Search Results (162)

Background: Lung cancer remains the leading cause of cancer-related mortality worldwide. Advances in screening, diagnosis, and management have transformed clinical practice, particularly with the integration of immunotherapy and target therapies. Methods: A systematic literature search was carried out for the period between October 2016 to September 2024. Phase II and III randomized trials evaluating ICI monotherapy, ICI–chemotherapy combinations, and dual ICI regimens in patients with advanced NSCLC were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (AEs). Results: PD-1-targeted therapies demonstrated superior OS compared to PD-L1-based regimens, with cemiplimab monotherapyranking highest for OS benefit (posterior probability: 90%), followed by sintilimab plus platinum-based chemotherapy (PBC) and pemetrexed—PBC. PFS atezolizumab plus bevacizumab and PBC, and camrelizumab plus PBC were the most effective regimens. ICI–chemotherapy combinations achieved higher ORRs but were associated with greater toxicity. The most favorable safety profiles were observed with cemiplimab, nivolumab, and avelumab monotherapy, while atezolizumab plus PBC and sugemalimab plus PBC carried the highest toxicity burdens. Conclusions: In PD-L1-unselected advanced NSCLC, PD-1 blockade—particularly cemiplimab monotherapy—and rationally designed ICI–chemotherapy combinations represent the most efficacious treatment strategies. Balancing efficacy with safety remains critical, especially in the absence of predictive biomarkers. These findings support a patient-tailored approach to immunotherapy and highlight the need for further biomarker-driven and real-world investigations to optimize treatment selection. Full article

Acute myeloid leukemia (AML), a heterogeneous and aggressive clonal disease, is predominantly observed in older individuals, with a median age at diagnosis of 68–69 years. With the aging population, there is a significant increase in the occurrence of some genetic alterations, including detrimental gene mutations and cytogenetic abnormalities, and a higher incidence of secondary AML (s-AML) and therapy-related AML (t-AML), compared to younger AML patients. Outcomes of AML patients and their response to therapy are associated with the molecular features of AML subtypes and with individual variables. The current criteria for risk classification predict outcomes in younger AML patients treated with intensive chemotherapy but are less predictive for older AML patients treated with lower-intensity treatments. Thus, this review analyzes and discusses the development of new risk stratification models adapted to the study of older AML patients and how these new criteria may significantly contribute to a more rational classification and treatment of older AML patients. Full article

Background/Objectives: The clinically validated multiplex Oncuria bladder cancer (BC) assay quickly and noninvasively identifies disease risk and tracks treatment success by simultaneously profiling 10 protein biomarkers in voided urine samples. Oncuria uses paramagnetic bead-based fluorescence multiplex technology (xMAP^®; Luminex, Austin, TX, USA) to simultaneously measure 10 protein analytes in urine [angiogenin, apolipoprotein E, carbonic anhydrase IX (CA9), interleukin-8, matrix metalloproteinase-9 and -10, alpha-1 anti-trypsin, plasminogen activator inhibitor-1, syndecan-1, and vascular endothelial growth factor]. Methods: In a pilot study (N = 36 subjects; 18 with BC), Oncuria performed essentially identically across three different common analyzers (the laser/flow-based FlexMap 3D and 200 systems, and the LED/image-based MagPix system; Luminex). The current study compared Oncuria performance across instrumentation platforms using a larger study population (N = 181 subjects; 51 with BC). Results: All three analyzers assessed all 10 analytes in identical samples with excellent concordance. The percent coefficient of variation (%CV) in protein concentrations across systems was ≤2.3% for 9/10 analytes, with only CA9 having %CVs > 2.3%. In pairwise correlation plot comparisons between instruments for all 10 biomarkers, R² values were 0.999 for 15/30 comparisons and R² ≥ 0.995 for 27/30 comparisons; CA9 showed the greatest variability (R² = 0.948–0.970). Standard curve slopes were statistically indistinguishable for all 10 biomarkers across analyzers. Conclusions: The Oncuria BC assay generates comprehensive urinary protein signatures useful for assisting BC diagnosis, predicting treatment response, and tracking disease progression and recurrence. The equivalent performance of the multiplex BC assay using three popular analyzers rationalizes test adoption by CLIA (Clinical Laboratory Improvement Amendments) clinical and research laboratories. Full article

Antibiotic therapy is essential for managing bacterial infections, but rare yet serious hematological complications such as leukopenia and agranulocytosis may occur. These conditions, although uncommon, require timely diagnosis and intervention, particularly in vulnerable populations such as postpartum patients. This case report describes a 31-year-old puerperal woman who developed agranulocytosis after extended antibiotic treatment for a presumed multidrug-resistant infection. Initially treated with ceftriaxone and metronidazole, her therapy was later escalated to include ciprofloxacin, amoxicillin–clavulanic acid, and vancomycin. Enterococcus spp. and Staphylococcus aureus were isolated from multiple sites, although no systemic infection was confirmed. Bone marrow findings were consistent with agranulocytosis in the recovery phase. Despite improvements in infection markers, her leukocyte count progressively declined, reaching a nadir of 1.61 × 10⁹/L on the 19th day of therapy. Granulocyte-colony stimulating factor (G-CSF) therapy was initiated, resulting in hematological recovery. The patient was discharged with normal inflammatory markers and leukocyte counts. This case highlights the importance of diagnostic precision, rational antibiotic use, and timely hematologic assessment during prolonged antimicrobial treatment. Full article

