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The Hippo signaling pathway prevents unchecked cell growth, coordinates apoptosis, and preserves proper organ function. Dysregulation of this pathway has been implicated in a myriad of diseases, particularly in cancer. The YAP (Yes-associated protein)-TEAD (TEA domain transcription factor) complex, the key transcriptional downstream effector of the Hippo pathway, hence stands out as an appealing target for therapeutic intervention. In this study, we developed a high-throughput screening (HTS) assay leveraging phase separation principles and found that the US Food and Drug Administration-approved clinical drug cobimetinib is a potent inhibitor of the YAP-TEAD complex. Cocrystallization studies of cobimetinib with TEAD showed that cobimetinib bound to the TEAD lipid pocket and disrupted TEAD palmitoylation. Cobimetinib could overcome resistance to mitogen-activated protein kinase kinase 1/2 inhibitors and to the first-line drug sorafenib in vivo. In addition, cobimetinib suppressed tumor growth and tumorigenesis associated with hyperactivated YAP-TEAD activities in a mouse model of lung cancer. Furthermore, it bolstered the efficacy of the first-line drugs sorafenib and lenvatinib in inhibiting both hepatocellular carcinoma tumor growth and tumorigenesis. These findings establish a strategy for identifying and refining inhibitors of the YAP-TEAD complex in the treatment of cancers driven by aberrant YAP-TEAD activity.

Recent trials have shown that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dual gastric inhibitory polypeptide/GLP-1 RAs improve symptoms and functional capacity in patients with heart failure (HF) with preserved ejection fraction and obesity, with or without type 2 diabetes. These studies enrolled modest sample sizes and had few worsening HF events or cardiovascular (CV) deaths, limiting definitive conclusions regarding those endpoints. At the same time, the benefits of these drugs on major adverse CV and kidney outcomes in patients with obesity, diabetes, and chronic kidney disease raise questions about placebo-controlled designs in future HF trials. This article explores scientific, practical, and ethical considerations surrounding the design of future incretin-based therapy trials in HF. We highlight the current gaps in evidence and emphasize the need for event-driven outcome trials in HF. The use of placebo ensures methodologic rigor but may raise ethical concerns in the context of cardiometabolic benefit with GLP-1 RAs. Abandoning placebo, however, risks incomplete safety and efficacy data and premature therapeutic extrapolation. Such studies are essential to define the efficacy, durability, and safety of incretin-based therapy across the HF spectrum and to clarify whether improvements in patient-reported outcomes are bolstered by other benefits. To support balanced decision making, we introduce a structured framework outlining when placebo remains appropriate, when active comparison may be required, and how trial design features can address the ethical and operational challenges unique to incretin-based HF research. Ethically robust, clinically focused, and methodologically rigorous trials remain the only means to inform guideline recommendations and insurance coverage. The HF population is too large, too vulnerable, and too costly to remain without definitive evidence guiding the use of these therapies.

Extranodal natural killer/T-cell lymphoma (ENKTL) is clinically characterized by destructive lesions that first appear in the nasal cavity and progress along the midline of the face. It was historically described as "rhinitis gangrenosa progressiva" or "lethal midline granuloma" due to its destructive clinical nature and had significant diagnostic and therapeutic challenges. This review synthesizes about 40 years of research, beginning with the 1980s and 1990s, when the disease was identified as a T-cell- or NK-cell-derived lymphoma, and the authors' discovery that clearly linked it to Epstein-Barr virus (EBV). ENKTL is highly prevalent in East Asia and characterized by a type II EBV latency pattern, in which the oncoprotein latent membrane protein 1 (LMP1) acts as a central driver of pathogenesis, activating critical signaling pathways including JAK/STAT, NF-κB, PI3K/Akt, and RAS/MAPK. These pathways, often bolstered by mutations in genes, trigger an oncogenic cascade involving epigenetic modifiers-enhancer of zeste homolog 2 (EZH2), histone deacetylase (HDAC). The deletion of chromosome 6q, leading to loss of function of tumor suppressor PR domain zinc finger protein 1 (PRDM1) and forkhead box O3 (FOXO3), as well as transcription of TNF α-induced protein 3 (TNFAIP3) and protein tyrosine phosphatase receptor type kappa (PTPRK), also contributes to pathogenesis. In vitro studies by the author's group demonstrated that autocrine/paracrine positive feedback loops involving several pro-proliferative molecules/cytokine/chemokine-CD27, ICAM1, hepatocyte growth factor (HGF), IL-9, IL-10, IL-15, CCL17, CCL22, CXCL10- further amplify ENKTL proliferation. Diagnostic precision has improved through the use of serum EBV DNA copy numbers and viral microRNAs (miRs), specifically miR-BART2-5p, alongside the emergence of soluble CD27 as a novel biomarker. While early anthracycline-based regimens failed due to multidrug resistance (MDR), modern concurrent chemoradiotherapy composed of MDR-independent drugs has significantly improved 5-year overall survival (OS) rates for localized disease to over 80%. For advanced or relapsed/refractory cases, L-asparaginase-based regimens are standard, though outcomes remain unsatisfactory. The therapeutic paradigm is currently shifting toward chemoradiotherapy combined with either immune checkpoint inhibitors or small-molecule drugs. Future research should focus on novel molecular-targeted therapies, immunotherapies, or combination strategies targeting proliferation-related molecules or LMP1.

