Not available.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age, typically diagnosed through a combination of clinical evaluation, laboratory testing, and ultrasonography. However, this multimodal diagnostic pathway is often time-consuming, costly, and dependent on resource availability, thereby limiting its accessibility in real-world clinical settings.

In this study, we propose AutoPCOS, a stepwise multimodal intelligent framework for flexible PCOS risk stratification and diagnostic support. Using a publicly available Kaggle PCOS dataset, features were categorized into three modalities: clinical, laboratory, and ultrasound data. Based on data availability, four predictive models were constructed: (1) clinical-only, (2) clinical + laboratory, (3) clinical + ultrasound, and (4) full multimodal models. Random Forest was employed as the primary classifier, with comparisons against Logistic Regression, Support Vector Machine, Decision Tree, and Gradient Boosting. Subgroup analyses were conducted based on body mass index (BMI) and menstrual cycle patterns.

The proposed framework demonstrated robust predictive performance across different data availability scenarios. Notably, the models achieved strong performance in subgroups with BMI < 24 and irregular menstrual cycles, with precision values reaching ≥ 0.929. Comparative analysis confirmed the effectiveness of the Random Forest model. Furthermore, the integration of a knowledge base and the Lingshu large language model enabled interpretable risk explanations and personalized recommendations.

AutoPCOS provides a flexible and resource-aware framework for PCOS risk assessment that adapts to varying clinical conditions and data accessibility. By supporting stepwise decision-making and enhancing interpretability, the system shows potential as a practical tool for both patients and healthcare providers. Future work will focus on validation using real-world clinical datasets and improving model generalizability.

This study systematically reviews the current application of digital health interventions in cancer patients, clarifies their implementation characteristics and intervention effects in managing economic toxicity, and provides a reference for intervention programs to reduce the economic toxicity of patients.

Relevant studies were systematically retrieved from PubMed, Web of Science, Cochrane Library, Embase, CINAHL, CNKI, CBM, WanFang Database, and VIP Database from their inception to February 6, 2026. Data from the included literature were extracted and analyzed.

A total of 22 studies were included. Digital health technologies are applicable to multiple stages of cancer patient diagnosis, treatment, and rehabilitation. Among these, remote financial navigation or consultation is the most commonly used intervention method. Existing research has shown positive results in improving cost communication skills, facilitating financial assistance, and enhancing intervention feasibility, but evidence regarding improvements in economic toxicity scales and the alleviation of long-term financial difficulties exhibits some heterogeneity.

Digital health technologies, with their high accessibility, scalability, and ease of remote access and follow-up, offer unique advantages in managing the economic toxicity of cancer patients. Current research in this field has gradually shifted from single-stage interventions to comprehensive intervention pathways. Future research should focus on the dynamic evolution of economic toxicity at different stages of diagnosis and treatment, promote the standardization of intervention procedures and outcome evaluations, and develop personalized digital intervention strategies to mitigate the economic toxicity of cancer patients.

https://doi.org/10.17605/OSF.IO/4DYN3.

Persistent infections with human papillomavirus (HPV) cause approximately 95% of cervical cancers. The introduction of cytology screening has, however, significantly reduced morbidity and mortality rates. More recently, HPV DNA testing has been shown to be more sensitive than traditional cytology-based testing in detecting cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+). Self-sampling for HPV testing offers a viable alternative to clinician-performed sampling and could potentially increase participation rates in organized screening programs. Here, we compared the accuracy of self-collected vaginal samples with clinical-collected cervical samples for HPV-based screening and evaluated the acceptability of HPV self-sampling among Polish women.

Women with unclear or abnormal results at their last cytology screening were invited to participate. Each participant submitted two swabs for HPV testing: one clinical-collected cervical swab and one self-collected vaginal swab (Evalyn^® Brush). Both sample types were subsequently tested with the EUROArray HPV assay. Participants also completed a questionnaire to assess their experiences with the self-sampling procedure and express their opinions on it.

