Search Results (3,423)

Influenza A virus (IAV) surveillance in swine relies heavily on molecular detection, yet RNA stability in diagnostic specimens such as oral fluids can be rapidly compromised when cold-chain conditions are not maintained. This pilot study evaluated the ability of four molecular-grade carbohydrates (20% trehalose, sorbitol, sucrose, and mannitol) and two commercial nucleic acid stabilizers (PrimeStore^® MTM and RNAlater^®) to preserve RT-qPCR-detectable IAV RNA in swine oral fluids exposed to field-relevant stress conditions. Oral fluid samples collected from pigs experimentally infected with H1N2 (Study 1: n = 150; DPIs 2, 3, 4) or with H1N2 and H3N2 (Study 2: n = 58; DPI 5) were subjected to storage at 25 °C for up to 144 h (Study 1) or 2, 5, 10, or 15 freeze–thaw cycles (Study 2), with DPIs (Study 1) or subtypes (Study 2) serving as biological replicates, given the limited sample size. IAV detection was quantified as efficiency standardized Cq values (ECq) and analyzed using a linear mixed-effects model. Overall, both carbohydrates (trehalose, sorbitol, sucrose) and commercial stabilizers maintained higher ECq values than untreated oral fluids under both thermal and freeze–thaw stress conditions. Due to the limited sample size, these findings should be interpreted cautiously, yet they demonstrate the potential utility of carbohydrates as a low-cost, non-inactivating alternative for stabilizing IAV RNA in field-collected oral fluids. Full article

Age-related macular degeneration (AMD) is the most common cause of blindness and vision impairment in individuals over 60 years of age in the United States (US). Despite this, current treatment options have limitations related to drug efficacy and durability. Gene therapy provides a potential solution by providing a more durable and longer- acting treatment option that can decrease treatment burden and improve long-term visual outcomes. This review presents the current treatment approaches, routes of administration, and vectors being investigated for gene therapy delivery in AMD. It also provides an update on the ongoing gene therapy clinical trials for dry and wet AMD. As these therapies advance into later-stage clinical trials, ophthalmologists need to be mindful of the many challenges pertaining to gene therapy delivery, including safety, limitations related to immunogenicity, long-term ocular and systemic side effects, and potential barriers to drug manufacturing and access. Continued efforts are required to improve precision, safety, and efficacy, including identifying the safest and most effective vectors and delivery routes, and minimizing potential adverse effects. In addition, guidelines need to be established to guide appropriate patient selection before gene therapy can be integrated into clinical practice. Full article

Background/Objectives: Electroanatomic mapping (EAM) provides high-resolution spatial and electrogram information, but the prognostic utility of quantitative EAM features has not been systematically evaluated with contemporary artificial intelligence (AI) methods. We investigated whether an AI analysis of quantitative EAM exports from the CARTO system enhances the prediction of major arrhythmic events (MAEs). Methods: In this retrospective, multicenter cohort study, 248 consecutive patients undergoing left ventricular EAM at four tertiary electrophysiology centers were analyzed. Numerical EAM descriptors (spatial coordinates, unipolar/bipolar voltages, local activation time, impedance) were transformed into derived metrics, including local activation heterogeneity (GR), late-potential extent (LAT), bipolar–unipolar discrepancy (VLT), and low-amplitude scar extent (Scar Areas), and were spatially normalized via spherical projection. Clinical, anamnestic, and imaging variables were integrated. Machine learning and deep learning models were trained with an 80:20 train/test split and evaluated using three-fold cross-validation. Performance metrics included area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and precision. Results: Models incorporating both clinical and AI-processed EAM features achieved high discriminatory performance (test AUC up to 0.92; accuracy up to 0.896). Specificity was consistently high (≈0.97–0.998), whereas sensitivity remained modest (≈0.39–0.58). Among the EAM-derived features, GR was the most consistently informative predictor across algorithms and analyses; VLT, LAT, and Scar Areas also contributed substantially. Regionally, basal sub-mitral, subaortic, and posterolateral basal-to-mid zones exhibited the strongest associations with MAEs. Conclusions: AI-driven quantitative analysis of left ventricular EAM exports augments risk stratification for MAEs beyond conventional clinical and binary EAM descriptors. Reflecting local conduction heterogeneity, GR emerged as the dominant EAM predictor. Prospective validation in larger, disease-specific cohorts and real-time integration within EAM platforms are warranted. Full article