The metabolic processes of illicit substances are crucial within the realm of forensic toxicology, affecting the detection, analysis, and interpretation of drugs in legal and investigative contexts. Substances like opioids, cannabinoids, hallucinogens, benzodiazepines, and novel psychoactive substances (NPS) experience metabolic alterations primarily through Phase I (oxidation, reduction, hydrolysis) and Phase II (glucuronidation, sulfation) transformations. Fundamentally governed by cytochrome P450 (CYP) enzymes, they significantly influence the detectability and potential toxicity of the compounds. Specific metabolites, including 6-monoacetylmorphine (6-MAM) derived from heroin, benzoylecgonine originating from cocaine, and THC-COOH from cannabis, act as essential forensic indicators that assist in identifying patterns of substance use, recent exposure, or post-mortem drug redistribution. Nonetheless, drug metabolism exhibits substantial variability influenced by factors such as genetic polymorphisms, fluctuations in enzyme activity, and drug interactions, which can complicate forensic evaluations. Particularly those associated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high-resolution mass spectrometry (HRMS), have significantly bolstered the accuracy and consistency of drug identification across biological specimens like blood, urine, hair, and vitreous humor. This manuscript explores the forensic significance of drug metabolism and underscores its relevance in workplace drug testing, cases of impaired driving, and post-mortem toxicological investigations.

Despite their ecological risks, the seasonal mobility and co-release mechanisms of tungsten (W) and antimony (Sb) in macrophyte-dominated sediments remain poorly understood, as prior research has predominantly focused on static monitoring in agricultural soils or algae-dominated waters. This study addresses this knowledge gap by elucidating how aquatic macrophytes and heterogeneous DOM regulate the seasonal dynamics of W and Sb. Results identify sediments as a perennial W source peaking in spring and summer, whereas Sb exhibits distinct source-sink transitions, acting as a source only in summer. In spring, humic-like DOM facilitates W mobilization from Fe/Mn (oxyhydr)oxides via electron transfer and competitive adsorption. In contrast, initial Sb mobilization via tryptophan-like DOM complexation is superseded by re-adsorption onto Fe/Mn oxides, leading to net fixation. Seasonal trends further indicate that summer chlorophyll-a peaks drive transient metal uptake by vegetation. While Fe/Mn redox dynamics govern W release during autumn and winter, winter Sb mobilization is triggered by the oxidation of Sb(III) to mobile Sb(V), a pathway potentially bolstered by rhizospheric oxygenation. These findings establish a robust, quantitative framework for the differentiated management of strategic metalloids.

The Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE)2 trial builds on the foundational STAMPEDE trial, which introduced innovative multiarm treatment protocols for metastatic prostate cancer. This survey assessed Nigeria's readiness for the STAMPEDE2 trial by evaluating current clinical practices, radiotherapy infrastructure, systemic therapy usage, and imaging capabilities across its six geopolitical zones. We mapped the radiotherapy centers and machines currently available (commissioned) and in the Nigerian pipeline. A structured questionnaire comprising 31 questions in six sections was disseminated to clinical and radiation oncologists via Google Forms. The survey ran from July to September 2024, gathering data on radiotherapy availability, systemic therapies, advanced imaging, and readiness for clinical trial participation. Descriptive statistical analysis was conducted using Microsoft Excel. Responses were aggregated from 14 cancer centers across Nigeria, encompassing both public and private facilities. The survey identified 23 operational radiotherapy machines distributed across 12 centers, with 19 additional facilities in the pipeline. These centers were predominantly located in urban areas such as Lagos and Abuja. Prostate cancer treatment modalities are available; however, access to agents such as abiraterone and enzalutamide was reported in 73% of centers. There is one operational positron emission tomography/computed tomography facility in Nigeria. Clinicians expressed strong interest in participating in trials although some gaps in infrastructure, particularly in rural areas, and limited access to advanced treatments like 177Lu-PSMA-617 were noted. The findings underscore Nigeria's potential readiness for the STAMPEDE2 trial, other clinical trials, and collaborative research, bolstered by an expanding radiotherapy infrastructure and clinician enthusiasm for advanced therapeutic approaches. Initiatives like the Cancer Health Fund and the National Cancer Access Partnership represent significant steps toward equitable cancer care.

