The article explores the shift from Asimov's laws, centered on machine obedience, to Kasparov's laws of "hybrid intelligence". While Asimov focused on preventing harm through autonomous constraints, Kasparov emphasizes that the best performance arises from the optimal orchestration of human, machine, and process. This perspective suggests that a "weak human + machine + superior process" can outperform a "strong human + machine + inferior process". Empirical studies in radiology are consistent with this socio-technical conjecture. Studies in radiology indicate that specific collaboration protocols allow human-AI teams to surpass isolated models. Notably, research confirms that less proficient clinicians embedded in effective protocols can achieve higher accuracy than clinicians with higher baseline accuracy operating under less effective protocols. This framework views AI as a component of "superminds" - collective cognitive architectures that enhance plural decision-making. Ultimately, the value of AI is an emergent property of the organizational system. Rather than focusing solely on model accuracy, designers must create interaction protocols that calibrate trust and prevent professional deskilling. The goal is to move toward a synergy where machines help human collectives become more intelligent.
Treatment of opioid use disorder (OUD) with buprenorphine reduces overdose and all-cause mortality, yet access and retention remain limited. Much of the literature describing barriers to buprenorphine access and retention has focused on practitioner-level or patient-level barriers, but less is known about how potential policy and payment levers may influence prescribing behaviors and treatment practices from the practitioner perspective. To explore perspectives among OUD treatment program clinicians and staff about how broader policy and payment structures influence adoption of buprenorphine treatment and low-barrier care practices that promote access and retention. In this qualitative study, semistructured interviews were conducted from December 2022 to July 2023. Participants included clinicians and staff from a range of outpatient treatment programs providing buprenorphine in Philadelphia, Pennsylvania. Interviews examined prescribing practices and the influence of policy, payment structures, and regulatory requirements on clinical care. Transcripts were analyzed using thematic content analysis. A total of 28 practitioners and staff (13 men [46%]; 11 [39%] aged 41-50 years), including medical clinicians, therapists, and other administrative staff, were interviewed. Participants included 17 physicians (61%), 7 therapists (25%), 1 advanced practice practitioner (4%), 1 administrator (4%), and 2 other staff (8%). Twenty-four participants (86%) had at least 5 years of experience treating OUD, and all clinicians had obtained a DATA-2000 waiver, also called an X-waiver, to prescribe buprenorphine. Participants viewed the X-waiver as a symbolic barrier, but identified policy factors like insurance coverage, reimbursement rates, payer policies, and licensure requirements as key variables influencing clinical practice. Clinics relied on supplemental funding to sustain care for uninsured patients. Participants reported that payer-imposed requirements, such as prior authorizations and rigid attendance-based reimbursement, undermined timely access and individualized care and that regulatory frameworks often conflicted with harm reduction principles and created staffing and documentation burdens. This qualitative study of clinicians and staff in buprenorphine treatment programs found that broader policy and payment reforms could help support low-barrier buprenorphine treatment. Enhancing reimbursement, reducing administrative burdens, and aligning licensure and payer policies with evidence-based practices may improve access and retention. These findings offer actionable insights for policymakers, payers, and health systems seeking to address persistent gaps in OUD treatment.
Vestibular schwannomas (VS) present a clinical challenge in management decision-making due to their difficult-to-access location, unpredictable growth, and potential impact on crucial neurological function. This systematic review evaluates and summarizes the potential for radiomics, a computational tool that extracts quantitative features from imaging, to predict VS clinical outcomes and assess treatment responsiveness. Studies were extracted by searching PubMed, OVID Medline, and Web of Science databases. Included studies analyzed radiomic features from MRI as independent variables and varied in their methodology to predict clinical outcomes. Studies evaluated associations between radiomic features, pre-procedural clinical features, and post-procedural outcomes. Thirteen retrospective studies met inclusion criteria; eleven of these used machine learning models to analyze radiomic MRI features. One non-ML study correlated longitudinal tumor volumetric changes with texture features. All segmentation workflows utilized manual or semi-automated approaches to determine the lesion's region of interest. Models based on pre-procedural imaging demonstrated moderate predictive accuracy by Area Under the Receiver Operating Characteristic curve (AUC = 0.66-0.7), while post-procedural models showed moderate to strong predictive capacity (AUC = 0.75-1.0). One study employed a convolutional neural network evaluating postoperative facial nerve outcomes (AUC = 0.89) that outperformed traditional ML models (AUC = 0.64-0.85). Radiomics-based predictive modeling in VS shows encouraging preliminary results across a range of clinical outcomes. However, small sample sizes, retrospective designs, and lack of standardization and external validation in models hinder its widespread applicability. Addressing these limitations through prospective studies with standardized datasets and models, potentially incorporating deep learning, will be essential to improve generalizability and support clinical integration.