Cell membranes are vital for living organisms and serve as a dynamic barrier between the internal and external environments. They are composed of a complex lipid bilayer embedded with proteins, allowing them to perform multiple functions like maintaining the cell structure, regulating which substances enter or leave the cell, and intercellular communication. Cellular functions are inherently linked to their membrane properties, and the heterogeneous nature of cell membranes makes the study of their physico-chemical properties extremely challenging. This review is intended to provide a comprehensive overview of the composition and physical features of the cell membrane, by focusing on the lipid and protein composition, and on the physical properties (like membrane stiffness or fluidity), highlighting how these characteristics influence cell functions. An insight into the similarities and differences from the membranes of extracellular vesicles (naturally secreted by almost all cell types) is also provided. The understanding of the physico-chemical properties of cell membranes might find application in different therapeutic fields, like disease diagnosis and development of novel drug delivery systems. Therefore, an overview of the literature works describing the rational design of biomimetic drug delivery systems is presented, focusing on the choice of lipid components, frequently inspired by the study of the composition of naturally secreted exosomes, and on the physical characterization of the systems. In the future, in-depth study of biologic vesicles might lead to the development of promising formulation for drug delivery, possibly enhancing the therapeutic outcomes of many pathologies, like cancer. Full article

Background: Antimicrobial resistance (AMR) is a public health concern worldwide, particularly in low-to-middle-income countries with few antimicrobial stewardship programs and few laboratories equipped for diagnosis. Methods: As point-prevalence surveys (PPSs) are a well-known tool for assessing antimicrobial use, we adjusted standardized Global-PPS for use in two hospitals in Benin and included an analysis based on the 2021 WHO AWaRe classification. Results: Of the 450 patients enrolled, 148 received antimicrobials (AMs) (overall prevalence 32.9%), most of them orally (54.2%). Both hospitals had a high rate of Access and Watch antibiotics use, and both prescribed mainly metronidazole. In four prescriptions, hospital A used a non-recommended association of antibiotics, such as ceftriaxone + sulbactam and ofloxacin + ornidazole. While hospital A prescribed predominantly amoxicillin + clavulanic acid (19/92; 21%) and ceftriaxone (14/92; 15%), hospital B prescribed ampicillin (24/120; 20%) and cefuroxime (14/120; n = 12%). In hospital B, surgical antimicrobial prophylaxis (SAP) was suboptimal. While there were no single-dose prophylaxis prescriptions, all one-day prophylaxis (SP2) involved ampicillin for cesarean sections. In patients in intensive care units, prolonged prophylaxis (>1 day, SP3) accounted for all postoperative prescriptions. Conclusions: These findings highlight the critical need for implementing antimicrobial stewardship programs, expanding diagnostic laboratory capacity to minimize empirical prescribing, and strengthening medical student training to ensure quality and rational antibiotic use, thereby addressing the growing challenge of resistance in resource-limited settings. Full article

Backgroud: Ovarian cancer is the deadliest gynecologic malignancy, with most patients presenting with peritoneal dissemination at diagnosis. Complete cytoreduction and sensitivity to platinum-based systemic chemotherapy remain the most significant prognostic factors. However, even after optimal first-line management, over half of patients relapse due to residual microscopic disease. Intraperitoneal chemotherapy aims to target this component, with normothermic intraperitoneal chemotherapy long-term (NIPEC-LT) and hyperthermic intraperitoneal chemotherapy (HIPEC) being the most studied approaches. While NIPEC-LT has demonstrated improved survival in select trials, concerns regarding toxicity and catheter-related complications have limited its adoption as standard care. Conversely, HIPEC has shown survival benefits, particularly in patients undergoing interval cytoreductive surgery (iCRS) after neoadjuvant chemotherapy, leading to its inclusion in clinical guidelines. However, HIPEC is administered as a single intraoperative treatment, limiting its prolonged effect. Objectives and Method: This study investigates the combination of HIPEC and postoperative NIPEC-LT in the BICOV-1 trial, a prospective, non-randomized phase I study evaluating the feasibility, safety, and oncologic outcomes. The primary objective is to assess the treatment completion rates and morbidity. The secondary endpoints include disease-free survival (DFS), overall survival (OS), and quality-of-life measures. Combining HIPEC and NIPEC-LT is a rational approach, as both have shown independent benefits and do not overlap in toxicity. HIPEC-induced biological changes may enhance the effectiveness of subsequent intraperitoneal chemotherapy. This trial will provide essential data for future phase II/III studies assessing the role of intensified intraperitoneal treatment in ovarian cancer management. Full article

