Search Results (4,827)

Mosquito-borne flaviviruses, including Dengue virus (DENV), Japanese encephalitis virus (JEV), West Nile virus (WNV), Yellow fever virus (YFV), and Zika virus (ZIKV), continue to present a significant threat to public health worldwide. In 2024, these viruses accounted for 11,717 reported cases in the United States and more than 7.6 million cases globally. As of early 2025, according to CDC data, 1830 cases of dengue had already been reported, with 1584 transmitted locally within the U.S. Despite the considerable burden that these diseases pose, no specific antiviral treatments exist. A very limited number of virus-specific vaccines have been licensed, such as those for YFV, JEV, and, with specific constraints, for DENV. To date, no pan-flavivirus vaccine is available. This review examines the potential of emerging vaccine platforms—particularly messenger RNA and virus-like particles—as promising tools in the pursuit of a broadly protective flavivirus vaccine. We analyze current strategies for inducing cross-neutralizing immune responses and discuss how these technologies could support the presentation of conserved quaternary epitope conformations, which are increasingly recognized as critical targets for establishing potent immune responses. We review key advances in virology, immune response, and immunogen delivery systems to highlight the potential for developing a pan-flavivirus vaccine. Full article

Conventional acoustic time-of-arrival (TOA) estimation in complex indoor environments is highly susceptible to multipath reflections and occlusions, resulting in unstable measurements and limited physical interpretability. This paper presents a smartphone-based indoor localization method built on vision-assisted acoustic channel modeling, and develops a fusion anchor integrating a pan–tilt–zoom (PTZ) camera and a near-ultrasonic signal transmitter to explicitly perceive indoor geometry, surface materials, and occlusion patterns. First, vision-derived priors are constructed on the anchor side based on line-of-sight reachability, orientation consistency, and directional risk, and are converted into soft anchor weights to suppress the impact of occlusion and pointing mismatch. Second, planar geometry and material cues reconstructed from camera images are used to generate probabilistic room impulse response (RIR) priors that cover the direct path and first-order reflections, where environmental uncertainty is mapped into path-dependent arrival-time variances and prior probabilities. Finally, under the RIR prior constraints, a path-wise posterior distribution is built from matched-filter outputs, and an adaptive fusion strategy is applied to switch between maximum a posteriori (MAP) and minimum mean square error (MMSE) estimators, yielding debiased TOA measurements with calibratable variances for downstream localization filters. Experiments in representative complex indoor scenarios demonstrate mean localization errors of 0.096 m and 0.115 m in static and dynamic tests, respectively, indicating improved accuracy and robustness over conventional TOA estimation. Full article

KRAS alterations are a hallmark of pancreatic ductal adenocarcinoma (PDAC) found in >90% of tumors. This review examines the historical evolution of the understanding of RAS and its central role in PDAC biology. We summarize the various downstream effectors, feedback loops, and resistance mechanisms that play a pivotal role in PDAC oncogenesis. Our review explores the early development of covalent inhibitors of KRAS G12C and efforts at specific inhibition of other codons and newer approaches of targeted protein degradation. We subsequently summarize the development of panRAS inhibitors and allosteric and switch-region targeting before focusing on rational therapeutic blockade of crosstalk and upstream signaling, with attention to synthetic lethality approaches transitioning from preclinical to early-phase in-human clinical trials. This review elaborates on ongoing KRAS-specific siRNA research and evolving KRAS-directed immunotherapies. We conclude by outlining the current KRAS clinical trial landscape and future areas of investigation. Full article

