent in English, no hearing difficulties or mental health conditions, and at least one healthcare visit in the previous two years. Participants were quasi-randomly assigned to describe either a validating or invalidating consultation they had previously experienced. Before and after this task, participants rated their pain intensity and pain-related fear. Participants then listened to 20 health messages and were later asked to recall them in an incidental memory test. The primary outcome was incidental recall of health messages, operationalised as the likelihood of recalling each of the 20 messages. Secondary outcomes included pain intensity and pain-related fear. Recall was analysed using a binomial generalized linear mixed-effects model accounting for individual differences (pain intensity, pain-related fear, immersion in the task, age, sex, and pain duration).Participants who described a validating consultation were more likely to recall health messages than those in the invalidating condition (19% higher odds of recalling each message, based on model estimates). The association was not mediated by change in pain-related fear. These findings indicate that remembering validating consultations might boost retention of health information, highlighting clinician-validation as a potential strategy to support cognitive functioning in people living with chronic pain.

Umbilical cord blood biomarkers of neuronal injury in sleep-disordered breathing during pregnancy

Mapping multilevel barriers impacting the performance of Ethiopia’s Community-Based Health Extension Program: A scoping review

Background Ethiopia’s Health Extension Program (HEP) aims to improve primary care access through community-based delivery of essential preventive and promotive services. Despite progress, some health outcomes remain suboptimal, underscoring the need to optimize HEP implementation. Identifying barriers of the HEP and its Health Extension Workers (HEWs) is critical for enhancing program effectiveness. This scoping review aims to identify and synthesize evidence on the barriers impacting the performance of the Ethiopian HEP and HEWs. Methods A comprehensive search strategy was conducted across multiple databases, including PubMed, EMBASE, Web of Science, and relevant institutional websites, as well as hand searches via Google Scholar and Google engine, to identify both published and unpublished documents (documents (government reports and policy documents (strategic plans, program reviews, annual performance reports), development partner publications, doctoral dissertations, and masters theses) related to the HEP. The review encompassed studies published since January 2003. Data extraction was performed using Atlas.ti software version 7.5.18, which facilitated the collection of verbatim excerpts and the application of thematic coding to highlight key findings. The results are organized and presented through thematic analysis, focusing on multi-dimensional barriers and challenges. Results The review reveals multi-dimensional barriers, including a misalignment between the HEP’s preventive design and the community’s demand for curative services, which undermines community trust and program acceptance, and gender-imbalanced workforce, which creates barriers to service delivery in certain cultural contexts. Additional barriers include a lack of training and retention strategies, and digital literacy and access gaps which further impede effectiveness of the program. Excessive workloads, non-health tasks, and poor living conditions, divert HEW’s focus from their primary responsibilities. Weak community engagement, inadequate integration of Traditional Birth Attendants (TBAs), and inefficiencies in model family development limit the program’s impact. Misconceptions in the community, resource constraints, fragmented stakeholder interactions, ineffective supervision, governance issues, and political interference directly impede performance. Conclusion The HEP faces deeply entrenched, multi-dimensional barriers that limit its potential to achieve optimal health outcomes. Key policy recommendations include integrating curative services, ensuring a balanced gender mix in the workforce, improving working conditions and expanding community engagement. Further research is needed to quantify barriers, assess their impact, and identify key influencing factors, with stakeholder engagement and implementation research being essential for developing effective solutions.

Efficacy and safety of invasive laser acupuncture (650 and 830 nm) on knee osteoarthritis: A pilot randomized clinical trial

