Search Results (554)

Acute Lymphoblastic Leukemia (ALL) is a highly prevalent hematological malignancy, especially in children, for whom precise and prompt subtype identification is essential to establish suitable treatment protocols. Current deep learning-based computer-aided diagnosis (CAD) methods for identifying ALL are hindered by numerous drawbacks, such as a dependence on solely spatial feature depictions, elevated feature dimensions, computationally extensive deep learning architectures, inadequate multi-layer feature utilization, and poor interpretability. This paper introduces LUMINA-Net, a custom, lightweight, and interpretable deep learning CAD for the automated identification and subtype diagnosis of ALL using microscopic blood smear pictures. LUMINA-Net makes four principal contributions: first, it integrates a self-attention module within a lightweight custom Convolution Neural Network (CNN) to effectively capture long-range spatial relationships across clinically pertinent cytological patterns while preserving a compact design. Second, it employs a Discrete Wavelet Transform (DWT)-based wavelet pooling layer that decreases feature dimensions by up to 96.875% while enhancing the obtained depictions with spatial-spectral information. Third, it utilizes a multi-layer feature fusion strategy that combines wavelet-pooled features from two deep layers with a third fully connected layer to create a discriminating multi-scale feature vector. Fourth, it incorporates Gradient-weighted Class Activation Mapping as a dedicated explainability process to furnish clinicians with apparent visual explanations for each classification decision. Withoit the need for image enhancement or segmentation preprocessing, LUMINA-Net outperforms the competing state-of-the-art methods on the same dataset, achieving a peak accuracy of 99.51%, specificity of 99.84%, and sensitivity of 99.51% on the publicly available Kaggle ALL dataset. This demonstrates that LUMINA-Net has the potential to be a dependable, effective, and clinically interpretable CAD tool for ALL diagnosis. Full article

This study presents HGRN2-based Flexible Dynamic Encoder Personal VAD (FDE-HGRN2), a recurrent framework for personal voice activity detection (PVAD). Building on the original LSTM-based FDE-RNN backbone, we replace all recurrent modules with the recently introduced HGRN2 gated linear RNN and adopt a cosine-annealing learning rate schedule to improve both detection accuracy and efficiency. HGRN2 uses gated linear recurrence with non-parametric state expansion, enlarging the recurrent state without increasing the number of trainable parameters and enabling more expressive long-range temporal modeling than conventional LSTMs. We evaluate FDE-HGRN2 on a LibriSpeech-derived PVAD benchmark, where multi-speaker mixtures are constructed by concatenating one to three speakers per utterance and randomly designating a target speaker, following established PVAD data construction practices to ensure direct comparability with prior work. The system uses 40-dimensional Mel-filterbank features as acoustic inputs and conditions the detector on 256-dimensional d-vector embeddings extracted from a pretrained speaker verification network. Experimental results show that FDE-HGRN2 consistently outperforms the original FDE-RNN baseline and several state-of-the-art PVAD models in terms of mean Average Precision and frame-level accuracy, while reducing the parameter count of the recurrent backbone by roughly 15% and yielding substantially smaller models than many competing systems. These findings indicate that HGRN2 provides a more temporally expressive and parameter-efficient alternative to LSTM for PVAD, offering a favorable accuracy–efficiency trade-off for real-world, deployment-oriented personalized speech interfaces. Full article

The northward expansion of Dirofilaria spp. is a current medical and veterinary concern. However, it is unclear how far north the parasite has spread in Western Siberia and what species of mosquito can carry and transmit it. This study examined Dirofilaria spp. infection in Aedes mosquitoes in the taiga zone of the Irtysh Basin. The mosquito species were identified based on morphology, and Dirofilaria spp. were identified using PCR. Of the 13 habitats surveyed, 24 of 2205 mosquito samples were infected with D. repens and 1 with Dirofilaria sp. The highest infection rate (~7.6) was recorded in Tobolsk, Tyumen region, at 58.4° N. Mosquito infection was recorded as far north as 61° N in Khanty-Mansiysk. The presence of the infective L3 stage of the parasite was recorded up to 60° N in Bobrovsky. Nine species of mosquitoes were found to be infected with D. repens: Aedes rossicus, Aedes behningi, Aedes cantans, Aedes communis, Aedes cyprius, Aedes euedes, Aedes excrucians, Aedes flavescens, and Aedes sticticus. Two of these species, Ae. behningi and Ae. communis, were competent vectors of the parasite. Thus, D. repens has successfully adapted to the Aedes mosquito in the taiga zone of Siberia. Full article