Pine needles are traditional herbal remedies used for centuries to treat various ailments, including rheumatism, bronchitis, burns, inflammation, and infections. This study aimed to evaluate the antioxidant, analgesic (peripheral and central), and wound-healing activities of Pinus pinaster (PPN) and Pinus halepensis (PAN) needles while identifying the bioactive compounds responsible for these effects. Phytochemical analysis revealed several phenolic compounds, including p-coumaroylquinic acid, quercetin, narcissin, and myricetin-3-O-glucoside. Both extracts showed strong antioxidant activity, with high total phenolic content (TPC: 384.84 ± 0.84 and 524.46 mg GAE/g DM for PPN and PAN, respectively) and flavonoid content (TFC: 109.44 ± 0.62 and 111.64 ± 0.62 mg QE/g DM, respectively). Peripheral analgesic activity, assessed using the acetic acid-induced writhing test, revealed that PAN (300 mg/kg) significantly reduced pain by 72.3%, while central analgesic effects, evaluated by the tail immersion test, were comparable to the reference drug for both extracts. In vivo wound-healing tests showed accelerated wound contraction and complete closure by day 21, indicating strong regenerative potential. Overall, this study demonstrates that PPN and PAN needle extracts possess significant antioxidant, analgesic, and wound-healing activities, supporting their traditional use and highlighting their potential as natural therapeutic agents for managing oxidative stress, pain, and skin injuries. Full article

The artistic exchange during Buddhism’s early transmission represents a vital field within Silk Road art studies. When Buddhist art first entered China during the Eastern Han Dynasty (25–220), many artistic elements originating from Indian and Central Asian traditions manifested via a highly fragmentary mode of dissemination. As a result, prior scholarship on Buddhist art in the Han Dynasty has predominantly focused on case studies of individual motifs such as Buddha images, lotus patterns, lions, and elephants. These studies form an essential foundation for the present research. This paper observes that Buddha images from the Han period were not always disseminated as isolated icons but were frequently closely associated with octagonal columns and arches/lintels. Tracing their origins reveals a connection to the “column–arch–Buddha” narrative motif found in the architectural art of Indian and Central Asian Buddhism. This motif extended eastward through the Western Regions (Xiyu 西域, present-day Xinjiang 新疆) and ultimately reached the core territories of the Han Empire, undergoing various transformations—including deconstruction, reassembly, and translation—in the process. Understanding these combinatory modes and their underlying intent is crucial for comprehending the essential nature of the early interaction and fusion between Buddhist art and Han Chinese civilization. Full article

Background/Objective: Early detection of metastatic progression remains a major challenge in precision oncology. Conventional radiological imaging cannot reliably identify micrometastatic disease. Although circulating tumor DNA is promising for minimal residual disease detection, organ-derived response biomarkers reflecting tissue adaptation to secreted factors remain unexplored. We hypothesized that integrating such biomarkers with global laboratory parameters would generate a synthetic variable with improved discrimination for de novo metastasis and mortality. Methods: This prospective observational pilot study enrolled 30 patients (median age 64.4 years; 56.7% female) with heterogeneous solid malignancies. Peripheral blood biomarkers responsive to tumor-secreted soluble factors (n = 11) were quantified using a multiplexed beads Luminex immunoassay. Global analytical parameters (n = 20) were derived from routine laboratory assessments. Hierarchical agglomerative clustering analysis generated two synthetic variables: Stigma (Ϛ) and Qoppa (Ϙ). Receiver operating characteristic curve analysis, Kaplan–Meier survival analysis, and Cox regression were used to evaluate the performance. Results: Qoppa demonstrated acceptable discriminatory performance for de novo metastasis (AUC = 0.78). For mortality prediction, performance varied by disease status (overall AUC = 0.78): superior in non-metastatic patients (AUC = 0.98) but negligible in those with baseline metastases. Kaplan–Meier analysis confirmed significant survival differences (p = 0.042 overall survival; p = 0.024 for metastasis-free survival in the non-metastatic subgroup). Differences in biomarker expression and clinical variables (stage, tumor burden, and metastatic burden) were observed between the high and low Qoppa strata. Conclusions: In this small heterogeneous pilot cohort, Qoppa provides a proof of concept that integrating organ-derived response biomarkers with routine laboratory parameters may capture clinically relevant signals for metastatic risk stratification in oncology patients. This composite parameter supports the generation of hypotheses for future biomarker-driven research and clinical test development. External validation in larger multicenter cohorts is required before clinical implementation. Full article