This pilot study explored the safety and efficacy of invasive laser acupuncture (ILA) using two wavelengths (650 and 830 nm) compared with a sham laser in patients with knee osteoarthritis (KOA). This randomized, parallel-arm, patient- and outcome assessor-blinded, placebo-controlled, single-center clinical trial was designed with three groups (control, 650, and 830 nm), and 45 participants were randomly allocated in a ratio of 1:1:1. All participants were treated with ILA on the more affected side at SP9, SP10, ST34, ST35, EX-LE2, EX-LE4, and GB34 for 10 minutes per session, twice weekly, for a total of 12 sessions over 6 weeks. The primary outcome was the change in pain visual analog scale (VAS) score at rest and during activity at baseline (Visit 1) versus 1 week after intervention completion (Visit 13). Secondary outcomes included VAS scores after six treatments (Visit 7) and 6 weeks after intervention completion (Visit 14), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L), patient’s global assessment, rescue medication dosage, and responder rate. Changes in the VAS scores at rest (p = 0.0044, Visit 13; p = 0.0001, Visit 14) and during activity (p = 0.0038, Visit 13; p < 0.0001, Visit 14) were significantly different among the three groups. Significant differences were also observed in WOMAC total (p = 0.0278, Visit 7; p = 0.0485, Visit 13; p = 0.0051, Visit 14), pain (p = 0.0073, Visit 7; p = 0.0210, Visit 13; p = 0.0038, Visit 14), function subscale (p = 0.0055, Visit 14), and EQ-5D-5L scores (p = 0.0131, Visit 14). No ILA-related adverse events or significant changes in vital signs or laboratory results were observed during the study. ILA at 650 and 830 nm showed preliminary signals of short-term pain reduction. However, these preliminary findings should be confirmed in larger, rigorously designed clinical trials. Trial registration CRIS registration number: KCT0008860; registered on 10/11/2023 ( https://cris.nih.go.kr/cris/search/detailSearch.do/25506 ).

Diagnostic and prognostic values of differentially expressed genes in canine mammary carcinoma: An integrated bioinformatics analysis

Background Canine mammary carcinoma (CMC) is a common tumor in unspayed dogs and poses a significant health concern for animals. This study aimed to identify differentially expressed genes (DEGs) between CMC and adjacent healthy mammary tissue through an integrated RNASeq bioinformatics analysis that combined an independently generated dataset from the present study, CPA-UN (CPA-UN), composed of RNA-seq data obtained from CMC and matched normal mammary tissue samples, with publicly available GEO datasets generated using next-generation sequencing (NGS). Candidate genes associated with diagnostic and prognostic potential were subsequently explored through integrative downstream analyses. Methods and findings DEGs were identified using DESeq2 and further analyzed for functional enrichment (ClusterProfiler, Pathview, and GSEA), co-expression gene networks, and tumor immune infiltrate deconvolution (CIBERSORTx). The GSE119810 dataset was used for exploratory overall survival (OS) analysis. Transcriptomic data from 88 CMC cases and adjacent healthy mammary tissue samples identified eight DEGs common across all four datasets. Among these, ACAN , COL11A1 , EDIL3 , NDUFA4L2 , and IGFBP5 showed higher transcript levels in CMC tissues than in healthy mammary tissue, whereas TNNC1 , PCK1 , and METTL24 showed lower transcript levels in CMC tissues than in healthy mammary tissue. Functional enrichment analyses indicated that DEGs with higher transcript levels in CMC were predominantly associated with extracellular matrix remodeling, cell adhesion, tumor microenvironment interactions, immune and inflammatory responses, and signaling pathways involved in tumor progression and metastasis. In contrast, DEGs with lower transcript levels were mainly enriched for cytoskeletal organization and tissue structural integrity, suggesting a loss of normal mammary gland architecture and myoepithelial-associated functions during tumor progression. GSEA further demonstrated coordinated enrichment of hallmark gene sets related to cell-cycle dysregulation, proliferation, epithelial–mesenchymal transition, metabolic adaptation, inflammatory signaling, and stromal remodeling, supporting the presence of integrated transcriptional programs that drive tumor progression and TME remodeling in CMC. Co-expression gene network analysis revealed a highly modular organization, with densely interconnected clusters of co-expressed genes that may reflect coordinated biological processes and regulatory programs. Exploratory CIBERSORTx analysis found no significant differences in the relative proportions of the 22 infiltrating immune cell types between CMCs and paired healthy controls after multiple-comparison corrections. Nevertheless, dataset-specific trends were observed in regulatory T cells, M1 macrophages, activated CD4 memory T cells, plasma cells, dendritic cells, and mast cells, though these findings should be interpreted cautiously. An exploratory survival analysis of 1,759 DEGs from the GSE119810 dataset identified 53 genes nominally associated with overall survival in CMC. However, none remained statistically significant after multiple-testing correction, underscoring the exploratory nature of these findings and the need for validation in larger cohorts. Conclusion This study provides a preliminary transcriptomic framework for CMC, identifying candidate genes and pathways associated with tumor-related processes and supporting future functional validation to clarify their roles in tumorigenesis, progression, and tumor aggressiveness. However, these findings remain exploratory and require validation in larger cohorts to confirm their diagnostic and prognostic relevance, given the limitations of secondary data analyses and potential variability in tissue collection and processing across studies.