In total, 180 women aged 30 to 70 years were recruited. The prevalence of high-risk (hr) HPV was 56.7% in clinician-collected samples and 55.0% in self-collected samples. Overall concordance for any HPV, hr-HPV and low-risk (lr) HPV detection between self-collected and clinician-collected samples was 88.9%, 86.1%, and 85.0%, respectively. Most participants found self-sampling comfortable (82.4%), useful (87.0%), and convenient (85.8%) and felt low/very low stress (58.0%) while sampling. In total, 81.3% of the women reported that it was practically painless and 77.2% felt less embarrassed. Of the respondents, 51.1% preferred clinician-collected sampling, 40.9% preferred self-sampling, while 4.6% had no preference.

Vaginal self-sampling using the Evalyn^® Brush showed substantial agreement with cervical clinician-sampling for HPV detection using the EUROArray HPV test. Self-sampling for HPV testing was well-accepted by the participants. It represents a feasible alternative for clinical sampling in Poland, which could be effectively integrated into the national HPV screening program.

Neutrophil extracellular traps (NETs) serve a dual role in tumor progression. On the one hand, they promote tumor invasion and metastasis by facilitating cancer cell adhesion to the endothelium, supporting vascular remodeling and establishing pre-metastatic niches. On the other hand, NETs exert potent immunosuppressive effects that foster tumor immune evasion and contribute to immunotherapy resistance. Specifically, NETs create physical barriers within the tumor microenvironment, directly suppress effector immune cells, and degrade critical molecules such as interferon-γ, leading to immune exhaustion and dysfunction. The present review comprehensively summarizes the biology of NETs and their molecular mechanisms in tumor metastasis, with a particular focus on NET-mediated immunosuppression and its causal link to immunotherapy resistance. This review further discusses emerging strategies that disrupt NET formation or function, which may reverse their immunosuppressive impact and restore antitumor immunity, thereby enhancing the efficacy of current immunotherapies.

Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1 (DRAK1/STK17A) is a serine/threonine kinase of the Death Associated Protein Kinase (DAPK) family. STK17A is widely expressed and enriched in immune tissues, and is primarily localized in the nucleus, though it can translocate to the cytoplasm in response to specific stimuli. STK17A stimulates apoptosis and cytoskeletal dynamics, but its physiological roles remain incompletely defined, in part due to limited availability of potent/selective chemical probes and the absence of STK17A in commonly used rodent models. In this review, we summarize current knowledge on STK17A, including its structure, evolution, expression patterns, molecular interactions, and roles in cancer as well as in autoimmune, cardiovascular, infectious, and neurological disorders. We also compare STK17A with its closest homolog, STK17B, highlighting both shared features and functional distinctions. The review further examines recent medicinal chemistry efforts that have yielded the first small-molecule modulators of STK17A (DRAK1) and STK17B (DRAK2), including dual inhibitors and emerging selective scaffolds. These compounds can serve as valuable chemical probes and hold promising therapeutic potential. Nonetheless, challenges of selectivity and functional validation remain, emphasizing the need for continued medicinal chemistry efforts to unlock the full potential of STK17A as a therapeutic target across cancer, autoimmune, and neurodegenerative diseases.

Sonodynamic therapy (SDT) has emerged as a promising modality for treating deep-seated tumors. It has been demonstrated that SDT effectively induces immunogenic cell death (ICD), thereby initiating a systemic anti-tumor immune response - a process known as sonodynamic immunotherapy. However, its efficacy is severely limited by the hypoxic tumor microenvironment (TME) and elevated glutathione (GSH) levels, which together scavenge reactive oxygen species (ROS) and create a potent antioxidant barrier.

Ultra-small Mn₃O₄ nanoparticles with multi-enzyme mimicking activity were synthesized, and co-encapsulated with the sound sensitizer Ag₂S quantum dot (Ag₂S QD) in cell membrane hybrid liposomes to construct a biomimetic nanoplatform (Mn₃O₄/QD@LM). The Catalase and glutathione peroxidase activities of Mn₃O₄/QD@LM were evaluated. Its antitumor efficacy in vitro was evaluated by measuring ROS levels, mitochondrial membrane potential staining, live/dead cell staining, and apoptosis analysis. By recording tumor growth and performing histological and immunohistochemical examinations, its antitumor effects in vivo were investigated in a mouse model of colon cancer. Flow cytometry analysis was used to analyze the tumor immune microenvironment.