To evaluate the effectiveness and cost-effectiveness of pembrolizumab combined with chemotherapy and anti-angiogenesis treatment for PD-L1 CPS 1-10 cervical cancer (CC) patients from the perspective of US healthcare payers. KM curves for the CPS 1-10 subgroup were derived using the KMSubtraction workflow to reconstruct individual patient data, with analysis based on restricted mean survival time. A partitioned survival model (PFS, PD, death) was used for cost-effectiveness analysis, applying a $150,000 per QALY willingness-to-pay threshold. Pembrolizumab plus chemotherapy significantly improved PFS (RMST difference 5.06 months) and OS (RMST difference 5.84 months) versus placebo. The treatment increased QALYs by 1.17 at an additional cost of $297,505,yielding an ICER of 254,262 $/QALY. A threshold analysis indicated that an effective pembrolizumab price of $25.80 per mg would be required for the regimen to meet the $150,000/QALY threshold. Sensitivity analysis identified drug prices, health state utilities, and discount rates as key influencing factors. Pembrolizumab+chemotherapy significantly improved PFS and OS in PD-L1 CPS 1-10 CC patients, with higher mean RMST than the placebo group. However, it is not cost-effective at current prices, but reducing pembrolizumab's price could improve its cost-effectiveness.
This commentary evaluates a propensity-matched study by Nakamura et al. comparing robotic-assisted (RATS) versus video-assisted complex segmentectomy. The original study demonstrated that despite longer operative times, RATS achieved comparable perioperative outcomes with significantly fewer postoperative arrhythmias. While methodologically robust, limitations include the retrospective design, the absence of long-term oncologic data, and a lack of cost-effectiveness analysis. Furthermore, the potential influence of surgeon proficiency on outcomes was not assessed. Future multicenter prospective registries with comprehensive outcome measures are needed to validate these findings.
Glioblastoma multiforme (GBM) remains an aggressive brain malignancy with dismal prognosis despite current standard-of-care therapies. The gastrin-releasing peptide receptor (GRPR) is overexpressed in gliomas and represents a potential therapeutic target. However, systemic radionuclide delivery is limited by poor tumor penetration and off-target toxicity. GRPR expression and prognostic relevance were analyzed using Chinese Glioma Genome Atlas and a clinical-trial dataset, respectively at the transcriptomic and protein levels. [177Lu]Lu-RM26, a lutetium-177-labeled GRPR-targeting antagonist, was evaluated in vitro, and administered intratumorally via convection-enhanced delivery in an orthotopic GL261Fluc+ glioblastoma model. Pharmacokinetic characteristics, including tumor retention and biodistribution, were evaluated by serial single-photon emission computed tomography and gamma-counting. Efficacy was assessed by tumor volume, bioluminescence signal, and overall survival. Safety was evaluated through body weight monitoring, neurological scoring, rotarod testing, hematology, and immunohistochemical staining. Mechanistic insights were obtained via bulk RNA-sequencing and Western blotting. Higher GRPR expression correlated with poorer-prognosis glioma subtypes and reduced survival. In vitro assays showed dose-dependent inhibition of GL261Fluc+ cell viability, proliferation, and invasion. Locoregional [177Lu]Lu-RM26 administration led to prolonged tumor retention (74.7 h), high absorbed dose (2.71 × 106 mGy·MBq- 1), and minimal off-target uptake. Treated mice exhibited marked tumor growth inhibition, reduced bioluminescence signal, and extended survival compared to controls. No significant short-term systemic toxicity or neurological impairment was observed. Transcriptome and Western blotting findings were consistent with DNA replication stalling and G2/M arrest. Locoregional [177Lu]Lu-RM26 therapy enables sustained, tumor-specific β-radiation with minimal systemic exposure, representing a promising locoregional strategy for GRPR-positive GBM.
