Search Results (1,312)

Background/Objectives: Anti-drug antibody (ADA) formation can impact the safety, pharmacokinetics, and/or efficacy of biotherapeutics, including monoclonal antibodies (mAbs). Current strategies for ADA/immunogenicity risk prediction of mAbs include in silico algorithms, T cell proliferation assays, MHC-associated peptide proteomics assays (MAPPs), and dendritic cell internalization assays. However, B cell-mediated responses are not assessed in these assays. B cells are professional antigen-presenting cells (APCs) and secrete antibodies toward immunogenic mAbs. Therefore, methods to determine B cell responses would be beneficial for immunogenicity risk prediction and may provide a more comprehensive assessment of risk. Methods: We used a PBMC culture method with the addition of IL-4, IL-21, B cell activating factor (BAFF), and an anti-CD40 agonist mAb to support B cell survival and activation. Results: B cells in this assay format become activated, proliferate, and secrete IgG. A panel of 51 antibodies with varying clinical immunogenicity rates were screened in this assay with IgG secretion used as a readout for immunogenicity risk. IgG secretion differed among test articles but did not correlate with the clinical immunogenicity rating. Conclusions: This dataset highlights the challenges of developing a B cell assay for immunogenicity risk prediction and provides a framework for further refinement of a B cell-based assay for immunogenicity risk prediction of mAbs. Full article

Background: Myocarditis is associated with increased mortality due to complications such as cardiogenic shock and arrhythmia. Trends of myocarditis-related mortality in the United States, along with demographic and regional disparities and changes during the COVID-19 pandemic, are unknown. Methods: We used the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database to extract data for myocarditis deaths from 1999 to 2023. The Joinpoint Regression Program was used to analyze long-term trends in mortality, and R Studio (version 4.4.1) was used to calculate expected and excess mortality for 2020 to 2023. Results: There were 33,016 myocarditis-related deaths from 1999 to 2023. The age-adjusted mortality rate (AAMR) of myocarditis deaths decreased by 46.08% from 7.40 (95% CI: 7.04–7.76) in 1999 to 3.99 (95% CI: 3.74–4.23) in 2019, with an APC of −2.59 (95% CI: −2.97 to −2.24). From 2019 to 2021, the AAMR increased by 46.62% to 5.85 (95% CI: 5.56–6.14) by 2021 (2019–2021 APC 22.3%*), reversing the gains of the previous two decades. By 2023, the AAMR recovered to 4.33 (95% CI: 4.09 to 4.58), though mortality was still higher than expected from pre-pandemic trends. From 2020 to 2023, there were 40.12% more deaths than expected, with 54.94% higher mortality in 2021. Briefly, 70.33% of excess myocarditis-related deaths also had COVID-19, with a peak of 76.15% of excess myocarditis deaths in 2021 being reported as involving COVID-19 infection. Significant disparities in mortality trends persisted, with males, NH Black or African Americans, and the elderly having higher mortality rates. Conclusions: Myocarditis mortality decreased in the United States from 1999 to 2019 but significantly increased during the COVID-19 pandemic years 2020 and 2021. At the height of the pandemic, COVID-19 infection contributed to almost three-quarters of excess myocarditis mortality. Significant disparities in myocarditis mortality persisted from 1999 to 2023. Full article

Background: Fungal infections, particularly those caused by Candida species, pose a serious threat to immunocompromised individuals, and therapeutic options are limited due to toxicity and resistance concerns. This in vitro study aimed to explore the feasibility of using liquid fractions of autologous platelet concentrates (APCs), namely concentrated platelet-rich fibrin (c-PRF) and liquid-phase concentrated growth factor (LPCGF), as carriers for antifungal drugs. Methods: The research was conducted in two phases: first, to evaluate the inherent antifungal properties of different APCs; and second, to assess their effectiveness as drug carriers for fluconazole and voriconazole against Candida albicans, Candida glabrata, and Candida krusei. Results: Results showed that APCs alone exhibited no direct antifungal effects. However, when combined with antifungal agents, notable inhibition zones were observed—especially with voriconazole against C. krusei and fluconazole against C. glabrata using c-PRF. Both c-PRF and LPCGF were compatible with the drugs and did not hinder clot formation. Conclusions: These findings suggest that APCs can act as effective vehicles for localized antifungal drug delivery and warrant further investigation for clinical application in treating fungal-related oral diseases. Full article