Dirofilaria repens is the leading cause of subcutaneous (dogs) and subcutaneous/ocular dirofilariosis (humans) in the Old World. Despite its rapid geographical spread, driven by climate change, the emergence of new invasive vectors (Aedes albopictus) and growing interest in its study due to the emergence of new cases in areas previously free of the parasite, amongst other factors, scientific research into this pathogen remains limited. This study provides the first longitudinal bibliometric analysis of global research on D. repens (1955–2025). Data from Web of Science and Scopus were processed using PRISMA and RAMIBS protocols, resulting in a normalized corpus of 624 documents analyzed via science mapping techniques. The field exhibits a sustained annual growth rate of 3.79%, transitioning into an exponential expansion phase in 2011. While Italy retains historical leadership, spatial analysis confirms a research displacement towards Central and Eastern Europe (Germany, Poland). Thematic evolution reveals a structural shift from isolated clinical case reports to a multidisciplinary ecosystem dominated by molecular epidemiology, vector competence, and surveillance. Dirofilaria repens has gone from being a minor and neglected issue to having a significant number of reports and studies subject to interest in addressing the disease that results from its infection in different hosts. However, the intellectual structure exposes an operational fragmentation between clinical medicine and medical entomology. Future research must overcome national silos and integrate reservoir management with vector control, transforming the current reactive approach into a predictive preventive system aligned with the One Health framework. Full article

Background/Objectives: The F3 peptide, a tumor-homing peptide known to bind cell-surface nucleolin, is frequently employed as a targeting vector in cancer research. However, the impact of the modification site on its cellular binding properties has not been investigated yet. In this work, we aimed to design an improved F3-based radioconjugate by identifying the optimal conjugation site and establishing a protocol for its biological evaluation in vitro. To achieve this, we compared F3 peptide derivatives modified at their N- or C-termini with DOTA for complexation of indium-111 (¹¹¹In) for SPECT or Auger electron therapy or a fluorophore (FITC) for optical imaging. Methods: N-and C-terminal DOTA-modified F3 peptides were radiolabeled with indium-111 and compared for their in vitro stability in different physiologically relevant media. Suitable nucleolin-positive cell lines for further in vitro studies were identified by confocal microscopy of a FITC-labeled F3 peptide derivative. The radioconjugates were then investigated on MDA-MB-231 (breast cancer) and PC-3 (prostate cancer) cells for nucleolin-specific cell binding and uptake, and several parameters of the in vitro assays were varied to establish a suitable protocol. Results: In general, in vitro assays with F3 peptide conjugates are challenging, as the outcome depends on a number of experimental parameters, leading, in some cases, to varying results. In particular, the presence of Ca²⁺ and Mg²⁺ had a decisive impact on the results, likely because the metal ions compete with the binding of F3 conjugates to nucleolin. The C-terminal modified, ¹¹¹In-labeled F3 radioconjugate performed better than the N-terminal modified analog. While several parameters of the in vitro experiments were optimized, the overall cell uptake in vitro of radioactivity was still low (<2% of applied radioactivity). Conclusions: A standardized in vitro protocol for evaluating F3 peptide conjugates on cancer cells was established, revealing that the C-terminus is the preferred site for modification. Because the cellular uptake of the radiotracer was shown to likely not be sufficient for radiotracer development, further studies on the optimization of the F3 peptide conjugates, including structural modifications, are required. Full article

Aedes aegypti is a primary vector for globally significant arboviruses such as dengue virus (DENV). The mosquito’s metavirome, particularly its insect-specific virus (ISV) component, is recognized as a key modulator of arboviral transmission. However, the natural ecology of these interactions in populations remains poorly understood. This study presents the first comparative analysis of the metavirome in wild-caught A. aegypti from Vietnam based on natural DENV infection status. Metaviromic analysis was performed on 69 DENV-positive pools from six central provinces. The results obtained were compared with previously obtained metaviromic data from 7 DENV-negative pools (from the same region). Analysis suggests the presence of a stable ‘core metavirome’ of 11 ISVs present in both groups. Interestingly, six ISVs were detected only in DENV-negative mosquitoes, which may suggest potential antagonistic interactions requiring further investigation. Conversely, five ISVs were found only in DENV-positive pools, including Aedes partiti-like virus 1 and Aedes anphevirus. The latter may suggest possible synergistic relationships that facilitate arboviral replication. Phylogenetic analysis of prevalent ISVs, such as Phasi Charoen-like phasivirus (PCLV) and Chaq-like virus, revealed patterns of both local circulation and genetic diversity. The findings describe distinct ISV profiles associated with DENV infection in a natural setting, providing a data-driven foundation for hypothesizing specific virus–virus interactions. The data underscores the complexity of the mosquito metavirome. Here, we identified several candidate ISVs for future experimental studies aimed at understanding potential functional impact on arboviral vector competence. Full article