To evaluate the short- and mid-term volume reduction rate(VRR) after percutaneous ethanol injection(PEI), at 1,3 and 6 months, in patients with cystic or predominantly cystic thyroid nodules(CNs/pCNs, respectively), conducting a systematic review and meta-analysis of published data on VRR outcomes across these intervals. A systematic search of articles published up to October 30,2025 identified studies reporting PEI treatment for CNs/pCNs.Characteristics of the study design, CNs/pCNs cohorts, and outcomes of interest(VRR at 1,3 and 6 months of follow up)were extracted.Statistical analysis included a random-effects meta-analysis, assessment of heterogeneity with use of the I2 statistic, and meta-regression and subgroup analyses to explore potential sources of heterogeneity. Six studies comprising 431 CNs/pCNs were included.The pooled VRRs at 1,3 and 6 months post-PEI were 85.18%(95% CI: 80.72-89.64),91.50%(95% CI: 88.88-94.12) and 93.11%(95% CI: 90.91-95.31),respectively. Stratifying by nodule cystic composition, the VRR at consecutive follow-up time points was significantly different between the 1- and 3-month intervals in both subgroups [CN: VRRs at 1, 3 and 6 months were 91.16% (88.38-93.93), 95.69% (94.16-97.22) and 96.02% (94.16-97.87), respectively; pCN: VRRs at 1,3 and 6 months were respectively 80.19% (77.04-83.33), 87.08% (84.95-89.2) and 90.01%(88.83-91.19)].A secondary meta-regression analysis with baseline mean volume as covariate demonstrated a significant inverse association with VRR at 1 and 3 months in pCN(p = 0.02). By providing pooled VRRs for the short- and mid-term follow-up, this meta-analysis should be regarded as an initial step, paving the way for larger, high-quality studies aimed at standardizing the PEI procedure and supporting its incorporation into future dedicated guidelines.
Helicobacter pylori (H. pylori) is a globally prevalent gastric pathogen whose increasing antimicrobial resistance has reduced the efficacy of conventional eradication regimens. Bacteriophages and phage-derived products have therefore attracted growing interest as alternative antimicrobial strategies against H. pylori. However, progress in this field remains constrained by the limited availability of cultivated phages, the underexplored reservoir of prophages and uncultivated phages, narrow host range, and poor stability under gastric conditions. In this review, we summarize the current landscape of H. pylori phage research, including both virulent and temperate phages, and discuss how genome-based mining is expanding access to previously inaccessible phage resources. We further examine recent application-oriented advances, including artificial intelligence-assisted endolysin discovery, receptor-binding protein engineering for host-range expansion, and targeted delivery platforms designed to improve phage stability and site-specific activity in the stomach. Finally, we highlight key translational barriers, including biosafety evaluation, functional validation, and in vivo efficacy. Together, these advances provide a framework for evaluating phage-based and phage-derived antimicrobial strategies for H. pylori control, while highlighting the need for rigorous functional validation, biosafety assessment, and in vivo efficacy testing.
To investigate whether muscle strength changes observed in randomised controlled trials involving people with patellofemoral pain (PFP) are associated with concurrent changes in pain and physical function. Systematic review with meta-analysis, applying a two-stage structural equation modelling approach with random-effects estimation. Randomised clinical trials assessing non-surgical and non-pharmacological interventions that reported both muscle strength and at least one clinical outcome (pain or function) in people with PFP. CINAHL, Cochrane Library, Embase, Medline and SPORTDiscus were searched from inception to April 2026. From 16,750 records screened, 82 trials met the eligibility criteria (4023 participants). Regarding self-reported pain outcomes, low to moderate evidence certainty indicated significant associations between strength improvements and pain reduction for knee extensors (r =  - 0.75, β =  - 0.21), knee flexors (r =  - 0.46, β =  - 0.14), hip abductors (r =  - 0.91, β =  - 0.31), hip adductors (r =  - 0.26, β =  - 0.19), hip external rotators (r =  - 0.24, β =  - 0.06), hip internal rotators (r =  - 0.79, β =  - 0.31) and hip extensors (r =  - 0.58, β =  - 0.26). Regarding self-reported function, low to high evidence certainty indicated that strength improvements in knee extensors (r = 0.70, β = 0.15), knee flexors (r = 0.46, β = 0.07), hip abductors (r = 0.94, β = 0.15), hip adductors (r = 0.55, β = 0.11), and hip internal rotators (r = 0.98, β = 0.06) were significantly associated with improved function. This review provides evidence that improvements in lower limb muscle strength are associated with improvements in pain and physical function among people with PFP. These findings reinforce the clinical relevance of strength-focused rehabilitation, particularly targeting the knee and hip muscles. CRD42023420875.