Gastrointestinal (GI) parasitic infections in non-human primates are of growing concern due to their implications for both veterinary and public health. Long-tailed macaques (Macaca fascicularis), commonly found in peri-urban and temple environments in Southeast Asia, may act as reservoirs for zoonotic parasites, posing risks to humans and domestic animals. This study investigated the prevalence and species diversity of GI parasites in free-ranging macaques from four provinces in Northeast Thailand (Loei, Khon Kaen, Bueng Kan, and Sisaket). A cross-sectional study was conducted between April and May 2025. A total of 445 fecal samples were examined using two parasitological techniques: agar plate culture (APC) and the formalin–ethyl acetate concentration technique (FECT). The overall prevalence of parasitic infection was 86.5%, with Strongyloides sp. (65.2%) as the most prevalent helminth and Balantioides coli-like (29.5%) and Entamoeba histolytica-like (28.8%) as the predominant protozoa. Other parasites identified included helminths (Trichuris sp., Ascaris sp.) and protozoa (Blastocystis sp., Iodamoeba bütschlii, Entamoeba coli, and Chilomastix mesnili). Mixed infections were frequently observed, with both helminths and protozoa co-occurring in 37.3% of cases. The high infection rates and parasite diversity reflect substantial environmental contamination and sustained transmission cycles. These findings underscore the importance of integrated surveillance in wildlife populations and the need for One Health-based approaches to minimize zoonotic transmission risks at the human–animal–environment interface. Full article

As China’s primary grain-producing area, the Luxi Plain is rich in groundwater resources, which serves as the main water supply source in this region. Investigating the evolution of hydrochemical characteristics and influencing factors of groundwater in this region is crucial for maintaining the safety of groundwater quality and ensuring the high-quality development of the water supply. This study took Liaocheng City in the hinterland of the Luxi Plain as the study area. To clarify the hydrochemical characteristics evolution trend of groundwater in the area, the hydrochemical characteristics of shallow groundwater in recent years were systematically analyzed. The methods of ion ratio, correlation analysis, Gibbs and Gaillardet endmember diagrams, as well as the application of the absolute principal component scores–multiple linear regression (APCS-MLR) receptor model were used to determine the contribution rates of different ion sources to groundwater and to elucidate the driving factors behind the evolution of groundwater chemistry. Results showed significant spatiotemporal variations in the concentrations of major ions such as Na⁺, SO₄²⁻, and Cl⁻ in groundwater in the study area, and these variations demonstrated an overall increasing trend. Notably, the increases in total hardness (THRD), SO₄⁻, and Cl⁻ concentrations were particularly pronounced, while the variations in Na⁺, Mg²⁺, Ca²⁺ and other ions were relatively gradual. APCS-MLR receptor model analysis revealed that the ions such as Na⁺, Ca²⁺, Mg²⁺, SO₄²⁻, Cl⁻, HCO₃⁻ and NO₃⁻ all have a significant influence on the hydrochemical composition of groundwater due to the high absolute principal component scores of them. The hydrochemical characteristics of groundwater in the study area were controlled by multiple processes, including evaporites, silicates and carbonates weathering, evaporation-concentration, cation alternating adsorption and human activities. Among the natural driving factors, rock weathering had a greater influence on the evolution of groundwater hydrochemical characteristics. Moreover, mining activities were the most important anthropogenic factor, followed by agricultural activities and living activities. Full article

Background: Kidney disease is a significant cause of morbidity and mortality in the United States. However, less is known about its burden specifically among older adults. Methods: We analyzed deaths among U.S. adults aged 65 and older between 2018 and 2023 where kidney disease was listed as the primary cause of death, using data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER). We examined overall and subgroup-specific death counts stratified by sex, race, ethnicity, and geographic location. Trends from 1999 to 2023 were also assessed. Results: Between 2018 and 2023, there were 263,436 deaths among adults aged 65+ with kidney disease as the primary cause, accounting for 81.5% of all kidney disease deaths during this period. Mortality rates were significantly higher among males compared to females (age-adjusted mortality rate (AAMR) ratio = 1.42, 95% CI: 1.42–1.43) and among Black Americans compared to White Americans (AAMR ratio = 1.94, 95% CI: 1.93–1.95). From 1999 to 2009, kidney disease mortality rates increased (annual percent change (APC) = 1.40, 95% CI: 0.90, 2.09), declined between 2009 and 2012 (APC = −5.35, 95% CI: −6.59, −2.33), and remained stable from 2012 to 2023. Conclusions: This majority of kidney disease deaths in the U.S. occur among older adults. While mortality briefly declined between 2009 and 2012, progress has since stalled. Persistent disparities by race and geography highlight the need for targeted research and interventions to reduce kidney disease mortality among older adults. Full article

