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Although pain response has been associated with overall survival (OS) in palliative radiotherapy for bone metastases, the prognostic impact of integrating pain response with changes in performance status (PS) and treatment-related adverse events (AEs) remains unclear. This study aimed to investigate their combined effects on OS in this context. This study included 361 patients treated with palliative radiotherapy for bone metastases between January 2013 and October 2024, with 1-year OS as the primary endpoint. A composite score was developed by assigning weights to pain response, PS change, and AEs based on their respective 1-year OS rates (point&#x2009;=&#x2009;OS%/10). Internal validation used bootstrap resampling (1,000 iterations). Incremental prognostic value was assessed using Net Reclassification Improvement (NRI). The score (range, 4.8-15.8) significantly stratified OS (p&#x2009;<&#x2009;0.001) with a C-index of 0.73. The composite model demonstrated superior discriminative performance compared with individual factor based on AUC comparisons (all p&#x2009;<&#x2009;0.001). NRI analysis showed incremental prognostic value of the composite model over pain response (p&#x2009;=&#x2009;0.017), PS change (p&#x2009;<&#x2009;0.001), and AEs (p&#x2009;<&#x2009;0.001). In conclusion, the scoring model incorporating pain response, PS changes, and AEs stratified OS-risk after palliative radiotherapy for bone metastases, providing incremental predictive value beyond pain response alone, but requires external validation before clinical application.

Alphanecrovirus tessellati and Alphanecrovirus oleae are closely related alphanecroviruses, sharing over 74% genomic identity and frequently co-infecting plants under natural conditions. Despite their frequent coexistence, the molecular consequences of single versus mixed infections, particularly concerning host RNA silencing responses, remain poorly understood. Here, we investigated the antiviral defense responses of Nicotiana benthamiana to single and mixed infections with both viruses, focusing on symptom development, viral accumulation, Dicer-like (DCL) gene expression, and virus-derived small interfering RNA (vsiRNA) profiles. Single infections resulted in contrasting disease phenotypes: A. oleae induced severe systemic necrosis and high viral accumulation, whereas A. tessellati caused transient infections with mild symptoms. In mixed infections, A. tessellati accumulated to significantly higher levels and was associated with enhanced disease severity, indicating that the interaction between the two viruses altered infection dynamics and favored A. tessellati accumulation. In contrast, A. oleae showed reduced relative genomic RNA accumulation in mixed infections despite the persistence of disease symptoms. Gene expression analyses showed consistent upregulation of DCL4 and DCL2 during mixed infection, supporting their involvement in antiviral RNA silencing under co-infection conditions. Small RNA profiling revealed infection-dependent differences in vsiRNA accumulation patterns. Notably, mixed infection was associated with a change in the predominant vsiRNA size class for A. oleae, alongside a shift in vsiRNAs genomic targeting from the RdRp gene during single infection to the suppressor-associated p6 gene during mixed infection, indicating a reprogramming of host silencing responses. Our results demonstrate that closely related viruses can differentially modulate host RNA silencing responses depending on the infection context. These findings highlight the plasticity of antiviral RNA silencing during viral co-infections and provide new insights into how mixed infections reshape host-virus interactions at the molecular level.

Annual immunisation against COVID-19 and seasonal influenza before the winter waves is increasingly recommended in routine practice. These vaccines may be administered on the same day or sequentially, yet data on the immunogenicity of consecutive vaccinations in patients on dialysis remain limited. In this real-world observational study, we assessed SARS-CoV-2-specific immune responses in dialysis patients receiving the monovalent XBB.1.5-vaccine followed by a quadrivalent influenza vaccine 14 days later, or either vaccine alone. Antigen-specific antibodies and T cells were quantified using enzyme-linked immunosorbent assays and flow cytometry. Baseline analyses showed that most patients had detectable SARS-CoV-2- and influenza-specific immunity prior to the vaccination season. Both vaccines substantially boosted pre-existing humoral and cellular responses. Among XBB.1.5-vaccinated patients, subsequent influenza vaccination did not alter the magnitude of spike-specific antibody or T-cell responses. Likewise, influenza vaccination had no non-specific effect on SARS-CoV-2-specific immunity. Spike-specific responses remained stable for six months and persisted at levels exceeding those of unvaccinated patients assessed during the same period. Sequential administration of COVID-19 and influenza vaccines in patients on dialysis is feasible and was not associated with compromised immunogenicity of either vaccine. These findings support the use of booster vaccination in these patients and inform future deployment of additional mRNA-based vaccines.