Background: Hormone receptor-positive (HR+), Human Epidermal growth factor Receptor 2 (HER2-negative) metastatic breast cancer (MBC) represents a substantial proportion of breast cancer cases in Saudi Arabia. Despite the established efficacy of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, particularly Palbociclib, in randomized control trials, real-world data from local institutions in Saudi Arabia remain limited. Objectives: This study aimed to evaluate progression-free survival (PFS), overall survival (OS), and toxicity profile among HR+, HER2-negative MBC female patients treated with Palbociclib at King Fahad Medical City (KFMC). Methods: A retrospective study was conducted on female patients with HR+/HER2-negative MBC treated with oral palbociclib combined with endocrine therapy (ET) at KFMC between January 2021 and September 2024. Data were collected from electronic health records. Descriptive statistics were conducted using mean for continuous variables and frequency for categorical variables. Survival analyses were conducted using Cox regression, log-rank tests and Kaplan–Meier analysis. Results: A total of 169 female patients with HR+/HER2− MBC were included. In the first-line setting, the median PFS was 20.14 months (95% CI: 14.65–30.49), compared with 11.3 months (95% CI: 7.98–not estimable) in the second-line setting. For OS, the median OS values were 53.1 months (95% CI: 41.2–not estimable) in the first-line group and 23.7 months (95% CI: 18.5–not estimable) in the second-line group. Significant predictors of shorter PFS included age, Body Mass Index (BMI), type of ET, cancer type, line of therapy, family history of cancer, and history of VTE. Visceral metastasis (HR = 3.087; p = 0.0229) and ECOG performance status of 4 (HR = 13.86; p = 0.0156) were associated with significantly shorter OS. The most common hematological adverse events (AEs) were neutropenia (45.6%), followed by anemia (5.9%), leukopenia (5.3%), and back pain (5.3%). Most toxicities were managed with dose reduction, holding treatment, or supportive care. Conclusions: Palbociclib demonstrated favorable survival outcomes and a manageable safety profile, with neutropenia being the most common AE. This study provides region-specific real-world evidence supporting the use of Palbociclib in HR+/HER2− MBC. These findings align with global trial data and highlight the importance of individualized treatment in clinical practice. Full article

Despite the significant potential of ocean wave energy, the high cost of the generated power remains a major challenge. This highlights the need for innovative conceptual designs that enhance energy conversion while maintaining comparable implementation and installation costs. Recently, the concept of Variable-Shape Buoy Wave Energy Converters (VSB WECs) was introduced that uses flexible buoy material. While many studies have demonstrated the improved performance of VSB WECs compared to Fixed-Shape Buoy Wave Energy Converters (FSB WECs) through numerical simulations, analytical validation is essential to support these findings. This paper presents an analytical derivation of the theoretical limit of power absorption for VSB WECs using the complex-conjugate criteria for the heave motion. In this study, a multi-degree-of-freedom (multi-DoF) VSB WEC model is developed using a thin spherical shell representation, incorporating Rayleigh–Ritz and Love approximations under the assumptions of small deformations and axisymmetric vibration. Hydrodynamic coefficients are computed using a Boundary Element Method (BEM) software. The variation in the theoretical power absorption limit with Young’s modulus is analyzed across a range of elastic materials. As a validation step, the derived theoretical limit criterion is applied to the standard reduced-order single-DoF model of an FSBWEC, successfully yielding the exact theoretical limit reported in the literature. Full article