Asynchronous-pouring construction (APC) technology employs a suspended hanging basket directly supported by corrugated steel webs (CSWs) with high shear strength, significantly enhancing construction efficiency. To further elucidate the characteristics of APC and promote its application in prestressed concrete (PC) composite box girder bridges with CSWs, this study analyzes the sustainable development of APC from two aspects, including environmental impact and economic performance. Finite element models of APC and traditional balanced cantilever construction (TBCC) were established for the case bridge with a main span of 105 m. The stress distribution and deflection of the main girder in the cantilever construction state are compared with field measurements, and the variations in stress and deflection in typical sections during construction are analyzed. Additionally, a simplified theoretical method is proposed for calculating stress and deflection in PC composite girder bridges during the cantilever construction stage using APC. Results demonstrate that APC demonstrates significant advantages in reducing economic costs and minimizing long-term environmental impacts. Furthermore, this method ensures acceptable stress and deflection throughout construction. The proposed simplified formula for CSW deflection in the maximum segment agrees well with both measured data and finite element results, providing a valuable reference for deflection calculation in APC applications. Full article

Oral cancer, the most common form of head and neck cancer, is worldwide a serious public health problem. Most patients present a locally advanced disease, and face poor prognosis, even with multimodality treatment. They may also develop second primary tumors in the entirety of their upper aerodigestive tract. The most altered signaling pathways are the PI3K/AKT/mTOR, TP53, RB, and the WNT/β-catenin pathways. Genomic and molecular cytogenetic analyses have revealed frequent losses at 3p, 8p, 9p, and 18q, along with gains at 3q, 7p, 8q, and 11q, and several genes frequently affected have been identified, such as TP53, CCND1, CTTN, CDKN2A, EGFR, HRAS, PI3K, ADAM9, MGAM, SIRPB1, and FAT1, among others. Various epigenetic alterations were also found, such as the global hypomethylation and hypermethylation of CDKN2A, APC, MGMT, PTEN, CDH1, TFP12, SOX17, GATA4, ECAD, MGMT, and DAPK. Several microRNAs are upregulated in oral cancer, including miR-21, miR-24, miR-31, miR-184, miR-211, miR-221, and miR-222, while others are downregulated, such as miR-203, miR-100, miR-200, miR-133a, miR-133b, miR-138, and miR-375. The knowledge of this molecular pathogenesis has not yet been translated into clinical practice, apart from the use of cetuximab, an EGFR antibody. Oral tumors are also genetically heterogenous and affect several pathways, which means that, due to the continuous evolution of these genetic alterations, a single biopsy is not sufficient to fully evaluate the most adequate molecular targets when more drugs become available. Liquid biopsies, either resorting to circulating tumor cells, extracellular vesicles or cell-free nucleic acids, have the potential to bypass this problem, and have potential prognostic and staging value. We critically review the current knowledge on the molecular, genetic and epigenetic alterations in oral cancer, as well as the applications and challenges of liquid biopsies in its diagnosis, follow-up, and prognostic stratification. Full article

Vehicular visible light communication (VVLC) with ultralow electromagnetic interference has great potential to propel the growth of the Internet of Vehicles (IoV). However, ensuring quick response times and minimal delays in VVLC is a significant challenge brought on by fast-moving vehicles. In response to this problem, we propose a heuristic optical flow scheduling algorithm. First, the optical flow scheduling problem of VVLC is built as a multi-objective optimization model considering the makespan, delay, schedulable ratio, and bandwidth utilization with non-conflict constraints. Second, an improved artificial plant community (APC) algorithm with enhanced global and local search capabilities is proposed to achieve low-delay communication for time-sensitive optical flows. Finally, a series of benchmark experiments are conducted to show that the proposed algorithm can efficiently schedule optical flows with minimal delay. The cost of this algorithm is very low, and it is suitable for deployment on edge computing platforms such as vehicles. Full article