The incidence of tuberculosis disease (TBD) in New Brunswick (NB) is low but has been rising over the past decade. Analyzing these trends can help identify specific risk factors and transmission patterns to guide targeted public health strategies. This study aimed to provide a comprehensive and detailed characterization of TBD in NB by examining data from 1 January 2002, to 31 December 2024. All TB patients with Mycobacterium tuberculosis complex (MTBC) clinical isolates identified in NB healthcare facilities were eligible for inclusion in the study. We analyzed demographic, drug susceptibility, and 24-locus Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) data from 166 patients. Most MTBC isolates were pan-susceptible to first-line anti-tuberculosis drugs (90.9–98.1%), with 2.4% showing multidrug resistance. The MIRU-VNTR demonstrated a high discriminatory power of 0.9982 and a low clustering rate of 20.4%. Two samples from the same patient, collected seven years apart, showed different genetic profiles, suggesting that the second episode was a new infection. The most prevalent MTBC lineage was East African Indian (n = 23, 13%). This study provides early insights into TB trends in NB, including what may be the first recorded case of TB reinfection in NB. Our findings will help guide future TB research, policies, and public health interventions in the region. Full article

Background and Clinical Significance: Malaria remains a significant public health issue in Latin America, where Plasmodium vivax predominates but P. falciparum continues to circulate. Mixed-species infections are uncommon and can pose diagnostic challenges, particularly when parasite densities differ markedly, increasing the risk of underdetecting P. falciparum with conventional methods. Case report: We report a 9-year-old boy from an endemic area with a six-day febrile syndrome. Thick smear and peripheral blood film microscopy, complemented by rapid diagnostic tests for pan-Plasmodium and HRP2 antigens, confirmed a mixed infection with P. vivax (5500 parasites/µL) and P. falciparum (562 parasites/µL). The patient was hemodynamically stable, without severe malaria criteria, and laboratory values were within normal limits. Following confirmation of normal glucose-6-phosphate dehydrogenase activity, treatment with artemether–lumefantrine was initiated, followed by primaquine for hypnozoite eradication. Clinical evolution was favorable, with progressive defervescence, treatment tolerance, and documented parasite clearance. Conclusions: This case illustrates the risk of underestimating P. falciparum in mixed infections with disparate parasitemias and highlights the value of integrated diagnostic approaches in resource-limited endemic settings. It also underscores surveillance limitations that can misclassify mixed infections, potentially affecting epidemiological estimates and treatment strategies. Timely recognition and comprehensive diagnostic evaluation are essential to ensure appropriate antimalarial therapy, prevent complications, and inform public health interventions in regions where both species coexist. Full article

During the past decade, chatbots have been integrated into commercial platforms to facilitate second language acquisition (SLA) by providing opportunities for interactive conversations. However, SLA learner progress is limited by chatbots that lack the contextualization typically added by instructors to college and university courses. The present study focuses on a collaborative Digital Learning Incubator (DLI) project dedicated to creating and testing a chatbot with a physical form, or avatar chatbot, called Slabot (Second Language Acquisition Bot), in two upper-level university courses at the University of Tennessee, asynchronous online Spanish 331 (Introduction to Hispanic Culture), and in-person Spanish 434 (Hispanic Culture Through Film). Students in these two courses believe that their oral skills would benefit from more opportunities to speak in Spanish. To provide the students with more practice and instructors with a tool for assessing Spanish oral skills in online and in-person courses, the DLI project objective was to advance current avatar chatbot platforms by enabling Slabot to elicit student responses appropriate for evaluation according to the American Council on the Teaching of Foreign Languages (ACTFL) standards. An initial test of Slabot was conducted, and the results demonstrated the potential for Slabot to achieve the project objective. Full article

The clinical management of Pancreatic Neuroendocrine Neoplasms (Pan-NENs) is complicated by the disease’s intrinsic variability, which creates significant hurdles for accurate risk profiling and the standardization of treatment protocols. Recently, Artificial Intelligence (AI) has offered a promising avenue to address these challenges. By integrating and processing high-dimensional multimodal datasets (encompassing clinical history, radiomics, and pathology), these computational tools can refine survival forecasts and support the development of personalized medicine. However, the transition from experimental success to routine clinical use is currently obstructed by reliance on limited, retrospective cohorts that lack external validation, alongside unresolved concerns regarding algorithmic transparency and ethical governance. This review evaluates the current landscape of AI-driven prognostic modeling for Pan-NENs and critically examines the pathway towards their reliable integration into clinical practice. Full article