Mn₃O₄/QD@LM functioned as a "ROS amplifier" by exhibiting catalase-like and glutathione peroxidase-like activities, which alleviated tumor hypoxia and depleted GSH, thereby markedly enhancing SDT efficacy. Moreover, released Mn²⁺ ions generated highly cytotoxic hydroxyl radicals via a Fenton-like reaction, further augmenting tumor cell killing. In vitro experiments confirmed that Mn₃O₄/QD@LM effectively induced ICD and activated the STING pathway. Benefiting from homologous targeting, the nanoplatform achieved efficient accumulation in tumor tissue in vivo. Upon ultrasound activation, Mn₃O₄/QD@LM significantly inhibited tumor growth both in vitro and in vivo. Notably, it remodeled the tumor immune microenvironment by promoting CD8⁺ T cell infiltration, enhancing the secretion of IFN-γ and TNF-α, and reducing the populations of regulatory T cells and myeloid-derived suppressor cells.

Mn₃O₄/QD@LM confirms the synergistic role of multi-enzyme activities and STING pathway activation in potentiating sonodynamic immunotherapy, and provides an innovative strategy to overcome TME-mediated therapy resistance.

Imaging with prostate-specific membrane antigen (PSMA) PET has significantly improved prostate cancer staging with superior diagnostic performance compared to conventional methods. Although it is increasingly adopted in clinical practice, several barriers hinder its full integration into routine workflows. This review highlights the existing knowledge gaps, infrastructure limitations, and inconsistencies in interpretation that affect the utility of PSMA PET across healthcare settings. We examine the potential reasons behind variability in scan performance, including scanner design, detector technology, sensitivity, and resolution, as well as the accreditation status of the facilities and reader expertise. We also highlight the inconsistent understanding of PSMA PET ordering practices, particularly among urologists, and the influence of ownership-driven utilization, both of which contribute to underuse and overuse. Radiology reporting that lacks sufficient detail and a shortage of trained nuclear medicine specialists may present additional challenges to effective treatment planning, although diagnostic radiologists also contribute to PET scan interpretation. This review highlights the potential role of standardized reporting protocols, accreditation, expanded education, and integration of AI tools in enhancing diagnostic accuracy and consistency. Additionally, we examine the impact of PSMA PET on clinical decision-making in unfavorable intermediate-, high risk-, and biochemically recurrent prostate cancer, as well as the emerging role of PSMA PET-derived metrics in staging, biopsy guidance, and treatment planning. While PSMA PET has shown value in modifying management strategies, its clinical benefit requires validation through future, prospective, outcome-driven studies. In addition, emerging applications of PSMA PET in non-prostate malignancies hold the potential to transform diagnostic and therapeutic approaches beyond prostate cancer.

Combining targeted alpha and beta therapy may address challenges such as toxicity, treatment resistance, and tumor heterogeneity. We evaluated the feasibility and therapeutic effectiveness of a DOTA-PRIT approach using a ¹⁷⁷Lu/²²⁵Ac radioisotope cocktail, directly compared with monotherapies targeting GPA33 in human colorectal cancer (CRC) xenografts in mice.

A three-step pretargeting regimen was employed: an anti-GPA33/anti-DOTA bispecific antibody (BsAb), a dendrimeric clearing agent, and radioligands labeled with ¹⁷⁷Lu, ²²⁵Ac, alone or in combination. Serial biodistribution studies in GPA33(+) SW1222 xenografts evaluated how co-injection of ¹⁷⁷Lu and ²²⁵Ac radioligands affected tumor uptake and biodistribution. iQID digital autoradiography was used to visualize isotope distribution in tumor and kidney samples. Mice bearing SW1222 and LS174T xenografts received mono- or combination-therapy regimens delivering 37-38 Gy to tumors. Dose-escalation studies, histopathology, and qPCR analysis of DNA-damage and apoptosis-related genes were also performed.