A recent publication proposed that the main biological function of chromosomal toxin–antitoxin systems (TASs) in free-living bacteria is to optimize fitness by mediating K Sensing and Control via a Nutrient-Responsive Cybernetic System. Viable cell density data were consistent with analog (continuous) regulation of population dynamics and cellular physiology throughout the life cycle; however, exactly how bacteria utilize TASs to regulate this was not explained in that publication. Two different concepts of injury have been proposed in the field of microbiology: (1) injury due to external physical and chemical stresses, which lead to sublethal (reversible) or lethal (irreversible) injury depending on the degree of injury, and (2) injury due to internal, self-inflicted stresses mediated by TA toxins. While self-inflicted injury due to TA toxins has been recognized as playing a role in growth arrest and dormancy, which can be reversed by repair, there is little support for TA toxins causing irreversible programmed cell death under normal physiological conditions. The purpose of the present paper was to explain how merging the above two concepts of injury might reveal how TASs optimize the fitness of free-living bacteria under normal physiological conditions by continuously regulating the ratio of injury: repair throughout the life cycle. Full article

A diverse range of 4-dimethylaminopyridinium (DMAP) bis(trifluoromethylsulfonyl)-amide ionic liquids with specific functionalities (alkyl, alkoxy, hydroxyalkyl and benzyl) were designed, characterized and compared with their pyridinium analogs in terms of their physical and radiolytic properties. The influence of the dimethylamino group on ionic liquid structure was investigated by X-ray diffraction and molecular dynamics simulations. The influence of the electron-donating ability of the dimethylamino-substituted cation is evident in the differences in the electronic density of states between the DMAP and pyridinium ILs. This leads to substantial changes in the radical transients observed in pulse radiolysis of the neat ILs. It was found that the DMAP salts were higher melting, more viscous and less conducting than their pyridinium analogs. However, the DMAP salts exhibited higher thermal stabilities and could therefore be useful for high-temperature applications. Full article

Iron oxide nanoparticles have emerged as multifunctional compounds with prominent potential in cancer theranostics, particularly in photothermal therapy (PTT) and photodynamic therapy (PDT). Their unique electronic and crystal structures, such as the dispersion of Fe²⁺ and Fe³⁺ ions and d-orbital splitting, contribute to their magnetic and catalytic properties. In PTT, Fe₃O₄ nanoparticles exhibit moderate near-infrared (NIR) absorption and photothermal conversion efficiency, which can be enhanced through adjustments in particle size, surface modification, and combinations with other components. In PDT, Fe₃O₄ nanoparticles demonstrate intrinsic peroxidase-like catalytic activity, facilitating Fenton and photo-Fenton reactions that generate reactive oxygen species (ROS), including hydroxyl radicals (^•OH), thereby amplifying oxidative stress in cancer cells. These nanoparticles can also function as carriers for photosensitisers (PS), promoting targeted delivery and enhanced ROS generation. Multifunctional nanomaterials that integrate Fe₃O₄ with other therapeutic agents and targeting ligands have demonstrated synergistic antitumour effects through amplified photothermal, photodynamic, chemodynamic, and chemotherapeutic mechanisms. Despite certain drawbacks, such as relatively low NIR absorption and challenges in optimising delivery and light activation, ongoing improvements in Fe₃O₄-based nanoplatforms present significant potential for enhancing treatment outcomes and the precision of cancer therapy. This article systematically explores the synergistic role of Fe₃O₄ nanoparticles in PTT and PDT, encompassing their magnetic and catalytic characteristics. Additionally, it focuses on multifunctional hybrid nanoplatforms that combine Fe₃O₄ with targeting or imaging agents, highlighting their potential to enhance therapeutic precision. Full article