Background: Cardiac arrest remains a significant public health challenge with variable mortality trends across different demographics and regions, affecting healthcare planning and intervention strategies. We conducted this study to analyze cardiac arrest-related mortality trends from 1999 to 2023 and predict future trends up to 2035. Methods: This study analyzed data from 1999 to 2023, focusing on cardiac arrest as the primary cause of death (ICD-10: I46). Age-adjusted mortality rates (AAMRs) were standardized according to the 2000 U.S. Census. Joinpoint regression was utilized to calculate annual percentage change (APC), and an ARIMA model with Python 3.10 was used for mortality predictions. Results: A total of 365,608 cardiac arrest-related deaths were recorded in the USA from 1999 to 2023. There was a sharp decline in mortality rate until 2001 (APC: −10.35, p < 0.05), followed by a slowed decline until 2013 (APC: −2.91, p < 0.05), and then a gradual uptrend. Males exhibited a higher AAMR (5.8, 95% CI: 5.8–5.9) compared to females (4.2, 95% CI: 4.1–4.2). African Americans had the highest AAMR (8.9, 95% CI: 8.9–9), followed by Caucasians (4.8, 95% CI: 4.8–4.9) and American Indians (3.5, 95% CI: 3.3–3.7). The South region of the US had the highest AAMR, followed by the Northeast, Midwest, and West. Alabama exhibited the highest AAMR, followed by Nevada and Hawaii. Predictive analysis suggests a potential stable slow downtrend in mortality rates by 2035 (AAMR: 4.28, 95% CI: −1.8–10.4). Conclusions: The observed trends and future predictions underscore the importance of targeted public health interventions and healthcare planning to address cardiac arrest mortality. Full article

Mississippi has long been one of the most obese states in the U.S., with its obesity rates consistently exceeding the national average. The state’s severe obesity rate is also among the highest in the nation. This study utilized the 2011 to 2021 data from the Mississippi Behavioral Risk Factor Surveillance System (BRFSS) to conduct a comprehensive analysis of obesity and severe obesity trends in Mississippi by sex, age, and race and ethnicity. The data set included a BMI variable calculated by using self-reported height and weight, which the authors categorized into two obesity classification groups—obesity (BMI: 30.00 to 39.99) and severe obesity (BMI: 40.00 or greater)—and demographic characteristics such as sex, age, race and ethnicity. The data were analyzed using SAS 9.4 software to account for the complex design. Weighted prevalence estimates and associated standard errors (SEs) for obesity and severe obesity were calculated. Changes in the prevalence over time were assessed using logistic regression models. The prevalence estimates and SEs were exported to Joinpoint software to calculate the annual percentage change (APC) and associated 95% confidence intervals (CIs) and p-values for the trends. Our analysis of the data revealed a consistent increase in severe obesity, regardless of age, sex, or race. A concerning trend exists where individuals are moving from the obese category to the severely obese category, indicating a worsening trend in overall weight status. This is likely to accelerate the development of chronic disease and, hence, place additional strain on an economically disadvantaged state. Future research should explore the underlying drivers of this shift, including biological, behavioral, and socioeconomic factors, while also evaluating the effectiveness of existing obesity prevention and treatment programs. Full article

Membrane transporters are vital for solute movement and localisation across cellular compartments, particularly in extremophilic organisms such as Galdieriales. These red algae thrive in geothermal and metal-rich environments, where adaptive transporter systems contribute to their metabolic flexibility. While inventories of transporter genes in the species Galdieria sulphuraria have previously been compiled, their phylogenetic origins remain incompletely resolved. Here, we conduct a comparative phylogenetic analysis of three transporter families—Major Facilitator Superfamily (MFS). Amino acid–Polyamine–Organocation (APC) and the natural resistance–associated macrophage protein (Nramp)—selected from overexpressed transcripts in G. sulphuraria strain SAG 107.79. Using sequences from six Galdieriales species and orthologs from diverse taxa, we reconstructed maximum likelihood trees to assess conservation and potential horizontal gene transfer (HGT). The MFS subfamilies revealed contrasting patterns: sugar porters (SPs) exhibited polyphyly and fungal affinity, suggesting multiple HGT events, while phosphate:H⁺ symporters (PHSs) formed a coherent monophyletic group. APC sequences were exclusive in G. sulphuraria and extremophilic prokaryotes, indicating a likely prokaryotic origin. In contrast, Nramp transporters were broadly conserved across eukaryotes and prokaryotes, showing no signs of recent HGT. Together, these findings highlight the mosaic evolutionary history of membrane transporters in Galdieriales, shaped by a combination of vertical inheritance and taxon-specific gene acquisition events, and provide new insight into the genomic strategies underpinning environmental resilience in red algae. Full article