Biodistribution and autoradiography confirmed that the ¹⁷⁷Lu- and ²²⁵Ac-labeled ligand effectively bound to pretargeted GPA33(+) xenografts when co-administered. High therapeutic indices were maintained across treatment groups, with autoradiography showing general overlap of co-injected probes. Combination therapy demonstrated comparable efficacy to monotherapies. At 150 d post-treatment, no treatment group had reached median survival; 5/9 mice receiving the cocktail (62.9 MBq ¹⁷⁷Lu + 18.5 kBq ²²⁵Ac) were alive, including two tumor-free. In comparison, 4/8 mice in the ¹⁷⁷Lu group and 8/10 in the ²²⁵Ac group survived, with 3 and 5 tumor-free animals, respectively. Combination therapy was well tolerated, showing no significant adverse effects on body weight or blood cell counts compared to healthy controls. Combined administration was safe up to 62.9 MBq ¹⁷⁷Lu + 37 kBq ²²⁵Ac, resulting in 10/10 histological cures.

Our findings confirm the feasibility of a combined ¹⁷⁷Lu and ²²⁵Ac DOTA-PRIT in mice with established SW1222 xenografts, demonstrating tolerability and effectiveness comparable to monotherapy at equivalent average absorbed tumor doses.

Proteolysis-targeting chimeras (PROTACs) represent a powerful therapeutic modality for selective protein degradation but often suffer from poor pharmacokinetics and limited tumor-targeting. To overcome these constraints, we developed albumin-binding BRD4-degrading PROTACs (Alb-TACs) with esterase-cleavable maleimide linkers that hitchhike endogenous albumin and enable esterase-responsive BRD4 degradation in tumors.

Alb-TACs were synthesized by conjugating two esterase-cleavable maleimide linkers, bicyclononyne-polyethylene glycol-maleimide (BCN-PEG₂-Mal) or N-(2-aminoethyl)maleimide (AE-Mal), to BRD4-degrading PROTAC (ARV-771), resulting in Alb-TAC#1 and Alb-TAC#2, with distinct albumin- and esterase-binding properties. To select effective Alb-TAC, the binding ability to albumin and esterase-specific cleavage of Alb-TACs were carefully assayed using MALDI-TOF, PAGE, and time-course HPLC. Furthermore, the tumor-targeting efficacy of Alb-TACs was assessed by fluorescence imaging in CT26 tumor-bearing BALB/c mice. Next, we investigated the BRD4 degrading efficiency of Alb-TAC in a cell culture system and in CT26 tumor-bearing mice. Finally, the immunogenic cell death (ICD) and reprogrammed immune cells of Alb-TAC-treated tumors were carefully characterized.

Alb-TAC#2 containing the AE-Mal linker exhibited rapid albumin binding, accelerated esterase-responsive activation, and enhanced tumor accumulation compared to ARV-771 and Alb-TAC#1 due to its flexible chemical structure. In the CT26 cell culture system, Alb-TAC#2 efficiently degraded BRD4, resulting in BRD4-deficient cell death. Furthermore, in CT26 tumor-bearing mice, Alb-TAC#2 achieved extensive apoptosis through robust BRD4 degradation, leading to marked downregulation of c-Myc, Bcl-2, and PD-L1. Moreover, Alb-TAC#2 induced hallmarks of ICD (elevated surface CRT, extracellular ATP, and HMGB1) and reprogrammed the tumor microenvironment by enhancing CD8⁺ T cell infiltration, promoting dendritic cell maturation, and reducing regulatory T cell function.

This esterase-responsive albumin-binding PROTAC design could overcome pharmacokinetic barriers of conventional BRD4-targeting PROTACs by enhancing tumor-specific delivery and esterase-responsive BRD4 degradation in solid tumors. In summary, esterase-responsive albumin-binding PROTAC is proven as a promising strategy that effectively modulates the pharmacokinetics and therapeutic performance of PROTACs for cancer immunotherapy.