Comparative effects of SGLT2 inhibitors and GLP-1 receptor agonists on osteoarthritis risk in patients with type 2 diabetes mellitus: A multi-institutional cohort study

Objectives Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated metabolic and anti-inflammatory benefits, which may influence the risk of osteoarthritis (OA) in patients with type 2 diabetes mellitus (T2DM). However, their comparative impact on OA incidence remains unclear. This study aimed to evaluate and compare the effects of SGLT2 inhibitors and GLP-1 RAs on the risk of developing OA in patients with T2DM. Methods A retrospective cohort study was conducted using the TriNetX database, including adults with T2DM who were newly prescribed either SGLT2 inhibitors or GLP-1 RAs between January 2017 and December 2019. After propensity-score matching, 452,445 patients were included in each group. The primary outcome was OA incidence over five years. Secondary outcomes included knee OA, hip OA, total knee arthroplasty (TKA), total hip arthroplasty (THA), and major joint injections. Results The SGLT2 inhibitor group had a significantly lower risk of OA compared with the GLP-1 RAs group (HR, 0.921; 95% CI, 0.895–0.946), with a greater reduction observed for knee OA (HR, 0.831; 95% CI, 0.783–0.882). No significant differences were observed in THA or TKA risk. SGLT2 inhibitor users also had fewer major joint injections (HR, 0.915; 95% CI, 0.882–0.951). Conclusions Among patients with T2DM, SGLT2 inhibitors were associated with a lower risk of OA, particularly knee OA and joint injections, compared to GLP-1 RAs. These findings support further investigation into the potential association between SGLT2 inhibitor use and lower OA-related outcomes.

Multi-spatial resolution hyperspectral image change detection network integrating feature difference structure

Change detection (CD) can detect changes in the earth’s surface. However, the existing Siamese network-based CD methods usually calculate the Euclidean distance (ED) between two branches to obtain difference features, ignoring the deeper feature disparities captured by the CNN. In addition, the patch obtained in the CD method using spatial information may have the phenomenon that the adjacent pixels and the pixels to be classified are not the same object or change type. To deal with the aforementioned challenges, we propose FDS-BINet, a multi-spatial resolution network integrating a Feature Difference Structure (FDS) and Bicubic Interpolation (BI). The FDS module progressively extracts deep pixel-level differences through residual-enhanced Siamese branches, while BI interpolates the absolute distance spectrum to recover subpixel-level changes. The main contributions of this article are as follows: 1) A change detection framework called FDS-BINet has been proposed that fuses pixel-level and subpixel-level change information. 2) A feature difference structure (FDS) is designed to obtain deep difference features of pixel-level spatial information of bitemporal HSIs; 3) The bicubic interpolation (BI) algorithm is used for absolute distance (AD) spectrum interpolation. We can effectively boost the spatial resolution of AD spectrum data, enabling us to extract feature differences at the subpixel level from bitemporal hyperspectral images (HSIs). The experimental results demonstrate that the proposed FDS-BINet has better performance compared with representative methods in the field of HSI CD.