The overuse of chemical insecticides highlights the urgent need for novel vector control strategies. Insect-specific viruses (ISVs), such as the cell-fusing agent virus (CFAV), have shown potential to block arbovirus transmission by inhibiting viral replication in mosquitoes. However, the effects of CFAV beyond its natural host, Aedes aegypti, remain largely unexplored. In this study, we established a CFAV infection model in Aedes albopictus, a major vector for Zika virus (ZIKV), via intrathoracic injection. Stable infection was achieved, with viral loads reaching up to 10⁷ copies per mosquito by day 10 post-injection. Nevertheless, high post-injection mortality (median survival: 3 days) was observed, which we attribute primarily to mechanical injury. No evidence of vertical transmission of CFAV was detected in Ae. albopictus. Co-injection of CFAV and ZIKV did not significantly affect ZIKV replication in this species. In contrast, in Ae. aegypti pre-infected with CFAV followed by oral ZIKV challenge, CFAV significantly reduced ZIKV infection rates in the ovaries at day 4 and viral loads in salivary glands at day 10. These findings demonstrate that while CFAV can productively infect Ae. albopictus, it does not undergo vertical transmission in this species, and has no inhibitory effect on ZIKV under the co-infection conditions tested. This study underscores challenges associated with using single ISVs such as CFAV for arbovirus control and highlights the complex, bidirectional role of multiple ISV co-infections. While exploring multi-ISV combinations may offer a potential strategy to enhance antiviral efficacy, their net effect—whether suppression or enhancement of arboviruses—warrants careful investigation. Full article

Background/Objectives: Eliciting robust immune responses against the hepatitis B virus (HBV) through therapeutic vaccination holds promise for curing chronic hepatitis B. We previously developed the heterologous protein prime/viral vector boost clinical vaccine candidate, TherVacB. Here, we evaluated a replication-competent chimeric vesicular stomatitis virus vector (VSV-GP) as an alternative viral vector boost vaccine. Methods: A recombinant VSV-GP vector co-expressing HBV surface and core antigens (VSV-GP-HBs/c) was generated and characterized for antigen expression. Its immunogenicity, antiviral efficacy, and durability were assessed in HBV-naïve and HBV-carrier mice, using protein primed, viral vector-primed, and multi-viral vector boost regimens. Results: VSV-GP-HBs/c efficiently expressed both HBV antigens in vitro. A single immunization with VSV-GP-HBs/c induced only weak HBV-specific immune responses in vivo. Replacing protein priming with VSV-GP-HBs/c resulted in modest immune activation and limited antiviral effects in HBV-carrier mice. In contrast, substituting the modified vaccinia virus Ankara (MVA)-HBs/c boost in the TherVacB regimen with VSV-GP-HBs/c elicited robust HBV-specific antibody responses and strong CD4 and CD8 T-cell immunity, assessed by intracellular IFN-γ staining after peptide stimulation. This regimen achieved a substantial reduction in serum HBsAg levels, numbers of HBV-positive hepatocytes, and intrahepatic HBV-DNA, with antiviral efficacy comparable to that of the classical TherVacB regimen. Notably, a second viral vector boost did not enhance HBV-specific immunity or antiviral efficacy; instead, it promoted dominant vector-specific CD8 T-cell responses. Long-term analyses performed 10 weeks after the last vaccination further demonstrated that a single protein-prime/VSV-GP-HBs/c boost was sufficient to achieve sustained antiviral control. Conclusions: These findings identify VSV-GP-HBs/c as an effective boost vector for therapeutic hepatitis B vaccination and establish protein priming followed by a single viral vector boost as an optimal strategy for sustained antiviral immunity. Full article

