Search Results (30)

The southern pudu (Pudu puda) faces significant threats from anthropogenic activities and infectious diseases. Using whole-genome sequencing (WGS) and forensic microbiology research, we describe a triple bacterial co-infection in a southern pudu impacted by wildfire disasters. The deer presented infected burn wounds on the extremities and dog bite wounds in the lumbosacral region, from which a multidrug-resistant CTX-M-1-producing Escherichia coli sequence type (ST) ST224 and a Klebsiella oxytoca ST145 were isolated, respectively. The patient died 13 days after admission in a wildlife rehabilitation center. During the necropsy, a sample from intracardiac blood was collected, and WGS analyses confirmed systemic dissemination of an E. coli ST224 clone. The broad virulome (adhesins, invasins, toxins, and immune evasion genes) and resistome against beta-lactams (bla_CTX-M-1), aminoglycosides [aac(3)-IId, aph(3′)-Ia, aph(3″)-Ib, aph(6)-Id], macrolides [mph(A)], sulfonamides (sul2), trimethoprim (dfrA17), and fluoroquinolones (gyrA and parC mutations) of E. coli ST224 contributed to the treatment failure and death of the wild animal. Additionally, an oval nodule was identified in the abdominal cavity caused by Acinetobacter baumannii ST1365, the first WGS-confirmed report in wildlife. This study highlights the value of applying forensic microbiology and WGS to investigate and understand One Health pathogens threatening wildlife impacted by natural and anthropogenic disasters. Full article

Background/Objective: Programmed cell death ligand-1 (PD-L1), which is overexpressed in certain tumors, inhibits the body’s natural immune response by providing an “off” signal that enables cancer cells to evade the immune system. It has been demonstrated that [¹⁷⁷Lu]Lu-DOTA-iPD-L1 (PD-L1 inhibitor cyclic peptide) promotes immune responses. This study aimed to synthesize and evaluate [¹⁸F]AlF-NOTA-iPD-L1 as a novel radiotracer for PD-L1 positron emission tomography (PET) imaging and as a potential theranostic pair for [¹⁷⁷Lu]Lu-DOTA-iPD-L1. Methods: The NOTA-iPD-L1 peptide conjugate was synthesized and characterized by U.V.-vis, I.R.-FT, and UPLC-mass spectroscopies. Radiolabeling was performed using [¹⁸F]AlF as the precursor, and the radiochemical purity (HPLC), partition coefficient, and serum stability were assessed. Cellular uptake and internalization (in 4T1 triple-negative breast cancer cells), binding competition, immunofluorescence, and Western blot assays were applied for the radiotracer in vitro characterization. Biodistribution in mice bearing 4T1 tumors was performed, and molecular imaging (Cerenkov images) of [¹⁸F]AlF-NOTA-iPD-L1 and [¹⁷⁷Lu]Lu-DOTA-iPD-L1 in the same mouse was obtained. Results: [¹⁸F]AlF-NOTA-iPD-L1 was prepared with a radiochemical purity greater than 97%, and it demonstrated high in vitro and in vivo stability, as well as specific recognition by the PD-L1 protein (IC₅₀ = 9.27 ± 2.69 nM). Biodistribution studies indicated a tumor uptake of 6.4% ± 0.9% ID/g at 1-hour post-administration, and Cerenkov images showed a high tumor uptake of both [¹⁸F]AlF-NOTA-iPD-L1 and ¹⁷⁷Lu-iPD-L1 in the same mouse. Conclusions: These results warrant further studies to evaluate the clinical usefulness of [¹⁸F]AlF-NOTA-iPD-L1/[¹⁷⁷Lu]Lu-DOTA-iPD-L1 as a radiotheranostic pair in combination with anti-PD-L1/PD1 immunotherapy. Full article