Low back pain associated with exposure to whole-body vibration (WBV) is common among agricultural workers, and seated posture significantly affects health outcomes from WBV exposure. Current posture assessment methods rely on manual observation or body-worn sensors, which are labor-intensive and impractical for continuous monitoring. We developed a machine learning approach to classify seated posture using force sensors and accelerometers integrated into a vibration sensing seat pad for use in agricultural machinery, avoiding the need for body-worn sensors. Twenty-four participants were exposed to WBV in different upper body postures while seat pad force and acceleration data were recorded. We compared four machine learning architectures: Logistic Regression, Random Forest, Support Vector Machine, and Recurrent Neural Network with Gated Recurrent Unit (GRU). The GRU architecture substantially outperformed baseline models, achieving 89% accuracy (weighted F1 = 0.89) in classifying forward and backward leaning postures. To our knowledge, this study demonstrates the first application of machine learning to classify seated postures from seat pad force measurements during WBV exposure. Temporal modeling with an 18 s window proved essential for accurate classification, enabling non-invasive, continuous posture monitoring. Full article

Background: Human physiology-based biomarkers, such as transcortical long-latency reflexes (LLRs) and movement control performance, are measurements used to evaluate human performance. We developed a method to assess human performance variables using a custom-designed visuomotor control device with the capability to examine performance accuracy and neurophysiological responses to unexpected perturbations. We assessed the internal consistency and reproducibility of this device during a shoulder tracking task including the performance accuracy and the transcortical long-latency reflexes during unexpected perturbations. Methods: 86 healthy young adults (49 females, right-handed, mean age 25.8 ± 9.5 years) were assessed for internal consistency across varying resistance and velocity conditions. We next determined test–retest reliability among 31 participants (17 females, right-handed, mean age 24.13 ± 3.8 years). We then determined the predictability of the LLRs and performance error during perturbations using the receiver operating characteristic analysis (ROC). Results: Our results supported excellent internal consistency, fair-to-good test–retest reliability for task performance accuracy, and fair-to-good transcortical LLR responses to perturbations (McDonald’s omega > 0.9; intraclass correlation coefficients (ICCs, 0.63–0.82)). Tracking accuracy, changes in movement velocity, and infraspinatus LLRs were effective predictors of perturbation conditions (receiver operating characteristics: AUC 0.72–0.90). Conclusions: These findings support that performance-based biomarkers have moderate-to-good reliability and neurophysiology-based biomarkers have fair-to-good reliability when assessing human shoulder performance among healthy adults. Studies are currently underway to determine if these measures are reproducible across other joint movements and among people with musculoskeletal and central nervous system injury. Full article

Background: Ceftobiprole is an advanced-generation cephalosporin approved in Europe in 2013 for various indications, and in the United States (US) in 2024 for community-acquired bacterial pneumonia (CABP), acute bacterial skin and skin structure infections, and Staphylococcus aureus bacteremia, including right-sided endocarditis. Methods: The in vitro activity of ceftobiprole and comparators was evaluated against 2793 Streptococcus pneumoniae causing lower respiratory tract infections in 32 US sites (2016–2020), including against subsets from various geographic regions, resistance phenotypes and prevalent serotypes. Results: Ceftobiprole inhibited 99.5% of all S. pneumoniae at the MIC of ≤0.5 mg/L (MIC_50/90, 0.015/0.25 mg/L). Susceptibilities of 98.2% to 100% were observed for ceftobiprole against isolates originating from each surveyed year or each US Census Division. Ceftobiprole retained activity against isolates resistant to macrolides (98.8%), tetracycline (98.2%), oral penicillin (95.4%), against multidrug-resistant isolates (97.0%), and various serotypes (93.8–100%). Ceftriaxone (97.4%) and amoxicillin–clavulanate (95.1%) also showed elevated susceptibilities overall, but inconsistent results and lower than those observed for ceftobiprole were noted against isolates with elevated penicillin MIC or specific serotypes (i.e., 19A). Conclusions: These in vitro results, coupled with documented clinical efficacy, indicate that ceftobiprole is a valuable option to treat CABP caused by S. pneumoniae in the US. Full article