Dose administration aids (DAAs) support medication taking, yet little is known about how pharmacists perceive DAA benefits and challenges. This study aimed to explore community pharmacists' preferences for attributes of a DAA service and how these influence their decision to provide this service. A discrete choice experiment (DCE) was conducted to elicit pharmacists' preferences. Participants completed 12 choice questions, each presenting three alternatives: two DAA services and no DAA service. The questions included seven attributes: patient type, patient control over their medicines, impact on patient medication adherence, staff time, patient co-payment, government reimbursement fee and presence of a cap on government funded DAA services per pharmacy. A total of 615 community pharmacists completed the DCE survey. All attributes, except patient type and co-payment, significantly influenced preferences. Pharmacists were more likely to provide a DAA service (compared with no DAA service) when it was associated with higher government funding (pharmacy owners: OR 1.054, 95% CI 1.046-1.063, p < 0.001; non-owners: OR 1.041, 95% CI 1.036-1.046, p < 0.001). Pharmacists were less likely to provide a DAA service if there was a cap on the number of funded DAA services (OR 0.905, 95% CI 0.862-0.950, p < 0.001), or additional staff time was required (OR 0.981, 95% CI 0.976-0.986, p < 0.001). This DCE identified two key policy-related barriers to pharmacist provision of DAA services: inadequate government reimbursement and caps on the number of funded DAA services. These findings highlight community pharmacists' preferences and trade-offs, offering valuable guidance to inform future redesign and implementation of more sustainable and equitable DAA services provided via community pharmacy.
Hip fracture is common among older adults and is associated with considerable morbidity and mortality; it is nearly twice as common in those with dementia, who may also experience worse postfracture outcomes. Time spent at home is an important quality-of-life indicator, but this outcome has not been previously examined following hip fracture in older adults with and without dementia. To compare days at home and survival for the year after hip fracture among older adults with and without dementia and to identify factors associated with fewer days at home among those with dementia. This longitudinal cohort study used national administrative data from 100% of Medicare beneficiaries from 2012 to 2021 to identify community-dwelling older adults (aged ≥65 years) with and without dementia hospitalized for a hip fracture. Data were analyzed from January 1, 2012, to December 31, 2021. Hip fracture hospitalization. Days at home and survival at 30 days, 6 months, and 1 year after hip fracture. Among 1 756 388 Medicare beneficiaries hospitalized for hip fracture, the mean [SD] age was 82.5 [8.1] years, 1 237 193 (70.4%) were female, 65 889 [3.8%] were Black or African American, 93 362 [5.3%] were Hispanic, 1 547 090 [88.1%] were non-Hispanic White, and 513 698 (29.2%) had dementia. In the year following hip fracture, older adults with dementia died 50.3 days earlier than those without dementia (adjusted mean [SD] days, 264.6 [143.2] vs 314.9 [107.3]). Those with dementia who survived 1 year after fracture had 53.9 fewer days at home compared with those without dementia (adjusted mean [SD] days, 263.8 [129.5] vs 317.7 [72.9]) due to more time in skilled nursing (adjusted mean [SD] days, 38.2 [55.8] vs 24.2 [37.4]) and long-term care facilities (adjusted mean [SD] days, 52.5 [111.5] vs 12.4 [53.7]). Findings were similar at 1 and 6 months. Among individuals with dementia, Medicaid eligibility, rural residence, geographic region, and being aged 85 years or older were associated with the fewest days at home at 1 year. In this cohort study, older adults with dementia had shortened survival and more time in skilled nursing or long-term care facilities after hip fracture than those without dementia. Differences in days at home were associated with structural and socioeconomic factors among those with dementia, with implications for health system policy, prognostic counseling, and discussions about long-term care needs in this population.