Purpose: This article aims to harmonize the current data from the literature, describe baseline severity, and discuss potential treatment considerations for cases of triple infection. Patients and Methods: We undertook a retrospective, observational study on 1244 patients with viral hepatitis study subgroups: chronic replicative hepatitis with HCV—679 patients, HBV—98 patients, HBV/HCV—25 patients, HBV/HDV—14 patients, and 2 patients with triple-infection (HBV, HCV, and HDV), hospitalized in the Second Department of “Sf. Cuv. Parascheva” Infectious Diseases Clinical Hospital of Galați, Romania, between 1 April 2017 and 1 March 2025. Results: Comparative analysis of biochemical parameters and liver fibrosis—at the initial testing—i.e., at the beginning of the specific antiviral therapy—with direct-acting antivirals on HCV (DAAs) or nucleos(t)ide analogues (NUCs): Entecavir (ETV) or Tenofovir Disoproxyl fumarate (TDF), for HBV, Bulevirtide (BLV) for HDV—revealed clinical forms with higher severity in the case of triple and double infections, in comparison to individuals who have had only one hepatotropic virus infection. Conclusions: Compared to patients with a single hepatotropic viral infection, those with a double or triple infection had more severe hepatic damage. Concomitant therapy with Bulevirtide, DAAs, and NUCs is possible and the therapeutic results from clinical studies, with single-infection patients showing great potential for improving the prognosis of these patients. Full article

Accurate fish population estimation is crucial for fisheries management, ecological monitoring, and aquaculture optimization. Traditional manual counting methods are labor-intensive and error-prone, while existing automated approaches struggle with occlusions, small-object detection, and identity switches. To address these challenges, this paper proposes an improved fish counting framework integrating YOLOv8-DT for detection and Byte-OCSORT for tracking. YOLOv8-DT incorporates the Deformable Large Kernel Attention Cross Stage Partial (DLKA CSP) module for adaptive receptive field adjustment and the Triple Detail Feature Infusion (TDFI) module for enhanced multi-scale feature fusion, improving small-object detection and occlusion robustness. Byte-OCSORT extends OC-SORT by integrating ByteTrack’s two-stage matching and a Class-Aware Cost Matrix (CCM), reducing ID switches and improving multi-species tracking stability. Experimental results on real-world underwater datasets demonstrate that YOLOv8-DT achieves a mAP₅₀ of 0.971 and mAP_50:95 of 0.742, while Byte-OCSORT reaches a MOTA of 72.3 and IDF1 of 69.4, significantly outperforming existing methods, confirming the effectiveness of the proposed framework for robust and accurate fish counting in complex aquatic environments. Full article

Background/Objectives: In 2022, approximately 2.3 million women were diagnosed with breast cancer worldwide, resulting in 670,000 deaths, which accounted for 6.9% of all cancer-related deaths. In the United States, 1 in 8 women will be diagnosed with breast cancer during their lifetime. It was estimated that 2024 would identify about 310,720 women and 2800 men diagnosed with invasive breast cancer. The future global burden of breast cancer is projected to rise to over 3 million new cases and 1 million deaths by 2040. Approximately 20% of breast cancer diagnoses are triple-negative breast cancer (TNBC), a type of cancer that lacks receptors for estrogen (ER-negative), progesterone (PR-negative), and human epidermal growth factor receptor 2 (HER2/neu-negative). Consequently, TNBC does not respond to hormonal or targeted therapies, making it challenging to treat due to its rapid growth, metastasis, and high recurrence rate within the first three years of therapy. Alternative chemotherapies are needed to address this problem. A pharmacological dose of vitamin C (high-dose VC) has been identified as a potential treatment for some cancer cells. The present study aimed to evaluate whether VC has a therapeutic effect on TNBC, using MDA-MB-231 cells as the model. Additionally, VC’s effects were trialed on other cancer cells such as MCF7 and on non-cancerous kidney HEK 293 and lung CCL205 cells. Methods: The MTT assay, Hoechst 33342 staining, nuclear-ID red/green staining, Rhodamine 123 staining, and Western blot analysis were employed to test the hypothesis that a pharmacological dose of VC can kill TNBC cells. Results: The upregulation of Apaf-1 and caspases -7, -8, and -9, the inhibition of matrix metalloproteinases (MMP-2 and MMP-9), a reduction in cell cycle protein expression, and the enhancement of tumor suppressor proteins such as p53 and p21 indicate that a pharmacological dose of VC has promising anti-cancer properties in the treatment of breast cancers. Conclusions: Pharmacological dose of VC exerts significant anti-cancer effects in MDA-MB-231 cells by promoting apoptosis, inhibiting metastasis, disrupting cell cycle progression, and enhancing tumor suppressor activity. Full article