To evaluate the efficacy of the albumin-bilirubin (ALBI) grade, easy albumin-bilirubin (EZ-ALBI) grade and sarcopenia in predicting the prognosis of patients with unresectable hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) as monotherapy or in combination with Lenvatinib. Thirty-eight patients with Barcelona Clinic Liver Cancer (BCLC) stage B and 36 patients with stage C HCC received TACE and TACE with Lenvatinib, respectively. Tumor response was assessed according to the modified RECIST (mRECIST) criteria. ALBI, EZ-ALBI grades and sarcopenia were measured both prior to TACE and during follow-up. Prognostic outcomes were determined based on objective response rate (ORR), progression rate and progression-free survival (PFS). Appropriate statistical analyses were used; p&#x2009;<&#x2009;0.05 was considered significant. In stage B, ORR, tumor progression and PFS showed significant variation with ALBI grades (p&#x2009;=&#x2009;0.004, p&#x2009;=&#x2009;0.001, p&#x2009;<&#x2009;0.001), but not with sarcopenia (p&#x2009;=&#x2009;0.090, p&#x2009;=&#x2009;0.310, p&#x2009;=&#x2009;0.114). ORR exhibited no significant difference across EZ-ALBI grades (p&#x2009;=&#x2009;0.055), whereas tumor progression and PFS demonstrated significant differences (p&#x2009;=&#x2009;0.025, p&#x2009;=&#x2009;0.004). In stage C, ORR, tumor progression and PFS varied significantly according to ALBI grades (p&#x2009;=&#x2009;0.011, p&#x2009;=&#x2009;0.002, p&#x2009;<&#x2009;0.001) and were worse in patients with sarcopenia (p&#x2009;=&#x2009;0.006, p&#x2009;=&#x2009;0.039, p&#x2009;=&#x2009;0.012). Although ORR did not differ significantly across EZ-ALBI grades (p&#x2009;=&#x2009;0.158), tumor progression and PFS showed significant differences (p&#x2009;=&#x2009;0.033 and p&#x2009;<&#x2009;0.001). ALBI and EZ-ALBI grades demonstrated significant prognostic value for patients with intermediate-stage HCC undergoing TACE, as well as for those with advanced-stage HCC receiving TACE in combination with Lenvatinib. The presence of sarcopenia correlated with a poorer prognosis and diminished response in patients with advanced HCC treated with TACE and Lenvatinib; however, no definitive association was identified in patients classified as BCLC stage B following TACE.

Patients with advanced malignant adrenal tumors face poor prognoses with limited treatment options. Emerging data suggest that these rare tumors exhibit immunogenicity, potentially benefiting from intensified immunotherapy. The SPENCER trial (NCT04187404) evaluates EO2401, an off-the-shelf in vivo peptide immunotherapy containing three synthetic HLA-A*02 restricted-peptides called OncoMimic and derived from human gut commensals that exhibit molecular mimicry to tumor-associated antigens (BIRC5, FOXM1, IL13RA2) combined with nivolumab in patients with locally advanced or metastatic adrenocortical carcinoma (ACC) or malignant pheochromocytoma/ paraganglioma (PPGL). We performed T cell receptor (TCR) repertoire sequencing to profile the TCR architecture in ACC and characterize vaccination imprints. Here we show that ACC patients are characterized by a restricted peripheral T cell richness. EO2401 does not expand highly shared TCR clones across patients but diversifies pre-existing T cell clusters. These clusters are not converging on known neoantigen-specific TCRs but exhibit generation probabilities characteristic of public clones some of which being shared across patients. These findings suggest that EO2401-based peptide immunotherapy combined with checkpoint inhibition can broaden and activate public, pre-existing T cell clusters, potentially enhancing tumor-specific immune responses. Adrenal cancers are rare and often hard to treat. We wanted to understand whether a new cancer vaccine, called EO2401, can help the immune system recognize adrenal cancer. We studied blood samples from patients who received EO2401 together with nivolumab, a drug that can strengthen T cell responses against cancer. We found that patients with adrenal cancer had a reduced variety of T cells. After treatment, EO2401 appeared to diversify shared groups of T cells that may be able to recognize cancer-related targets. Our results suggest that EO2401 may help activate useful immune responses in adrenal cancer and should be explored further in future studies.