Extracellular vesicles (EVs) are emerging as key factors in maintaining cellular homeostasis, critical mediators of intercellular communication, potential biomarkers, and therapeutic tools. While small EVs have been extensively characterized, the molecular signatures of large EVs (including those generated during regulated cell death pathways) remain poorly defined. Here, we investigated the characteristics of large EVs released during apoptosis and pyroptosis by human monocytic cell lines (THP-1 and U937). Apoptosis was induced by staurosporine and blocked using the pan-caspase inhibitor Q-VD-OPh, whereas pyroptosis was triggered by LPS/nigericin and inhibited with a selective NLRP3 inhibitor. We found that both forms of regulated cell death markedly enhanced the release of large EVs. Both apoptotic and pyroptotic large EVs showed increased Annexin V binding and decreased CD9 expression compared with those released by healthy cells. Large EVs derived from apoptotic and pyroptotic cells exhibited distinct proteomic profiles. Pyroptotic large EVs carried interacting protein networks of RNA-binding proteins and chromatin-associated proteins many of which are known damage-associated molecular patterns or alarmins. In contrast, we found that a subpopulation of apoptotic large EVs was characterized by the presence of dsDNA, and active caspase-3/7. Together, our data shed light on the specific protein cargo of large EVs released by cells during apoptosis and pyroptosis. This study identifies candidate markers of large EVs released by dying cells and may enhance our understanding of the role of EVs in regulated cell death. Full article

Clarke provides a critical analysis of Pentecostalism as a tool for attaining the theological and political objectives of Pan-Africanism. However, this seems to suggest that, at least, African Pentecostals and African Pentecostal researchers may not be aware of the African Union’s (AU) Agenda 2013, or, at worst, they find no interest in engaging with Agenda 2063 if they are aware it exists. Using religion and politics—particularly Pentecostalism and politics—as a framework, this article notes that there are some points of convergence between their praxis and some of the seven aspirations of Agenda 2063. It addresses this phenomenon by using Mzondi’s Ubuntu Pentecostalism as a theological lens to reflect on how some of the actions and praxis of African Pentecostals relate to the African Union’s Agenda 2063. Ubuntu Pentecostalism holds to a holistic view of life and embraces William Seymour’s Pentecostalism, influenced by an African worldview, and either embraces or denounces ancestral veneration. The latter form of Ubuntu Pentecostalism is used in this article and placed alongside Pan-Africanism and African identity to provide a perspective on the third and fifth aspirations of the African Union’s Agenda 2063. The article further shows that (a) although African Pentecostals may not be aware of or do not bother to engage with the AU’s Agenda 2063, (b) their praxis and actions either support or contradict the third and fifth aspirations discussed in the article. Full article

Burkholderia pseudomallei complex and B. cepacia complex are two evolutionary distinct clades of pathogens causing human disease. Most vaccine efforts have focused on the former group largely due to their biothreat status and global disease burden. It has been proposed that a vaccine could be developed that simultaneously protects against both groups of Burkholderia by specifically targeting conserved antigens. Only a few studies have set out to identify which antigens may be optimal targets for such a vaccine. We have previously assessed the ability of three highly conserved B. pseudomallei antigens, namely OmpA1, OmpA2, and Pal, coupled to gold nanoparticle vaccines, to protect mice against a homotypic B. pseudomallei challenge. Here, we have expanded our study by demonstrating that antibodies to each of these proteins show varying levels of reactivity to homologues in B. cepacia complex, with OmpA2 antibodies exhibiting the highest cross-reactivity. Remarkably, some nanovaccine immunized mice, particularly those that received OmpA2, produced antibodies that bind Pseudomonas aeruginosa, which harbors distantly related homologous proteins. T cells elicited to Pal and OmpA2 responded to stimulation with B. cepacia complex-derived homologues. Our study supports incorporation of these antigens, particularly OmpA2, for the development of a pan-Burkholderia vaccine. Full article