Despite the availability of excellent HPV-specific vaccines, HPV-related conditions and, notably, their related neoplastic diseases are expected to impact human health for many years to come. Polyphenols and flavonoids are a large class of natural products, credited with a wide range of pharmacological properties including antineoplastic activity. However, the currently available data depict a rather heterogeneous and sometimes contradictory landscape, and no univocal conclusions can be drawn. To shed light on such a controversial issue, a restricted list of promising polyphenols were evaluated for their antineoplastic activity on HPV-transformed cells. Among them, Kaempferol, Galangin, and Luteolin proved to have distinct anti-clonal activity with ID₅₀ values, respectively, of 1.25, 6.25, and 3.0 microMolar, and three other compounds, namely, Chrysin, Quercetin, and Apigenin, showed fair although less intense activity with ID values, respectively, of 25.0, 40, and 25 microMolar. Interestingly, a distinct anti-proliferative effect could also be suggested for Kaempferol, Luteolin, and Apigenine. Cooperative anti-clonal effects could be suggested for binary and ternary compositions made of Kaepferol, Galangin, and Luteolin once combined at concentrations ranging from 2 to 8 microMolar. At these concentrations, the single components and the triple combination induced distinct cell cycle modulation associated with marked restoration of the p53 and p21Cip1/Waf1 levels, consistent with the disruption of the E6/E6AP interaction whose continuous activity is necessary for both the induction and maintenance of the viral-induced neoplastic phenotype. Full article

Single-phase high entropy alloys (HEAs) exhibit limited mechanical properties while dual-phase and multi-phase HEAs offer better strength, toughness, and stability. In this paper, the as-cast Al_xFe_1.5CoNiC_0.12 HEAs with triple-phase dendritic composite structure is studied, and the influence of the composite structure on the mechanical properties is discussed. The interdendrite (ID) of this structure is composed of a uniformly distributed high-density ordered face-centered cubic structure (L1₂) precipitate phase and face-centered cubic (FCC) matrix, while the dendrite (DR) consists of an ordered body-centered cubic (B2) single-phase. The high density L1₂ precipitate phase leads to a higher hardness in the FCC+L1₂ dual-phase region compared to the B2 single-phase region. The decrease in Al content can greatly improve mechanical performance. The improvement was attributed to the higher volume fraction of the ID and the smaller particle size of the precipitates. The L1₂ phase nano-precipitates exhibit minimal lattice mismatch with the FCC matrix, thereby significantly enhancing the stability of the alloy at the nanoscale. This stability is reflected in the fracture morphology. Modulating the triple-phase dendritic composite structure effectively improves the mechanical properties of the alloy. Full article

We consider the concept of fuzzy $\mathcal{H}$-quasi-contraction ($\mathcal{F}\mathcal{H}$-$\mathcal{Q}\mathcal{C}$ for short) initiated by Ćirić in tripled fuzzy metric spaces ($\mathcal{T}$-$\mathcal{F}\mathcal{M}\mathcal{S}$s for short) and present a new fixed point theorem ($\mathcal{F}\mathcal{P}\mathcal{T}$ for short) for $\mathcal{F}\mathcal{H}$-$\mathcal{Q}\mathcal{C}$ in complete $\mathcal{T}$-$\mathcal{F}\mathcal{M}\mathcal{S}$s. As an application, we prove the corresponding results of the previous literature in setting fuzzy metric spaces ($\mathcal{F}\mathcal{M}\mathcal{S}$s for short). Moreover, we obtain theorems of sufficient and necessary conditions which can be used to demonstrate the existence of fixed points. In addition, we construct relevant examples to illustrate the corresponding results. Finally, we show the existence and uniqueness of solutions for integral equations by applying our new results. Full article