Sudden Cardiac Death (SCD) remains a leading cause of mortality worldwide, with outcomes critically dependent on the effective implementation of the "Chain of Survival" - early recognition, early CPR, early defibrillation, and post-resuscitation care. In regional and pre-hospital settings, systemic fragmentation between emergency dispatch, ambulance services, and hospitals undermines this chain. This study presents the development, implementation, and impact evaluation of an integrated, AI-enabled multi-modal emergency care system designed to strengthen the entire Chain of Survival for SCD in a regional context.: We designed and deployed a system integrating a unified information platform, IoT-enabled devices, point-of-care testing (POCT), and AI-driven clinical decision support. The system was implemented phased across three counties in Anyang, China (population&#x2009;&#x2248;&#x2009;2.1&#xa0;million) from January 2022 to December 2023. We conducted a quasi-experimental before-and-after study using routinely collected emergency medical services (EMS) data. Primary outcomes were median response time (call receipt to scene arrival), pre-hospital STEMI identification rate, and return of spontaneous circulation (ROSC) for out-of-hospital cardiac arrest (OHCA) of cardiac origin. Data from 1,208 emergency cases (pre-implementation: n&#x2009;=&#x2009;587; post-implementation: n&#x2009;=&#x2009;621) were analyzed. Interrupted time series (ITS) analysis was performed to control for secular trends. The median emergency response time decreased from 9.8&#xa0;min (IQR: 7.2-13.1) to 6.7&#xa0;min (IQR: 5.1-9.0) (P&#x2009;<&#x2009;0.001). The pre-hospital STEMI identification rate improved from 65% to 90% (p&#x2009;<&#x2009;0.01). For OHCA of cardiac origin, the ROSC rate increased from 18% to 31% (p&#x2009;<&#x2009;0.05), representing a 72% relative improvement. ITS analysis confirmed a significant level change for response time (&#x3b2; = -2.8&#xa0;min, 95% CI: -3.7 to -1.9, P&#x2009;<&#x2009;0.001) and for ROSC (&#x3b2; = +12% points, 95% CI: +5 to +&#x2009;19, P&#x2009;=&#x2009;0.01) immediately following implementation, with no significant pre-existing trends. The AI models demonstrated robust performance during validation (deterioration prediction AUC 0.89; STEMI detection AUC 0.92). The Anyang Model provides evidence that a systematically integrated, AI-driven platform is feasible and temporally associated with substantial improvements in regional emergency care for SCD. While causal attribution requires further validation, this systems-level approach offers a replicable framework that can be adapted to diverse resource settings.

Climate change increases the frequency and intensity of heat events. Previous studies have established a correlation between heat exposure and adverse pregnancy outcomes, including preterm birth, stillbirth, and other maternal and fetal health complications. However, evidence on the physiological pathways underlying heat strain during pregnancy and on whether heat adaptation strategies can modify these responses remains limited, particularly in low-resource settings. This study aims to assess the effects of environmental heat exposure on maternal and fetal physiological responses among pregnant women exposed and unexposed to a heat adaptation strategy. Physio-HeMAB is an interventional, cluster-randomized study hosted by the Health and Demographic Surveillance System in Navrongo, Ghana. This study integrates: (i) high-resolution environmental monitoring including Wet-Bulb Globe Temperature at household level and Universal Thermal Climate Index environmental data at regional level; (ii) continuous maternal physiological assessment via wearable devices measuring heart rate, heart rate variability, core body temperature, physical activity, and sleep; and (iii) fetal health assessments, including fetal heart rate and Doppler indices. This multimodal framework supports detailed assessment of how varying levels of environmental heat exposure relate to maternal physiological changes and fetal health indicators. Descriptive and multivariable statistical methods will be used to analyze the data. A better understanding of the physiological mechanisms of heat strain during pregnancy, and an evaluation of whether targeted adaptation strategies can mitigate its effects, are essential for protecting maternal and neonatal health. This Physio-HeMAB study integrates individual-level physiological responses to environmental heat exposure and heat adaptation strategies. This approach strengthens the evidence for developing context-specific and gender-responsive public health interventions. This study was registered in the Pan African Clinical Trials Registry as PACTR202601761543866 on 05 January 2026.