SUMMARYRespiratory syncytial virus (RSV) continues to be a significant global health concern, particularly affecting infants, young children, and older adults. Although the virus was discovered decades ago, a complete cure remains elusive. RSV is a leading cause of lower respiratory tract infections, contributing to significant illness and mortality around the world. Recent scientific advances have brought promising developments in the fight against RSV. Progress in vaccine technology has led to the approval and distribution of preventative vaccines, particularly for high-risk groups. Monoclonal antibodies, designed to target and neutralize the virus, are used both to prevent and treat infections. Antiviral treatments, though still limited, are also showing potential in reducing disease severity and duration. Advanced animal and controlled human infection models have bolstered preclinical and clinical research, allowing for the testing and refinement of therapeutic candidates in more physiologically relevant systems. These models are playing a crucial role in understanding disease mechanisms and evaluating the efficacy of new interventions. As the field rapidly evolves, it is essential to pause and assess our current standing in the fight against RSV. In many ways, we are finally catching our breath-equipped with better tools and a deeper understanding, yet still facing the challenges of a persistent and complex virus. Continued innovation, investment, and global collaboration will be essential to translate these developments into widespread therapy for those most vulnerable to RSV.

The HA&BC-SRB composite, formed by immobilizing sulfate-reducing bacteria (SRB) onto a hybrid of humic acid (HA) and biochar (BC), achieved effective remediation of cadmium (Cd) and lead (Pb) through synergistic physicochemical and biological processes. The carrier provided a favorable microenvironment for bacterial activity (3.82 × 10⁸ CFU g⁻¹), with maximum adsorption capacities of 210.92 mg g⁻¹ for Pb and 137.04 mg g⁻¹ for Cd. Removal occurred primarily via monolayer chemisorption, involving sulfate reduction, extracellular polymeric substance complexation, and enzymatic electron transfer leading to stable sulfide precipitation. Immobilization induced substantial transcriptional reprogramming of metal detoxification and metabolic genes, accompanied by a metabolomic shift characterized by enhanced tricarboxylic acid cycle activity, oxidative phosphorylation, and glutathione metabolism. These changes collectively bolstered energy supply and antioxidant capacity. A strong correlation between differentially expressed genes and altered metabolites revealed a well-coordinated molecular network supporting biomineralization while preserving cellular integrity. This gene-metabolite coupling directly fuels the energy-intensive processes of sulfide precipitation and metal efflux, thereby enhancing biomineralization efficiency. Multi-omics integration confirmed that the carbon carrier primes SRB into a metabolically pre-adapted state, enabling a rapid and robust stress response. In soil trials, the system effectively transformed bioavailable heavy metals into stable residual fractions, reducing Cd and Pb accumulation in pakchoi plants by up to 85.12% and 66.88% respectively. These findings demonstrate that inducing a pre-adapted state in SRB through a functionalized carbon carrier offers a promising strategy to enhance bioremediation efficacy in metal-contaminated soils.

We examined racial/ethnic, age, and gender differences in changes in total household income and wealth among U.S. older adults and further evaluated whether change in sense of purpose in life (SPIL) moderates these differences. Data were from the 2012-2018 waves of the Health and Retirement Study (N = 7,505). We estimated multivariate ordinary least squares regression models with interaction terms to evaluate the moderation effects of changes in SPIL on the differences in changes in income and wealth, adjusting for health and sociodemographic characteristics. Differences in household income and wealth persist, varying across race/ethnicity, age, and gender groups. Non-Hispanic Black, Asian/other, and Hispanic older adults, as well as women, had significantly lower household income and wealth. Multiple moderation analyses demonstrated that changes in SPIL moderated racial/ethnic and gender differences in income, functioning either as a buffer or an amplifier, but had no effect on wealth. Specifically, increased SPIL was protective against lower income among women and Hispanic older adults. However, its beneficial effect was significantly attenuated among non-Hispanic Asian/other older adults, suggesting the psychological benefits of SPIL may not uniformly impact financial outcomes across racial/ethnic groups in later life. Our findings highlight the need to consider cultural contexts in psychosocial influences on late-life financial well-being through a life-course perspective and to develop culturally informed strategies to reduce financial inequities in aging populations. Our findings suggest promoting SPIL may bolster financial resilience, particularly among Hispanic older adults and women.