Selenium, zinc, copper, and manganese are essential components of antioxidant enzymes involved in the elimination of reactive oxygen species (ROS). Given that cancer cells produce high levels of ROS and the accumulation of ROS can lead to cell death, cancer cells may be susceptible to strategies that reduce ROS elimination. In this work, we prepared several artificial diets that contained normal carbohydrate, protein, and lipid levels but lacked selenium, zinc, copper, or manganese. The anticancer activity of these diets was examined in a metastatic ovarian cancer model, established by injecting ID8 Trp53^−/− murine ovarian cancer cells into the peritoneal cavity of C57BL/6JRj mice. Treatments started 15 days later and consisted of replacing a normal diet with one of the artificial diets for several weeks. A significant improvement in mice survival was observed when the normal diet was replaced with the selenium-free diet. Diets lacking zinc, copper, or manganese showed no significant impact on mice survival. All diets were very well tolerated. The anticancer efficacy of a diet lacking selenium was confirmed in mice with metastatic colon cancer and in mice with metastatic triple-negative breast cancer. These results suggest that diets lacking selenium hold potential for the treatment of metastatic cancers. Full article

Multiple myeloma (MM) is an incurable plasma cell malignancy. In the context of the current standard of care therapies in Canada, outcomes among patients with relapsed/refractory multiple myeloma (RRMM), particularly those with triple-class (or more) refractory disease remain poor. Immunotherapies have significantly changed the treatment landscape of MM. Since 2021, two BCMA-targeting CAR T-cell therapy products have been approved for RRMM—namely Idecabtagene vicleucel (Ide-cel) (ABECMA^®) and Ciltacabtagene autoleucel (Cilta-cel) (CARVYKTI^®), both of which are available in the US and Europe. Although they have shown unprecedented efficacy in RRMM, their clinical and logistical limitations must be acknowledged. MM CAR T-cell therapy is likely to be approved in Canada soon. Therefore, it is timely that we review the latest evidence for commercially available CAR T-cell therapy in multiple myeloma, with a focus on its relevance and impact in the Canadian setting. There will be challenges to access and strategies must be in place to ensure equitable care for all Canadians with MM. Alongside haematologists working in the immune effector cell therapy programs, providers in the community will also play a role in the ongoing monitoring and management of long-term side effects including opportunistic infections and late neurotoxicity. Full article

In the Industry 4.0 era of smart grids, the real-world problem of blackouts and cascading failures due to cyberattacks is a significant concern and highly challenging because the existing Intrusion Detection System (IDS) falls behind in handling missing rates, response times, and detection accuracy. Addressing this problem with an early attack detection mechanism with a reduced missing rate and decreased response time is critical. The development of an Intelligent IDS is vital to the mission-critical infrastructure of a smart grid to prevent physical sabotage and processing downtime. This paper aims to develop a robust Anomaly-based IDS using a statistical approach with a machine learning classifier to discriminate cyberattacks from natural faults and man-made events to avoid blackouts and cascading failures. The novel mechanism of a statistical approach with a machine learning (SAML) classifier based on Neighborhood Component Analysis, ExtraTrees, and AdaBoost for feature extraction, bagging, and boosting, respectively, is proposed with optimal hyperparameter tuning for the early discrimination of cyberattacks from natural faults and man-made events. The proposed model is tested using the publicly available Industrial Control Systems Cyber Attack Power System (Triple Class) dataset with a three-bus/two-line transmission system from Mississippi State University and Oak Ridge National Laboratory. Furthermore, the proposed model is evaluated for scalability and generalization using the publicly accessible IEEE 14-bus and 57-bus system datasets of False Data Injection (FDI) attacks. The test results achieved higher detection accuracy, lower missing rates, decreased false alarm rates, and reduced response time compared to the existing approaches. Full article