Hypertriglyceridemia-induced acute pancreatitis is associated with high triglyceride levels and may lead to significant clinical complications. Rapid TG-lowering strategies, including insulin, therapeutic plasma exchange (TPE), heparin, hemofiltration, and conservative management, are used in clinical practice; however, their comparative efficacy and impact on clinical outcomes remain uncertain. Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and International Prospective Register of Systematic Reviews (PROSPERO) registration (CRD420251239674), we searched PubMed, Embase, Web of Science, Scopus, CINAHL, Google Scholar, and Cochrane. Primary outcomes included TG reduction, C-reactive protein (CRP), length of stay, mortality, and organ failure. Secondary outcomes included renal and respiratory failure. Random-effects network meta-analyses estimated mean differences or relative risks with 95% confidence intervals; treatments were ranked using the Surface Under the Cumulative Ranking curve (SUCRA). Predefined sensitivity analyses were conducted according to study design (RCTs) and risk of bias (ROB). Across predominantly observational evidence, no intervention demonstrated statistically significant superiority over insulin-based therapy for mortality, organ failure, or length of stay, and no consistent clinical benefit was observed despite differences in biochemical TG reduction. Although some interventions showed relatively favorable SUCRA rankings across selected outcomes, these findings were not consistently supported by statistically significant or high-certainty evidence. In RCT-restricted analyses, therapeutic plasma exchange (TPE) significantly reduced TG levels versus insulin (MD - 620.0; p = 0.03) and CRP versus conservative therapy (MD - 0.80; p < 0.01), while insulin plus heparin was associated with shorter hospital stay (MD - 1.60 days; p < 0.01). However, faster triglyceride reduction did not consistently translate into improved mortality, organ failure, ICU-related outcomes, or length of stay. Despite improvements in biochemical markers, the clinical significance of rapid TG reduction in HTG-AP remains uncertain, as these effects were not consistently associated with improvements in mortality, organ failure, ICU-related outcomes, or hospital length of stay. Given that most available evidence was derived from nonrandomized studies and that the certainty of evidence was predominantly low or very low, adequately powered randomized controlled trials are needed to determine whether accelerated triglyceride lowering improves clinically meaningful patient outcomes.
Implanted microelectrodes offer a direct method for electrically interfacing with individual neurons in vivo. A major challenge preventing long-term deployment of such interfaces is the degradation of recording quality over time. This is especially evident when targeting deep brain structures, as surgical access is challenging and invasive, and depth probes are subjected to elevated levels of micro-motion. To address these challenges, miniaturization and biomimetic softness are emerging as effective strategies to improve stability and biointegration of neural implants. Here, we propose a penetrating probe design that couples the miniaturization, contact density, and manufacturability of microfabricated electrode arrays on flexible polyimide, with a micrometric soft-shell encapsulation. The latter leverages a zwitterionic hydrogel coating to achieve tissue-level mechanics and an anti-fouling surface. We design, develop, and validate a surgical insertion strategy and the associated tooling, enabling implantation of soft depth probes in the gigantocellular (Gi) nucleus of a rat model. We show stable, high signal-to-noise ratio neurophysiological recordings for at least 8 weeks. We further demonstrate a multimodal system to study the cortico-brainstem circuitry in transgenic mice using optogenetic cortical neuromodulation coupled to brainstem electrophysiology. Our results demonstrate that hybrid soft-flex microfabrication technology can increase the longevity and the quality of chronic neural recordings in hard-to-reach deep neural circuits.
The combination of hydrogels and polymeric nanoparticles (NPs) offers a versatile strategy to engineer multifunctional nanocomposite systems for advanced drug delivery applications. In this work, three amphiphilic block copolymers were synthesized through controlled/living polymerizations, affording macromolecules with distinct end-chain functionalities. These copolymers self-assembled into core-shell NPs, which were subsequently embedded within a cross-linked agarose-carbomer-hyaluronic acid hydrogel via physical, chemical, or ionic interactions. The incorporation of NPs within the hydrogel matrix enabled the co-delivery of both hydrophobic and hydrophilic therapeutic cargos, confining dexamethasone (DEX) in the hydrophobic NP core and a model protein within the water-rich hydrogel network. The resulting hybrid systems exhibited tunable rheological and NP release properties, depending on the NP surface moieties and the encapsulation method. Sustained DEX release was displayed over several days, and controllable protein release was achieved according to the NP surface properties. The nanocomposite showed excellent cytocompatibility, demonstrating a relevant reduction of pro-inflammatory cytokines expression in vitro. Overall, the proposed strategy highlights the potential of polymer chemistry-driven design to tailor hydrogel-NP interactions, providing a promising platform for targeted, sustained co-delivery of therapeutics suitable for several applications.