Background/Objectives: Recombinant adeno-associated virus (rAAV) has become a leading vector in gene therapy. However, manufacturing limitations may result in replication-competent AAV (rcAAV) contamination of clinical rAAV products, posing safety risks. Rigorous testing is therefore essential, and the use of accurately calibrated rcAAV reference standard materials is critical for ensuring assay stability and reliability. A disadvantage of the widely used Tissue Culture Infectious Dose 50 (TCID₅₀) assay is its high variability. This study introduces an optimized TCID₅₀ assay for the precise quantification of infectious rcAAV particles. Methods: We developed a TCID₅₀ assay tailored to rep2-based rcAAV, optimizing key aspects such as viral infection conditions, qPCR reaction systems, and standard curve preparation. We employed an innovative strategy to prepare the standard curve using serial dilutions of rcAAV in cell lysate, ensuring alignment with the test sample matrices. Results: The rcAAV-derived standard curve demonstrated exceptional linearity (R² > 0.99), sensitivity (LOQ ≈ 38 copies), and reproducibility, enabling robust endpoint qPCR analysis. The optimized assay significantly improved the precision of the TCID₅₀ assay, as an inter-assay coefficient of variation (CV) of 11.4% was achieved. Conclusions: This refined TCID₅₀ assay is a reliable method for calibrating infectious titers of rcAAV reference standard materials, thereby enabling the standardization of rcAAV testing. Full article

Theileria haneyi, a recently discovered tick-borne hemoparasite infecting equids globally, has significant implications for equine health. Although it is closely related to T. equi (sharing 23% genomic divergence), it establishes an asymptomatic carrier state in persistently infected horses, creating a silent transmission reservoir. Its discovery and unique genetics justify its classification as a new taxon. A critical diagnostic challenge is that the lack of the ema-1 gene in T. haneyi prevents its detection by the standard T. equi cELISA, emphasizing the need for species-specific tools. Although species-specific PCR assays, including PCR and qPCR targeting genes like chr1sco or ema-11, respectively, and an indirect ELISA targeting the EMA-11 recombinant protein, have been developed, global genetic variations may limit their serological utility. Therapeutically, T. haneyi exhibits resistance to the key antiparasitic drug, imidocarb dipropionate (ID), and interferes with the clearance of co-infecting T. equi. Major knowledge gaps persist, particularly regarding the identification of its competent vector. The current work presents an overview of T. haneyi virulence, transmission, diagnostics, and therapeutic gaps while pinpointing the deficits in current information necessary for advancing our understanding of the parasite’s biology. Finally, the review discusses and recommends further studies to develop effective control and surveillance strategies for T. haneyi infection. Full article

As a core pastoral region of the Qinghai–Tibet Plateau, Qinghai Province faces substantial threats to livestock production from tick-borne diseases. This study aimed to investigate the prevalence of six bacterial pathogens in dominant tick species from Qinghai Province, to provide baseline epidemiological data for local tick-borne disease surveillance. A total of 1025 questing ticks were collected from key pastoral regions of Qinghai Province during April to May in 2024 and 2025. All ticks were morphologically identified as belonging to 1 family (Ixodidae), 2 genera, and 4 species. Dermacentor nuttalli was the dominant species with a relative dominance of 66.83% (685/1025, 95% CI: 63.92–69.61%), followed by Haemaphysalis qinghaiensis at 30.83% (316/1025, 95% CI: 28.11–33.69%), Dermacentor silvarum at 1.95% (20/1025, 95% CI: 1.27–2.98%), and Dermacentor niveus at 0.39% (4/1025, 95% CI: 0.15–1.01%). PCR detection was performed for six target pathogens, with an overall Brucella spp. DNA detection rate of 0.78% (8/1025, 95% CI: 0.40–1.53%) and an overall Rickettsia spp. detection rate of 16.29% (167/1025, 95% CI: 14.16–18.67%). Statistical analysis showed that the prevalence of Brucella spp. and Rickettsia spp. differed significantly between the two dominant tick species (Fisher’s exact test/χ² test, all p < 0.001). No Brucella or Rickettsia pathogens were detected in D. silvarum and D. niveus. Notably, detection of Brucella spp. DNA does not confirm the presence of viable bacteria or tick vector competence. This study fills the regional data gap of tick-borne pathogens in Qinghai, and provides reference for the prevention and control of local tick-borne zoonotic diseases. Full article

Background: Zika virus (ZIKV) is a mosquito-borne flavivirus associated with severe neurological disease, including congenital Zika syndrome (CZS) following utero infection and Guillain–Barré syndrome in adults. The 2015–2016 epidemic in the Americas highlighted the profound maternal and neonatal consequences of ZIKV infection. Although reported transmission has declined, ongoing circulation of competent vectors and population susceptibility sustain a substantial risk of future outbreaks, underscoring the need for effective vaccines. Methods: We developed a recombinant Modified Vaccinia Ankara (MVA)-based vaccine candidate expressing the ZIKV pre-membrane (prM) and envelope (E) proteins and evaluated its immunogenicity and protective efficacy in interferon receptor-deficient AG129 mice. Results: Vaccination induced strong humoral and cellular immune responses and conferred significant protection against viral replication in key target organs, including the brain and testes, following ZIKV challenge. Conclusions: These preclinical findings support further development of this MVA-based ZIKV vaccine as a promising strategy to prevent ZIKV infection and its associated neurological complications. Full article