This study aimed to examine the associations of childhood trauma, psychosocial resources (social support and resilience), and emotional distress with quality of life (QoL) in patients with functional dyspepsia (FD), and to explore potential differences between the epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) subtypes. This cross-sectional study included 152 FD patients and 79 healthy controls who completed the Korean versions of the following instruments: Beck Depression Inventory-II (K-BDI-II), Beck Anxiety Inventory (K-BAI), Childhood Trauma Questionnaire (KCTQ), Multidimensional Scale of Perceived Social Support (MSPSS), Connor-Davidson Resilience Scale (CD-RISC-K), and World Health Organization Quality of Life Assessment Instrument Brief Form (WHOQOL-BREF). Negative affect was computed as a principal component analysis-derived composite from K-BDI-II emotional/cognitive items and K-BAI; QoL was a composite of WHOQOLBREF domains. Group differences were assessed using analysis of variance, and hierarchical regression analysis identified predictors of QoL within the patient group. Finally, multivariate regression models compared subtype-specific psychosocial associations. Compared to controls, patients with FD reported higher emotional distress and childhood trauma, lower psychosocial resources and QoL. Negative affect was consistently associated with lower QoL in both subtypes (EPS: β=-0.360; PDS: β=-0.300). Although direct statistical comparison of pathways between subtypes showed no significant differences, the most prominent protective factor within each group appeared to differ: in the EPS group, higher social support was the most significant predictor of better QoL (β=0.381, p=0.001), whereas in the PDS group, resilience was the key protective factor (β=0.360, p=0.001). Reducing emotional distress remains a central target for improving QoL in FD. Subtype-tailored emphases may be helpful- enhancing social support in EPS and bolstering resilience in PDS-while noting that between-subtype differences were limited and require confirmation in larger samples.

While emergency preparedness preparations are typically focused on the most commonly occurring events such as natural disasters, disease outbreaks, and small-scale human-made disasters, concern for disasters involving mass gatherings is growing, particularly with previously less common nuclear, radiological, and explosive incidents. An example is provided of potentially useful preparedness for these events with the upcoming FIFA World Cup 2026TM, expected to be one of the largest sporting events in USA history. Trainings and protocols are reviewed, with a specific suggestion of a scorecard for prioritizing preparedness. Particular focus is also given to integrated surge pathways in this response. By combining evidence-based risk communication, burn surge planning, and the scorecard approach to prioritize and coordinate actions across host cities, organizers can reduce preventable morbidity and mortality.

In this case series, the authors aim to illustrate a technique for reinforcing tissue above deep-brain stimulator (DBS) surgical sites to prevent wound breakdown and decrease postoperative infectious risks. Twelve patients were implanted with DBS electrodes and an implantable pulse generator. Fish acellular dermal matrix was utilized following successful placement and tunneling of DBS leads to reinforce the surgical wound closure above the DBS cranial burr hole cover. This matrix was placed under the galea and above the pericranium in each patient before standard galea and skin closure techniques after the implants were placed. Eleven of 12 patients had the implant placed during surgery. One patient was excluded due to an allergy to the graft material. No patients at any point during the follow-up period showed any clinically significant signs of wound breakdown or infection at the surgical site. There was one report of suture extrusion without any associated infection or wound breakdown. In this case series, the authors demonstrate that the use of fish skin acellular dermal matrix is a safe and effective strategy that can be utilized during DBS placement to further bolster the skin above DBS burr hole covers to aid in wound healing and decrease postoperative surgical site infections.