Textual overlap rather than domain alignment: A comparative study of fine-tuning strategies for specialised machine translation with large language models

General-purpose large language models (LLMs) may struggle in specialised machine translation, but the conditions under which fine-tuning improves translation performance remain unclear. This study compares full-parameter fine-tuning (FPFT) and parameter-efficient fine-tuning (PEFT) for Chinese-English political discourse translation using a purpose-built corpus and the Qwen3-14B model. Translation performance was assessed on three 50-item test sets using BLEU, ROUGE-L F1, METEOR, and BERTScore F1, together with BLEU pass-rate likelihood-ratio G 2 tests, paired t-tests, and paired Cohen’s d z for item-level score differences. The results reveal a clear contrast between unseen in-domain evaluation, maximum-overlap benchmarking, and semantically related but non-fine-tuned evaluation. On Test Set A and Test Set C, neither fine-tuning strategy produced a statistically significant BLEU pass-rate advantage over the base model, and paired tests across the continuous metrics did not show consistent fine-tuning gains. On Test Set B, which was sampled from the fine-tuning corpus, both fine-tuned models substantially outperformed the base model across all four metrics, with FPFT achieving the highest scores and PEFT providing a more computationally efficient alternative. These findings indicate that textual overlap between training and deployment data, rather than broad domain similarity alone, strongly conditions the observed benefit of fine-tuning. The study offers an empirically grounded framework for selecting fine-tuning strategies in specialised machine translation.

Pre-transplant dialysis vintage and post-transplant outcomes: A retrospective cohort study in Korean kidney transplant recipients

Background Kidney transplantation (KT) is the preferred treatment for end-stage renal disease (ESRD) due to its advantages over dialysis. Although the benefits of preemptive KT are well established, the association between pre-transplant dialysis duration and post-transplant outcomes remains uncertain. Objective To evaluate the association between pre-transplant dialysis vintage and post-transplant outcomes in Korean KT recipients using real-world data from a tertiary transplant center. Methods We retrospectively evaluated 1,843 first KT recipients transplanted between 2006–2021. Dialysis duration was used as a categorical variable divided by tertiles according to distribution of time of analysis, and preemptive transplantation was categorized as a separate group. Primary outcomes included death-censored graft loss, all-cause mortality and composite outcomes. Survival was assessed using Kaplan–Meier and Cox proportional hazards models at a 95% confidence level. A deceased-donor KT (DDKT) subgroup analysis was also performed. Results 369 patients underwent preemptive KT, and 1,474 dialysis-exposed recipients were categorized into tertile 1 (n = 492), tertile 2 (n = 491), and tertile 3 (n = 491), with mean pre-transplant dialysis durations of 1.2, 21.4, and 107.6 months, respectively. Compared with preemptive KT, all-cause mortality did not differ in the first or second tertiles but was significantly higher in the third tertile (aHR 3.55; 95% CI 1.43–8.81; p  = 0.006). In the overall cohort, the third tertile was also associated with higher risks of death-censored graft failure and the composite outcome. However, in the deceased-donor KT subgroup, death-censored graft failure did not differ significantly across tertiles, and the composite outcome did not show a monotonic dose-response pattern. Conclusions Prolonged pre-transplant dialysis was associated with a higher risk of all-cause mortality, whereas its association with graft failure was less consistent, particularly among deceased-donor KT recipients.

Comparative proteomics and metabolomics reveals distinct host protein quality control and metabolic signatures during recombinant IL1-His and IL15-His expression in Nicotiana benthamiana

Agrobacterium-mediated transient expression in Nicotiana benthamiana is widely used for recombinant biopharmaceutical production. To investigate the host plant response upon human cytokine production with contrast accumulation, we expressed codon optimized human IL1 beta, serving as a high expression benchmark with a yield of approximately 80 μg/g leaf fresh weight, and IL15 with undetected signal on western blot, representing protein with low level of accumulation, using the geminiviral vector system. A combined proteomics and metabolomics technique was applied to elucidate underlying cellular mechanisms. Quantitative proteomics revealed that IL1-His was robustly detected (9 unique peptides, 83% coverage), whereas no IL15-His–derived peptides were identified. Based on pathway analysis, the expression of IL15-His induced chaperone expression, with downregulation of photosynthetic and primary metabolism pathways. Additionally, metabolomic pathway analysis revealed that IL1-His preferentially drives the branched chain amino acid biosynthesis, but IL15-His shifts metabolism towards phenylpropanoid biosynthesis routes. These findings underscore that the characteristics of the target protein and its interaction with the host's physiology could influence the yield of the recombinant protein production in plants.