As intelligent electronics become increasingly integrated into daily life, health care, virtual interaction, and assistive systems, human-machine interfaces (HMIs) require sensing platforms that are not only wearable and self-powered but also capable of translating human signals into adaptive machine functions. Triboelectric wearable sensors are particularly attractive in this regard because they directly transduce human-generated mechanical stimuli, provide broad material and structural design freedom, and are readily adaptable to body-interfaced formats. In this review, wearability refers to body-mounted, skin-interfaced, textile-integrated, or otherwise human-attached triboelectric sensing platforms, whereas human-centric smart electronics refers to downstream electronic systems that remain functionally anchored to human-originated sensing, interpretation, feedback, or control. From this perspective, we review triboelectric wearable sensors from fundamentals to applications, covering working principles, material selection, device architectures, and fabrication strategies. We further discuss artificial intelligence-assisted signal processing, triboelectric artificial synapses, and neuromorphic computing as key bridges from self-powered sensing to intelligent HMI. Representative application spaces, including health care, gesture recognition, device control, immersive virtual interaction, wearable-to-robotic extensions, and intelligent transportation are discussed only when wearable triboelectric sensing serves as the primary human-input interface. Finally, the remaining challenges and future directions toward next-generation human-centric smart electronics are outlined.
Metal-organic cages are a class of excellent photocatalysts. In this work, TNC@Co and TNC@Fe were used as model systems to investigate the influence of metal nodes on the photocatalytic reduction of CO2. The catalytic activity of TNC@Co reaches 18.8 mmol g-1 h-1, which is 3.2 times higher than that of TNC@Fe. In situ FTIR spectroscopy revealed that, compared to TNC@Fe, TNC@Co generates and accumulates reaction intermediates more rapidly, thereby significantly enhancing photocatalytic performance. This study provides experimental evidence for the design of highly efficient photocatalytic systems and offers crucial support for advancing CO2 catalytic conversion technologies.
Growing rates of mental illness among the pediatric population have led to increased morbidity and mortality, with suicide being the second leading cause of death among children aged 10-14. Barriers to mental health (MH) care, including limited access to resources, stigma, and education, perpetuate the crisis. Pediatric primary care providers must seize every opportunity to bridge this gap. This project created an age-appropriate virtual educational program for adolescents aged 12 to 18 on the MH assessment tool, the Patient Health Questionnaire (PHQ-9), which is commonly used during well-child visits. A clinician‑authored slide deck was converted into a 10‑minute Articulate Storyline® module delivered on clinic tablets. Using a backward-design approach, every screen and interaction was mapped to four learning objectives focused on (1) feelings literacy, (2) PHQ-9 comprehension, (3) early-detection awareness, and (4) help-seeking efficacy. As a clinician-designed module not yet formally deployed to the target population, formative feedback was limited to informal review by four adolescent testers prior to final release. Teen testers who reviewed the material requested shorter card-back text, an option to replay narration, and higher color contrast on negative-emotion cards. By grounding the module in the validated PHQ-9 screening tool and evidence-based instructional design principles, and by engaging key stakeholders, the interactive virtual educational program bridges critical MH gaps by educating and empowering adolescents to understand their mental well-being and proactively engage in their care.