Printed electronics have emerged as a versatile manufacturing platform for next-generation biosensors, enabling on-demand and low-cost fabrication of functional devices on flexible, stretchable, and unconventional substrates. One major challenge in this field lies in the sintering of printed features, as conventional high-temperature processing is incompatible with polymeric substrates and thermally sensitive biological components. Low-temperature sintering inks, typically processed below 200 °C or even at room temperature, have become a critical enabling technology for bio-integrated electronics. This review provides an overview of the current state-of-the-art and key challenges associated with low-temperature sintering inks for printed bioelectronics. We discuss inks based on metal nanoparticles, metal–organic decomposition precursors, metal oxides, chalcogenides, and hybrid material systems. The emphasis is on how ink chemistry, ligand selection, and precursor structure govern rheology, stability, and sintering behavior. In addition, key low-temperature sintering and curing strategies, including thermal, photonic, laser, plasma, microwave, and chemical sintering, are compared in terms of energy delivery, densification mechanisms, and substrate compatibility. Finally, we outline emerging directions towards low temperature and room-temperature sintering inks, and sustainable biobased ink formulations, and discuss their applications for wearable, implantable, and soft biosensing platforms. Full article

Closed-loop vasopressor systems integrate real-time blood pressure monitoring with automated decision logic to support hemodynamic stability in perioperative and critical care environments. These technologies sit at the intersection of biomedical sensing, signal processing, and clinician-supervised automation: the quality, latency, and failure behavior of the monitoring input can directly shape controller performance, safety margins, and clinical usability. In this comprehensive review, we synthesize the major closed-loop vasopressor architectures reported in the literature, examine how sensor modality and signal integrity influence algorithm behavior, and summarize recurrent reliability vulnerabilities spanning sensors, control logic, and device integration. We organize the field through an end-to-end information pipeline—monitoring input, signal conditioning and quality assessment, decision and control strategy, actuation via infusion technology, and supervisory safety layers—highlighting common performance metrics used to benchmark control quality. We then discuss clinical validation patterns across settings, emphasizing practical considerations for deployment and the evidence gaps that remain most relevant to high-risk populations. Finally, we propose reporting and validation priorities for future studies, with a focus on sensor robustness, transparency of algorithm design, integration safeguards, and standardized documentation of failures and overrides. Full article

Objectives: The primary objective was to evaluate the antimicrobial susceptibility of Pseudomonas aeruginosa causing infection in elderly (≥65 years old) patients hospitalized in intensive care units (ICUs) of United States medical centers. Susceptibility results from isolates of elderly patients in ICUs were compared to isolates from elderly patients not in ICUs (elderly non-ICU) and adult ICU patients (18 to 64 years old; adult ICU). Methods: P. aeruginosa isolates were consecutively collected from 74 US medical centers in 2021–2025 and susceptibility tested by reference broth microdilution in the monitoring laboratory (Element Iowa City [JMI Laboratories]). The organism collection included 999 isolates from elderly ICU, 2027 isolates from elderly non-ICU, and 1022 isolates from adult ICU patients. Results: The most active agents against P. aeruginosa from all three patient groups were ceftazidime-avibactam (95.8% to 97.3% susceptible), ceftolozane-tazobactam (96.0% to 98.3% susceptible), imipenem-relebactam (97.6% to 98.7% susceptible), and tobramycin (91.4% to 94.7% susceptible). Susceptibility to piperacillin-tazobactam, ceftazidime, cefepime, meropenem, and imipenem were markedly lower among isolates from elderly and adult ICU patients compared to elderly non-ICU patients. Susceptibility to levofloxacin and tobramycin were lower among isolates from adult ICU patients compared to elderly ICU and non-ICU patients. Moreover, the frequency of multidrug-resistant (MDR) isolates was markedly higher among elderly (18.4%) and adult (22.4%) ICU patients compared to elderly non-ICU (11.0%) patients. An annual analysis of susceptibility to selected β-lactams showed a slight variation in susceptibility rates without a clear trend. Conclusions: Ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-relebactam were highly active and exhibited similar coverage against a large contemporary collection of P. aeruginosa isolates from ICU elderly, non-ICU elderly, and ICU adult patients. Cross-resistance among these β-lactamase inhibitor combinations (BLICs) varied markedly, indicating that all three should be tested in the clinical laboratory and available for clinical use. Full article