Behavioral decision-making tasks are widely used to study individual and social preferences, including risk-taking, temporal discounting, and cooperation-related choices such as social value orientation, trust, and reciprocity, as well as more complex social behaviors examined through social dilemma and coordination games. These tasks are often administered along with typical survey questionnaires. However, scripting complexity limits their implementation on some popular online survey platforms (e.g., Qualtrics), which are commonly used to deploy studies across large populations. Here, we share a detailed experimental protocol and the corresponding source code, which enable the modular implementation of a decision-making battery in Qualtrics, including tasks such as the social value orientation, prisoner's dilemma, trust game, and baseline nonsocial risk preference tasks. Data from 392 participants in Singapore and 94 participants in the United States&#xa0;(US) were collected and analyzed to validate the task battery. Their responses exhibited good quality and high convergent and divergent validity across different tasks and aligned with basic predictions of behavioral decision theory (e.g., the reflection effect and loss aversion) and social decision-making theories (e.g., inequity aversion and betrayal aversion). Responses from 314 Singapore participants and 94 US participants are shared (with their consent). The source code for the task batteries could be used to expand the database and for hypothesis testing in decision-making research. The data could facilitate comparisons with other populations and the development of simulated agents to address logistical challenges in asynchronous experiments. Overall, we go beyond mere code and data sharing to foster large-scale behavioral game theory research.

Dentin hypersensitivity is a common oral condition characterized by sharp pain triggered by exposed dentin in response to external stimuli, reflecting complex interactions between dentin structure, fluid dynamics, and neural responses, although its underlying biological mechanisms remain incompletely understood. Among the proposed mechanisms of dentinal nociception, the odontoblast transducer theory suggests that odontoblasts act as sensory cells capable of detecting stimuli and activating adjacent pulpal nerve fibers. This study aimed to characterize the scientific landscape of the odontoblast transducer theory through bibliometric and altmetric analyses. A bibliometric review was conducted using the Web of Science Core Collection and Scopus, without restrictions on publication year, language, or study design. Publication trends, citation metrics, journals, authorship, institutions, countries, keywords, and study designs were analyzed using VOSviewer and MapChart. A total of 65 studies were included, accumulating 1986 citations. Scientific output peaked in 2015, with Japan identified as the leading contributor. Altmetric data were retrieved from Dimensions to assess online visibility and dissemination. The highest Altmetric Attention Score reached 827, indicating substantial online dissemination of studies addressing molecular mechanisms. Most studies were in vitro and focused on molecular and cellular mechanisms, particularly transient receptor potential channels and ATP-mediated signaling. Research on the odontoblast transducer theory is concentrated in specific research groups and primarily addresses molecular mechanisms, highlighting the need for translational and clinically oriented investigations.

We examine how social behaviours emerge and stabilize across childhood. A sample of 537 Italian-speaking children (3-10 years) were randomly assigned to respond under time pressure (intuitive) or time delay (deliberative) in social decision tasks (Public Goods, Dictator, Ultimatum, Deception and Moral Dilemmas). Factor analysis identified three latent dimensions: Prosociality (cooperative, altruistic and honest actions), Social Optimism (beliefs about others' cooperation) and Acquiescence (tendency to accept offers). Intuitive responses were more prosocial than deliberative ones in early childhood (&#x3b2;&#x2009;=&#x2009;0.66; 95% CI = (0.35, 0.97)), but this difference diminished with age (&#x3b2;&#x2009;=&#x2009;-0.11; 95% CI = (-0.18, -0.05)). We found no evidence that Social Optimism varied across age or decision mode, whereas Acquiescence declined with age (&#x3b2;&#x2009;=&#x2009;-0.14; 95% CI = (-0.19, -0.10)). These findings suggest a developmental shift whereby prosocial behaviour is initially driven by intuitive responses and gradually becomes embedded within reflective, deliberative decision-making systems, as cooperative dispositions stabilize across childhood.

The open science movement has expanded expectations for transparency and reproducibility, yet the usability of shared datasets remains an underexplored barrier to cumulative science. In this study, we systematically examined 115 datasets from recent visual cognition publications to evaluate how core variables are labeled and documented. Across these datasets, we identified more than 3,000 unique column names, with most appearing only once, reflecting a lack of shared conventions. Even for foundational measures common to most experiments in the field (which we refer to as the "Big Four," i.e., participant identifiers, trial identifiers, response accuracy, and response times) we observed striking variability. Many datasets appeared to be un-curated exports from data collection software, often containing redundant or irrelevant variables, inconsistent coding schemes, or ambiguous column headings. Accessibility was also a recurring issue, with 28 datasets excluded from analysis due to broken links, restricted access, and interoperability issues arising from the use of closed file formats. To address these challenges, we propose concrete recommendations for standardizing column names, with specific guidelines for the Big Four variables, alongside broader suggestions for dataset curation, accessible file formats, and minimal documentation. We also introduce Output It Forward, a Chrome extension developed to streamline the identification of data availability statements and repository links. By highlighting inconsistencies in current practices and offering practical recommendations, our findings underscore that data sharing must go beyond availability to ensure usability. Clearer conventions and community standards will enhance the transparency, interpretability, and long-term value of shared datasets in visual cognition and beyond.