Population structure and diversity of common bean (Phaseolus vulgaris L.) landraces in the Peruvian Amazon

Common bean ( Phaseolus vulgaris L.) is a globally important grain legume, yet the genetic diversity of landraces from the Peruvian Amazon remains poorly characterized. This study aimed to assess the population structure and genetic diversity of Amazonian common bean by integrating morphological and genome-wide SNP data. A total of 476 accessions were phenotyped using 18 morphological traits, and 647 accessions were genotyped with 23,050 high-quality DArTseq SNP markers. Cluster and population structure analyses consistently identified two major genetic groups corresponding to the Andean (n = 284) and Mesoamerican (n = 363) gene pools, with further subdivision into four subgroups at K = 4. Principal Coordinate Analysis supported this structure, with the first axis explaining 62.62% of the variation in the molecular data. Genetic diversity was high, with 94.9% of SNPs successfully mapped and more than 94% of loci polymorphic in both groups. However, observed heterozygosity was low (Ho = 0.035–0.041) compared to expected heterozygosity (He ≈ 0.147–0.148), and inbreeding coefficients were high (FIS = 0.52–0.54), consistent with the predominantly self-pollinating mating system. Hill number analyses indicated similar allelic richness between groups (q = 0: α ≈ 1.95–1.97) and low differentiation in allele presence (β = 1.04), whereas differentiation increased when allele frequencies were considered (q = 2: β ≈ 1.4–1.5). Morphological analyses revealed substantial phenotypic variation, including flowering time (32–75 days), pod length (6.5–17.3 cm), and number of locules per pod (2–11), and identified four distinct phenotypic clusters. No redundant accessions were detected. These results indicate that Amazonian landraces harbor high levels of genetic and phenotypic diversity structured by gene pool origin and local adaptation. The integration of morphological and SNP data provides a robust framework for germplasm characterization and highlights the importance of conserving these genetic resources for future breeding and sustainable agriculture.

Incidence and risk factors for recurrent IgA nephropathy after kidney transplantation: A multicenter cohort study from Denmark

Background Recurrent immunoglobulin A nephropathy after kidney transplantation remains a major clinical challenge, but risk factors are not fully defined. This study aimed to evaluate the incidence of biopsy-proven recurrent IgAN and identify risk factors for recurrence in a contemporary Scandinavian cohort. Methods We conducted a multicenter cohort study including adult patients with biopsy-proven immunoglobulin A nephropathy who received a first kidney-only transplantation between 1990 and 2020 across two Danish transplantation centers. Recurrence incidence and associations with clinical and donor-related characteristics were assessed during follow-up. Results A total of 118 recipients were followed for a median of 5.5 years. Biopsy-confirmed recurrence occurred in 14% of patients, corresponding to a cumulative incidence of 16% at 10 years post-transplantation. Younger age at immunoglobulin A nephropathy diagnosis, faster progression to kidney failure, and receipt of a kidney from a living or genetically related donor were independently associated with an increased risk of recurrence. Maintenance post-transplant steroid use was not associated with recurrence. Recurrent immunoglobulin A nephropathy was associated with an increased risk of graft failure compared with non-recurrent disease (unadjusted HR 3.8; adjusted HR 6.7). Conclusions Recurrence of IgAN after kidney transplantation remains a clinically significant challenge, associated with younger age, rapid progression to KF, and transplantation from living or genetically related donors. Maintenance post-transplant steroid use was not associated with recurrence risk in this cohort. Larger and more diverse cohorts are warranted to clarify donor-related risk, strengthen the evidence on immunosuppressive protocols and guide strategies to improve graft outcomes.