Current systemic therapies for advanced colorectal cancer (CRC) have limited efficacy, so more effective strategies for the treatment and prevention of CRC are needed. The majority of colorectal cancers are initiated by mutations in Wnt signalling pathway genes, including mutations in the APC gene, which result in a truncated APC protein and lead to excess signalling from β-catenin and the formation of pre-cancerous adenomas. The aim of this study was to determine if targeting the Wnt pathway in combination with pro-apoptotic mimetics altered the proliferative capacity or viability of human colorectal adenoma cells. Patient-derived colorectal adenoma organoid cultures were established from colon adenoma tissue collected by colonoscopy and recapitulated the histopathology of primary colorectal adenoma tissue. The growth of colorectal adenoma organoids is inhibited by the Wnt-signalling antagonist pyrvinium pamoate (PP) and a pro-apoptotic inhibitor of BCL-XL but not BCL-2 (venetoclax) or MCL-1 inhibitors. At low concentrations, the PP and the BCL-XL inhibitor combination demonstrated potent synergy and induced apoptosis in APC-defective patient-derived adenoma organoids, even in the presence of oncogenic KRAS or BRAF mutations, providing a new strategy for colon cancer prevention. Full article

Exposure to high-linear energy transfer (LET) heavy ions, such as ²⁸Si, poses a significant cancer risk for astronauts. While previous studies have linked high-LET radiation exposure to persistent oxidative stress and dysregulated stress responses in intestinal crypt cells with an increased risk of tumorigenesis, the relationship between IR-induced oxidative DNA damage and intestinal cancer risk remains incompletely understood. Here, we investigated the time-dependent effects of ²⁸Si-ion radiation on intestinal tumorigenesis and oxidative DNA damage in Apc^1638N/+ mice, a model for human intestinal cancer predisposition. Male Apc^1638N/+ mice were exposed to 10 cGy of either γ-rays (low-LET) or ²⁸Si-ions (high-LET), and intestinal tumor burden was assessed at 60 and 150 days post-irradiation. While both radiation groups showed modest, non-significant tumor increases at 60 days, ²⁸Si-irradiated mice exhibited an approximately 2.5-fold increase in tumor incidence by 150 days, with a higher incidence of invasive carcinomas compared to γ and sham groups. Serum 8-OxodG levels, a marker of systemic oxidative stress, were significantly elevated in the ²⁸Si-ion group, correlating with increased intestinal 8-OxodG staining. Additionally, assessment of the proliferation marker Cyclin D1 and metaplasia marker Guanylyl Cyclase C (GUCY2C) also revealed significant crypt cell hyperproliferation accompanied by increased metaplasia in ²⁸Si-exposed mouse intestines. Positive correlations between serum 8-OxodG and tumor-associated endpoints provide compelling evidence that exposure to ²⁸Si-ions induces progressive intestinal tumorigenesis through sustained oxidative DNA damage, crypt cell hyperproliferation, and metaplastic transformation. This study provides evidence in support of the radiation quality-dependent progressive increase in systemic and intestinal levels of 8-OxodG during intestinal carcinogenesis. Moreover, the progressive increase in oxidative DNA damage and simultaneous increase in oncogenic events after ²⁸Si exposure also suggest that non-targeted effects might be a significant player in space radiation-induced intestinal cancer development. The correlation between serum 8-OxodG and oncogenic endpoints supports its potential utility as a predictive biomarker of high-LET IR-induced intestinal carcinogenesis, with implications for astronaut health risk monitoring during long-duration space missions. Full article

In this paper, water quality samples were collected from 215 sampling sites in Huaibin County, Xinyang District, Huaihe River Basin, in May 2024, and 11 key indicators of groundwater quality were analyzed. On the basis of hydrochemical statistics and water quality analysis to determine the water quality categories and characteristic pollutants, principal component analysis (PCA) was used to summarize the main driving factors affecting water quality, and it was combined with the absolute principal component score-multiple linear regression receptor model (APCS-MLR model) to further quantify the degree of influence of anthropogenic and natural factors on groundwater quality in the basin. The results showed that about 52% of the groundwater exceeded the Class III water standard of Groundwater Quality Standard (GB/T 14848-2017). Four types of principal component factor affecting the water quality were extracted by principal component analysis (PCA), which were dissolved filtration, migration enrichment (37.39%), agricultural surface pollution (15.52%), leaching and agricultural surface pollution (11.07%) and industrial pollution factor (10.24%). The APCS-MLR model was used to further quantify the effects of various anthropogenic and natural factors on water quality. The average contributions of the five factors to the groundwater quality in the basin were 66.51%, 51.66%, 19.61% and 78.13%, respectively, and the average fitting coefficient of the measured and predicted values of each index was 0.74. This method is highly relevant to the calculation of the allocation of the groundwater pollution sources, and it is suitable for the analysis of the groundwater pollution sources. Full article