Background: Stenotrophomonas maltophilia is an increasingly important multidrug-resistant opportunistic pathogen frequently isolated from clinical, environmental, and plant-associated niches. Despite its medical relevance, the global population structure, species-complex boundaries, and genomic determinants of antimicrobial resistance (AMR) and ecological adaptation remain poorly resolved, partly due to inconsistent annotations and fragmented genomic datasets. Methods: Approximately 2400 genome assemblies annotated as Stenotrophomonas maltophilia were available in the NCBI Assembly database at the time of query. After pre-download filtering to exclude metagenome-assembled genomes and atypical lineages, 1750 isolate genomes were retrieved and subjected to stringent quality control (completeness ≥90%, contamination ≤5%, ≤500 contigs, N50 ≥ 10 kb, and ≤1% ambiguous bases), yielding a final curated dataset of 1518 high-quality genomes used for downstream analyses. Genomes were assessed using CheckM, annotated with Prokka, and compared using average nucleotide identity (ANI), pan-genome analysis, core-genome phylogenomics, and functional annotation. AMR genes, mobile genetic elements (MGEs), and metadata (source, host, and geographic origin) were integrated to assess lineage-specific genomic features and ecological distributions. Results: ANI-based clustering resolved the S. maltophilia complex into multiple distinct genomospecies and revealed extensive misidentification of publicly deposited genomes. The pan-genome was highly open, reflecting strong genomic plasticity driven by accessory gene acquisition. Core-genome phylogeny resolved well-supported clades associated with clinical, environmental, and plant-related niches. Resistome profiling showed widespread intrinsic MDR determinants, with certain lineages enriched for efflux pumps, β-lactamases, and trimethoprim–sulfamethoxazole resistance markers. MGE analysis identified lineage-specific integrative conjugative elements, prophages, and transposases that correlated with source and geographic distribution. Conclusions: This large-scale analysis provides the most comprehensive genomic overview of the S. maltophilia complex to date. Our findings clarify species boundaries, highlight substantial taxonomic misannotation in public databases, and reveal lineage-specific AMR and mobilome patterns linked to ecological and clinical origins. The curated dataset and evolutionary insights generated here establish a foundation for global genomic surveillance, epidemiological tracking, and future studies on the evolution of antimicrobial resistance in S. maltophilia. Full article

Terpenes are major determinants of tea aroma, and terpene synthases (TPSs) catalyze key steps in terpenoid biosynthesis. To capture gene-family variation beyond a single reference, we performed a pan-genome–based analysis of TPS genes across nine Camellia genomes (three wild tea relatives and six cultivated Camellia sinensis accessions) and integrated pan-transcriptome profiling across eight tissues. We identified 381 TPS genes; wild species contained more TPSs than cultivated accessions (mean 58.3 vs. 34.3), suggesting a putative contraction. Phylogenetic analysis with Arabidopsis TPSs classified Camellia TPSs into five subfamilies, dominated by TPS-b (149) and TPS-a (140), whereas TPS-c was rare (8). Gene-structure and physicochemical analyses revealed marked subfamily divergence, with TPS-c showing highly conserved coding-region length. Orthology clustering assigned 355 TPSs to 19 orthogroups, including five core groups (190 genes, 53.5%) and 14 dispensable groups (165 genes, 46.5%); core/non-core status was significantly associated with subfamily composition. Tandem and proximal duplication contributed most to TPS expansion (29.4% and 29.1%), and all orthogroups exhibited copy-number variation, with pronounced lineage-specific expansions. Ka/Ks analyses indicated pervasive purifying selection (median 0.516) but heterogeneous constraints among subfamilies. Finally, cultivated tea showed higher TPS expression in most tissues, especially mature leaf and stem, and TPS-g displayed the broadest and strongest expression. Together, these results provide a pan-genome resource for Camellia TPSs and highlight how domestication, duplication, and CNV shape terpene-related genetic diversity. Full article