Tagraxofusp is a CD123-targeted therapy comprised of a recombinant human interleukin-3 (IL-3) fused to a truncated diphtheria toxin payload. It is the first approved treatment specifically for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). To identify biomarkers of response, bone marrow samples from 12 BPDCN patients who were treated with tagraxofusp in the pivotal phase II trial (NCT02113982) were profiled longitudinally using a gene panel and single-cell RNA sequencing. Residual tumor cells following tagraxofusp expressed lower levels of TXNRD1 that would reduce the efficacy of tagraxofusp. In support of this, enzymatic inhibition of TXNRD1 resulted in higher viability of CAL-1 BPDCN cells following tagraxofusp. Responders had either wild-type or missense TET2 mutations, while transient and non-responders had at least one truncating TET2 mutation. Examples of these mutations within the catalytic domain of TET2 were constructed and transduced into cells. Missense and truncating mutants displayed reduced sensitivities to hypomethylating agents and prolonged S-phase stasis. These results suggest that the levels of TXNRD1 interact with intrinsic TET2 truncating mutations within the bone marrow to modulate patient response to tagraxofusp.

The optimal first-line immunotherapy- or targeted therapy-based regimen for advanced gastric cancer (GC) and gastroesophageal junction cancer (GEJC) remains uncertain, largely because direct head-to-head comparisons are limited. We therefore conducted a network meta-analysis to compare the efficacy and safety of currently available first-line treatment strategies. PubMed, Embase, the Cochrane Library, and Web of Science were systematically searched from inception to January 10, 2026, for randomized controlled trials evaluating first-line immunotherapy- or targeted therapy-based regimens for advanced GC or GEJC. Overall survival (OS) and progression-free survival (PFS) were analyzed using hazard ratios (HRs), and dichotomous outcomes were analyzed using odds ratios (ORs), both with 95% credible intervals (CrIs). Risk of bias was assessed using the Cochrane RoB 2 tool. Bayesian network meta-analysis performs by R4.3.1. Nineteen randomized controlled trials involving 10,808 patients were included. No statistically significant differences were observed among treatment regimens for OS or PFS. Several immunotherapy- and targeted therapy-based regimens demonstrated improvements in short-term tumor response outcomes, including ORR and DCR; however, these improvements were not consistently associated with survival benefits. SUCRA-based ranking results suggested variability in probabilistic treatment ordering but should be interpreted as exploratory rather than definitive evidence of clinical superiority. Substantial clinical and methodological heterogeneity was observed across trials, including differences in biomarker status (PD-L1, HER2, CLDN18.2, FGFR2b), geographic regions, chemotherapy backbones, and subsequent treatment strategies. In safety analyses, EGFR-targeted agents showed relatively favorable profiles in selected outcomes. Although certain regimens were associated with improved short-term tumor responses, there is insufficient evidence to support definitive superiority in terms of long-term survival outcomes. Given biomarker heterogeneity, clinical variability, and limitations in network structure, these findings should be interpreted cautiously. Further biomarker-stratified and head-to-head randomized trials are warranted to better define optimal treatment strategies.

Entamoeba histolytica is a common enteric protozoan that sometimes transitions from a symbiont to a pathogen, causing intestinal amebiasis and extraintestinal abscesses in the host. The early-to-intermediate stages of intestinal amebiasis are characterized by an intense inflammatory response. Here, using the cecal infection model of C3H/HeNCrl mice, we performed single-cell RNA sequencing of cecal tissues and identified the prominent pro-inflammatory function of host macrophages in intestinal amebiasis. On the amebic cell surface, Igl is the intermediate subunit of galactose- and N-acetyl-D-galactosamine-inhibitable lectins, which contributes to parasite adherence. We proposed a potential mechanism whereby E. histolytica Igl diffuses along with amebic extracellular vesicles and contacts host macrophages, presumably binding to the TLR4 co-receptor MD2 through its C3 region and initiating the TLR4/MyD88/NF-&#x3ba;B inflammatory signaling pathway in host cells. Moreover, by inducing macrophage inflammation and cytokine production, E. histolytica appears to indirectly compromise intestinal epithelium integrity through the Igl protein. To our knowledge, this is the first report showing a host single-cell atlas in the field of amebiasis research. In response to the parasite invasion during intestinal amebiasis, our study yields additional clues elucidating the inflammatory formation and epithelial damage of gut mucosal immune system, and may contribute to the identification of potential drug targets for these amebas.