Trypanosoma vivax is a hemoprotozoan parasite of major veterinary importance affecting domestic ungulates in Africa and the Americas. While traditionally addressed within cattle-centered paradigms, accumulating evidence indicates that water buffaloes (Bubalus bubalis) are both clinically susceptible and epidemiologically significant hosts. This structured narrative review provides a host-centered synthesis of global evidence on T. vivax infection in buffaloes, integrating pathogenesis, transmission biology, epidemiology, diagnostics, chemotherapy, and integrated control. The analysis encompasses literature from 2000 to 2025 and incorporates seminal experimental studies published prior to 2000 that established buffalo susceptibility and reservoir competence. Evidence from cyclical (tsetse-mediated) and mechanical transmission systems is comparatively interpreted to clarify host–parasite dynamics. The Amazon biome is discussed as a model system for high-density buffalo production under mechanical vector pressure, offering case-based contextualization without geographic restriction. Particular attention is given to immunopathological mechanisms, chronic low-parasitemia carriage, diagnostic sensitivity in subclinical infections, emerging trypanocide resistance, and ecological constraints on vector control. Controversies and buffalo-specific knowledge gaps are highlighted throughout. By adopting a buffalo-centered analytical framework, this review supports translational diagnostics, targeted surveillance, and sustainable control strategies for trypanosomiasis in tropical livestock systems. Full article

Rice blast disease is one of the most contagious and destructive diseases affecting rice, posing a serious threat to global rice production and the agricultural economy. To enable accurate early detection under field conditions, this study proposes an integrated feature sorting algorithm (IFSA). The algorithm integrates five spectral feature selection methods—partial least squares, successive projections algorithm (SPA), principal component analysis loading (PCA-Loading), genetic algorithm (GA), and random forest (RF)—and employs the Borda count method for comprehensive feature ranking and selection. Field experiments were conducted in Haicheng, Anshan, Liaoning Province, China, using the rice cultivar Yanfeng 47. A total of 4893 hyperspectral samples were collected under natural field conditions. The results demonstrate that IFSA effectively identifies key spectral wavelengths for the early diagnosis of rice blast disease, achieving significantly higher detection accuracy than conventional single-method dimensionality reduction approaches. Based on the IFSA-selected wavelengths, an early detection model (Inception-CBAM) was further developed by integrating a multi-channel convolutional neural network with a convolutional block attention module, thereby enhancing the extraction and recognition of early disease-related features. Compared with six baseline models (InceptionV4, ResNet, BiGRU, RF, support vector machine, and extreme learning machine), Inception-CBAM achieved an overall accuracy of 95.44 ± 0.50% and a Kappa coefficient of 93.92 ± 0.67% for early rice blast disease detection, outperforming all competing methods. This study confirms the effectiveness of IFSA for hyperspectral feature selection and demonstrates that the proposed Inception-CBAM model provides strong capability for early disease detection. Nevertheless, the data were collected from a single cultivar and a single region; therefore, the model’s generalization performance across broader environments requires further improvement. Future work will extend the evaluation to multi-cultivar and multi-region scenarios to facilitate practical deployment for real-time field diagnosis. Full article

Pain recognition based on multimodal physiological signals remains a challenge, not only because of the limited training data, but also due to the varying responses of individuals. In this article, we present a randomized modality mixing technique (Modmix) for multimodal data augmentation and a patchwise radial basis function (RBF) network designed to improve robustness in limited and highly heterogeneous data. Modmix generates new samples by randomly swapping modalities between existing data points, creating new data in a very simple but effective way. The RBF patch network divides the input into randomly selected, overlapping patches that capture local similarities between modalities. Each patch network is trained end-to-end using stochastic gradient descent. Moreover, the model’s performance is further improved by using multiple independently trained networks and combining them into a single decision. Experiments with the two different pain datasets X-ITE and BioVid were performed under limited training data conditions, where only approximately 30% of the original datasets were used for training. With both datasets the RBF patch network achieved significant improvements for a subset of subjects, resulting in a similar or even slightly better mean accuracy compared to competing related models such as random forest and support vector machine. Full article