This systematic review aims to synthesize what protective factors have been identified to promote resilience in adults who have experienced potentially traumatic events (PTEs). APA PsychInfo and PubMed were searched to identify literature published between 2014 and 2024 that studied resilience in trauma-exposed adults. Studies were included if: the PTEs experienced by participants met Criterion A for events preceding posttraumatic stress disorder as outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Text Revision (DSM-V TR); the study measured modifiable protective factors; and the study included a measure of resilience. Two independent reviewers used standardized data extraction forms and assessed risk of bias with the Mixed Methods Appraisal Tool. Of 991 unique references, 13 articles met inclusion after full-text review. A social-ecological framework guided the synthesis and categorization of factors bolstering resilience. At the interpersonal level, protective factors identified included social support and religious attendance. At the institutional or organizational level, employment, length of employment, and workplace belongingness were identified as promoting resilience. At the community level, access to social resources to help meet basic needs was found to strengthen resilience. Finally, at the public policy level, employee assistance supported resilience. This review identified critical gaps in current resilience literature. Future research should define the type, timing, and duration of PTEs exposure, as well as specify the time lapsed between data collection and the PTEs exposure. Resilience conceptualizations and interventions should focus on tracing resilience across time and on multisystemic resilience-oriented interventions that include the individual, interpersonal, institutional/organizational, community, and public policy levels.

Recent research has proposed that healthcare providers should use the five resilience communication processes from the communication theory of resilience (CTR) to better meet the goals of patient-centered communication and avoid manipulative communication. The current research assesses the connection between healthcare providers' resilience communication (HPRC) and patients' perceived physical health. The study uses a more comprehensive measure of perceived physical health validated by the World Health Organization and tests trust as a mechanism of effect. Participants (N = 307) were recruited through Qualtrics panels into a cross-sectional survey study, asking about their communication with healthcare providers over the last year. Participants responded to items about HPRC, trust in healthcare providers (including perceived provider competence, goodwill, and morality), and perceived physical health. Analysis included linear regression models controlling for age and number of healthcare visits to test associations with each of the five HPRC processes and structural equation modeling using a second-order latent HPRC variable. The HPRC processes were all positively related to perceived physical health and trust. HPRC was indirectly, positively related to perceived physical health through trust. HPRC may be an effective strategy for improving patients' health via increased trust in healthcare providers. All five processes are likely helpful. The findings both bolster and complicate prior work on HPRC, pointing to a need for further research. HPRC should be integrated into clinical practice. Training for healthcare providers modeling how to implement the five processes would be beneficial. Members of the healthcare team should be designated to discuss how treatment/symptoms fit into patients' daily routines and to connect patients with support networks. Patient satisfaction surveys should include trust to best assess effectiveness of healthcare provider communication.

Immune-checkpoint inhibitor (ICI) related encephalitis (ICI-IE) is a severe adverse event, associated with high morbidity and mortality and requiring prompt ICI discontinuation. The safety of rechallenge with ICI after initial adverse event is largely unknown and must be considered only after cautiously weighing risks and benefits of resuming treatment. A 66-year-old otherwise healthy female was diagnosed with localized renal cell carcinoma, which was treated with immunotherapy, ipilimumab/ nivolumab. After the second cycle of treatment, she developed subacute progressive personality changes, memory loss and encephalopathy, and was diagnosed with CTCAE grade III immune-related limbic encephalitis. Her chemotherapy regimen with ipilimumab and nivolumab were promptly discontinued and she was treated with seven days of intravenous solumedrol with prolonged oral steroid taper. Four years later, she had recurrent metastatic disease, prompting the decision to pursue palliative immunotherapy with cabozantinib and immune checkpoint rechallenge with Nivolumab. Given her history of ICI-IE, neuroimmunology was consulted to discuss risks of rechallenge with ICI. Over 9 months after initiation of therapy, she remained without recurrence of immune-related adverse events (irAE) related to treatment. We present one of the first reports of successful rechallenge of immune checkpoint inhibition after ICI-IE in the setting of recurrent metastatic renal cell carcinoma. This treatment success may bolster the management options for refractory oncologic disease. Given potential risks associated with ICI rechallenge, it is imperative to employ a multidisciplinary approach with consideration of potential risks and benefits of treatment.