(1) Background: SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) is a promising therapeutic target to fight COVID-19, and many RdRp inhibitors nucleotide/nucleoside analogs, such as remdesivir, have been identified or are in clinical studies. However, the appearance of resistant mutations could reduce their efficacy. In the present work, we structurally evaluated the impact of RdRp mutations found at baseline in 39 patients treated with remdesivir and associated with a different degree of antiviral response in vivo. (2) Methods: A refined bioinformatics approach was applied to assign SARS-CoV-2 clade and lineage, and to define RdRp mutational profiles. In line with such a method, the same mutations were built and analyzed by combining docking and thermodynamics evaluations with both molecular dynamics and representative pharmacophore models. (3) Results: Clinical studies revealed that patients bearing the most prevalent triple mutant P323L+671S+M899I, which was present in 41% of patients, or the more complex mutational profile P323L+G671S+L838I+D738Y+K91E, which was found with a prevalence of 2.6%, showed a delayed reduced response to remdesivir, as confirmed by the increase in SARS-CoV-2 viral load and by a reduced theoretical binding affinity versus RdRp (ΔGbind_WT = −122.70 kcal/mol; ΔGbind_{P323L+671S+M899I} = −84.78 kcal/mol; ΔGbind_{P323L+G671S+L838I+D738Y+K91E} = −96.74 kcal/mol). Combined computational approaches helped to rationalize such clinical observations, offering a mechanistic understanding of the allosteric effects of mutants on the global motions of the viral RNA synthesis machine and in the changes of the interactions patterns of remdesivir during its binding. Full article

Several aromatic amines (AAs) are established by the International Agency for Research on Cancer as carcinogenic (group 1) or probable/possible carcinogens to humans (group 2A/2B). AAs can be found in mainstream and sidestream smoke from combustible tobacco products, as well as in certain environmental pollution and occupational exposure from several chemical industry sectors. Exposure to AAs can be estimated by measuring their concentrations in urine; however, information about the short-term and long-term stabilities of AAs in urine need to be characterized before conducting large-scale population studies on AA exposure and the potentially harmful effects of AA exposure. In this report, the storage stability of o-toluidine, 2,6-dimethylaniline, o-anisidine, 1-aminonaphthalene, 2-aminonaphthalene, and 4-aminobiphenyl fortified in pooled, filtered, non-smokers’ urine is analyzed by isotope dilution gas chromatography-triple quadrupole mass spectrometry (ID GC-MS/MS). The six AAs were measured in urine samples stored at ~20 °C (collection temperature), 4 °C and 10 °C (short-term transit temperatures), and −20 °C and −70 °C (long-term storage temperatures) over a 10-day period. All six analytes were stable for 10 days at transit and long-term storage temperatures but showed reduced recovery at 20 °C. The instability of the target AAs at 20 °C suggests that immediate storage of freshly voided urine at low temperatures is needed to attenuate degradation. A subset of the urine samples was analyzed following a longer storage duration at −70 °C: all AAs were stable for up to 14 months at this temperature. The stability of the six AAs in urine samples can be maintained at the various temperature levels and storage times expected in a typical study set. Full article

Information security in a controller area network (CAN) is becoming more important as the connections between a vehicle’s internal and external networks increase. Encryption and authentication techniques can be applied to CAN data frames to enhance security. To authenticate a data frame, a message authentication code (MAC) needs to be transmitted with the CAN data frame. Therefore, space for transmitting the MAC is required within the CAN frame. Recently, the Triple ID algorithm has been proposed to create additional space in the data field of the CAN frame. The Triple ID algorithm ensures every CAN frame is authenticated by at least 4 bytes of MAC without changing the original CAN protocol. However, since the Triple ID algorithm uses six header bits, there is a problem associated with low data compression efficiency. In this paper, we propose an algorithm that can remove up to 15 bits from frames compressed with the Triple ID algorithm. Through simulation using CAN signals of a Kia Sorento vehicle and an LS Mtron tractor, we show that the generation of frames containing compressed messages of 4 bytes or more is reduced by up to 99.57% compared to the Triple ID method. Full article