Collagen remodeling is an emerging hallmark of breast cancer progression, offering profound insights into tumor biology and therapeutic vulnerability. While breast cancer has long been understood through the lens of genetic mutations and cellular deregulation, recent advances have emphasized the crucial role of the tumor microenvironment (TME), particularly the extracellular matrix (ECM), in directing cancer progression. As the most prevalent structural protein within the ECM, collagen plays a key role in tissue mechanics, cell signaling, and immune regulation. This review examines the current understanding of the molecular configuration and diversity of collagen types found in breast tissue, with an emphasis on the pathological alterations that occur during malignant transformation. We explore how enzymes, such as matrix metalloproteinases (MMPs) and lysyl oxidase (LOX), regulate collagen degradation and crosslinking. These processes drive ECM stiffening and the formation of aligned collagen fibers, which promote tumor invasion, angiogenesis, and immune evasion. This article also highlights tumor-associated collagen signatures (TACS) as potential diagnostic biomarkers and evaluates advanced imaging modalities, including techniques like second harmonic generation (SHG) microscopy and magnetic resonance elastography (MRE), which enable in vivo assessment of collagen remodeling. Furthermore, we review therapeutic approaches targeting collagen-modifying enzymes and emerging nanoparticle-based delivery systems designed to disrupt the fibrotic ECM and improve drug penetration. Ultimately, collagen is now recognized not merely as a structural scaffold, but as an influential factor actively involved in the progression of breast cancer. Understanding the mechanisms and clinical implications of collagen remodeling may open novel paths for personalized diagnostics and targeted therapies, offering new hope for the management of aggressive and treatment-resistant breast cancers.
Chicken astrovirus (CAstV) infections cause significant economic losses in global poultry production through nephritis, enteritis, and growth retardation, yet commercial vaccines remain unavailable. This study evaluated a novel inactivated CAstV vaccine's capacity to induce protective maternal antibodies in specific-pathogen free breeder chickens and subsequent progeny protection. One hundred SPF breeder chickens received two dose vaccination (10 and 16 weeks) with inactivated vaccine containing Genogroup B strain IP2024-00664 (GenBank: PX146716.1, complete ORF-2 capsid protein gene, 2,247 bp). Comprehensive serological monitoring used validated ELISA protocols. Progeny underwent controlled challenges at 3 days post hatch with homologous IP2024-00664 and heterologous ASN/CAstV/EG/2025 (nephropathogenic Genogroup B strains) using 10 chicks per group. Endpoints included clinical protection, viral suppression, histopathological changes, and economic parameters analyzed using Cox proportional hazards models, Kaplan-Meier survival analysis, and cost effectiveness modeling. Vaccinated breeders demonstrated exceptional immunological responses with peak antibody titers of 14,350 ± 1,892 versus baseline 35 ± 8 (P < 0.001). Maternal antibody transfer ratio reached 125%. Progeny achieved complete clinical protection with 100% survival rates (20/20) against both challenges compared to control groups showing 0% survival (0/10, heterologous challenge) and 30% survival (3/10, homologous challenge) (P < 0.001). Quantitative RT-PCR confirmed functional sterilizing immunity with viral RNA levels below the assay detection limit in vaccinated groups. Cost effectiveness analysis revealed favorable return on investment (base-case ROI: 187% per protected bird; sensitivity range: 62-312%) with break even at 0.27% mortality prevention. This inactivated CAstV vaccine successfully induced high titer, transferable maternal antibodies providing functional sterilizing immunity against phylogenetically distinct nephropathogenic challenges.
The chiral-induced spin selectivity (CISS) effect offers a novel paradigm for designing high-performance catalysts for spin-dependent oxygen evolution reactions (OER). Layered double hydroxides (LDHs), are widely used for oxygen evolution reaction (OER) due to their superior electrocatalytic activity and stability in alkaline environments. Here, we demonstrate that intercalating chiral phenylalanine molecules into CoFe-LDH induces spin-polarized OER via the CISS effect, while simultaneously expanding the interlayer spacing. The resulting chiral-inorganic hybrid interface directs the reaction along a lower-energy pathway, promoting the formation of triplet O2, and exhibits outstanding OER performance with a lower overpotential of 245 mV at 10 mA cm-2, as well as faster charge-transfer kinetics compared to its achiral counterpart. Using in situ XANES, in situ Raman spectroscopy, and nanoscale scanning electrochemical cell microscopy (SECCM), we further uncover the fundamental origin of this chiral-induced spin-selective behavior. This study establishes a general strategy for designing advanced, stable oxide-based electrocatalysts, where intercalated chiral molecules manipulate spin dynamics to improve reaction kinetics and selectivity.