This study aimed to examine the association between positive solitude (PS) and life orientation among Chinese college students, and the mediating role of self-esteem and the moderating role of hope in this relationship. A cross-sectional survey was conducted among 830 Chinese undergraduate and graduate students. The validated instruments-including the Positive Solitude Behavior Scale (PSBS), the Life Orientation Test-Revised (LOT-R), the Adult Trait Hope Scale (ATHS), and the Rosenberg Self-Esteem Scale (RSES)-were used to assess the constructs of interest. Gender was included as a covariate in all analytical models. (1) After controlling for gender, positive solitude exhibited a significant positive direct effect on life orientation, (2) self-esteem significantly mediated the relationship between positive solitude and life orientation, and (3) hope moderated the first stage of this mediation pathway-specifically, higher levels of hope strengthened the positive association between positive solitude and self-esteem, thereby amplifying the indirect effect of positive solitude on life orientation through self-esteem. Positive solitude contributes to enhanced life orientation among college students both directly and indirectly by bolstering self-esteem. Moreover, dispositional hope is a salient psychological resource that intensifies this indirect pathway, underscoring its protective and facilitative function in promoting adaptive developmental outcomes.

The rise of antimicrobial resistance (AMR) demands therapeutic innovations that not only kill pathogens but also disarm their virulence and bolster host defenses. Organosulfur compounds (OSCs), with their unique integration of antimicrobial and immunomodulatory properties, offer a promising solution. Organosulfur compounds (OSCs) are emerging as dual-action candidates with antimicrobial and immunomodulatory potential, yet their translational readiness remains uneven across subclasses. This critical review synthesizes evidence published between 2010 and 2025 identified through targeted searches of PubMed Central, ProQuest, MDPI, ScienceDirect, and ClinicalTrials.gov, focusing on mechanistic, pharmacokinetic, and One Health-relevant dimensions. OSCs exert antimicrobial effects through thiol-reactive redox disruption, quorum-sensing inhibition, and suppression of virulence-associated transcriptional networks, with several agents demonstrating low-micromolar activity in vitro and measurable biofilm attenuation in preclinical models. Immunomodulatory actions-including Nrf2 activation and NF-κB suppression-are most consistently reported for isothiocyanates such as sulforaphane, which also possesses the strongest human pharmacokinetic dataset (peak plasma conjugate concentrations typically 0.one to two μM; urinary excretion >70% within 24 h). In contrast, thiosulfinates like allicin exhibit potent in vitro activity but are chemically unstable and seldom detectable in vivo, limiting systemic applicability without targeted delivery. Comparative assessment highlights significant evidence gaps: (i) absence of validated pharmacodynamic biomarkers for most OSC subclasses; (ii) limited structural optimization to mitigate off-target thiol reactivity; (iii) lack of controlled clinical trials evaluating infection-related outcomes; and (iv) scarce environmental fate data relevant to One Health frameworks. Together, these gaps underscore that OSCs should not be positioned as near-term therapeutic agents but as mechanistically rich leads requiring stabilization, standardized formulations, and biomarker-driven early-phase studies. This review provides a roadmap for advancing OSCs toward evidence-based antimicrobial and immunoregulatory interventions.

Mesenchymal stem cells (MSCs) have demonstrated significant potential in tissue regeneration; however, safety concerns remain a primary barrier to their clinical implementation. To further substantiate and expand upon these safety findings, an exhaustive safety evaluation was performed in non-human primates. No mortalities of cynomolgus monkeys were observed throughout the study. Aside from minor individual parameter fluctuations, no significant toxicological effects were observed in terms of general toxicity indicators, hematological profiles, biochemical analyses, urinalysis, immunological parameters, and macroscopic organ assessments. Both low- and high-dose haMSC groups exhibited mild to moderate inflammatory cell infiltration in the synovium. Biodistribution analysis revealed that haMSC gene copies were detectable exclusively at the injection site and were undetectable by 16 weeks post-final administration. This study affirms the safety profile of high-dose haMSCs following multiple intra-articular injections in non-human primates, offering robust safety data to bolster the clinical application of stem cell therapies in regenerative medicine.

The WHO Classification of Tumours (WCT) serves as a global standard for cancer diagnosis, providing a consistent framework by integrating clinical, histopathological, and molecular tumor characteristics, ensuring unified interpretation of diagnostic findings. Uniform terminology and standardized diagnostic criteria applied by WCT facilitates effective interdisciplinary communication, reduces variability in cancer diagnosis and reporting, enhances collection and comparability of cancer surveillance data, and supports clinical and epidemiological cancer research. The WCT informs the development of cancer screening programs and bolsters early detection strategies through the identification and classification of precursor lesions, playing a pivotal role across the cancer care continuum. Moving towards the sixth edition, the WCT adopts an increasingly multidimensional, interdisciplinary, and global approach. The program will actively contribute to the strategic planning and implementation of cancer prevention and early detection initiatives.