SPR biosensors operate on the principle of evanescent wave propagation at metal–dielectric interfaces in total internal reflection conditions, with consequent photonic energy attenuation. This plasmonic excitation occurs in specific conditions of incident light wavelength, angle, and the dielectric refractive index. This principle has been the basis for SPR-based biosensor setups wherein mass/concentration-induced changes in the refractive indices of dielectric media reflect as plasmonic resonance condition changes quantitatively reported as arbitrary response units. SPR biosensors operating on this conceptual framework have been designed to study biomolecular interactions with real-time readout and in label-free setups, providing key kinetic characterization that has been valuable in various applications. SPR biosensors often feature antibodies as target affinity probes. Notably, the operational challenges encountered with antibodies have led to the development of aptamers—oligonucleotide biomolecules rationally designed to adopt tertiary structures, enabling high affinity and specific binding to a wide range of targets. Aptamers have been extensively adopted in SPR biosensor setups with promising clinical and industrial prospects. In this paper, we explore the growing literature on SPR setups featuring aptamers, specifically providing expert commentary on the current state and future implications of these SPR aptasensors for drug discovery as well as disease diagnosis and monitoring. Full article

Thyroid ultrasonography (US) usage has risen significantly over the past two decades, with annual increases of up to 21% in some healthcare systems. This review examines patterns in thyroid US usage, factors driving potential misuse, and strategies to mitigate overuse. While thyroid US provides valuable information on thyroid morphology and structure without radiation exposure, inappropriate use—estimated at 10–50% of exams—leads to adverse consequences, including patient anxiety, unnecessary procedures, and potential overdiagnosis of thyroid cancer. The widespread adoption of US has coincided with increased thyroid cancer diagnoses, yet mortality rates remain unchanged, suggesting overdiagnosis rather than actual disease increase. Clinical guidelines consistently recommend selective US use not for routine evaluation of thyroid dysfunction (hyper/hypothyroidism) without palpable abnormalities, but for the anatomical assessment of palpable nodules. For thyroid incidentalomas (ITNs), evidence suggests negligible malignancy risk for nodules < 1 cm, arguing against further investigation. The paper proposes a rational approach to thyroid US, emphasizing that patients with thyroid dysfunction without palpable abnormalities, euthyroid patients without palpable nodules, and patients with subcentimetric ITNs should not undergo thyroid US. Addressing this overutilization requires a better understanding of contributing factors and targeted interventions. By restricting US to appropriate clinical scenarios, healthcare resources can be optimized without compromising patient outcomes, ensuring that rare cases of clinically significant thyroid cancer receive proper diagnosis and treatment. Full article

The fundus manifestations of pseudopapilledema closely resemble those of optic disc edema, making their differentiation particularly challenging in certain clinical situations. However, rapid and accurate diagnosis is crucial for alleviating patient anxiety and guiding treatment strategies. This study proposes an efficient low-complexity hybrid model, WHA-Net, which innovatively integrates three core modules to achieve precise auxiliary diagnosis of pseudopapilledema. First, the wavelet convolution (WTC) block is introduced to enhance the model’s characterization capability for vessel and optic disc edge details in fundus images through 2D wavelet transform and deep convolution. Additionally, the hybrid attention inverted residual (HAIR) block is incorporated to extract critical features such as vascular morphology, hemorrhages, and exudates. Finally, the Agent-MViT module effectively captures the continuity features of optic disc contours and retinal vessels in fundus images while reducing the computational complexity of traditional Transformers. The model was trained and evaluated on a dataset of 1793 rigorously curated fundus images, comprising 895 normal optic discs, 485 optic disc edema (ODE), and 413 pseudopapilledema (PPE) cases. On the test set, the model achieved outstanding performance, with 97.79% accuracy, 95.55% precision, 95.69% recall, and 98.53% specificity. Comparative experiments confirm the superiority of WHA-Net in classification tasks, while ablation studies validate the effectiveness and rationality of each module’s combined design. This research provides a clinically valuable solution for the automated differential diagnosis of pseudopapilledema, with both computational efficiency and diagnostic reliability. Full article

Early recognition and rapid appropriate antimicrobial treatment is essential for survival of sepsis. To date, it is unclear which sepsis score should be used for an early diagnosis in calves. The objective of this study was to evaluate two existing scores (Trefz and Fecteau), three novel calf sepsis screening models (CSS, CSS_A, CSS_B), and blood culture as diagnostic test for sepsis, using Bayesian latent class evaluation. A total of 131 sick calves were included in this study. Sepsis prevalence was 45%, 27%, 56%, 47%, and 55%, when using the Trefz score, Fecteau score, CSS, CSS_A, and CSS_B, respectively, and 22% had a relevant positive blood culture. The newly established models CSS (including ≥2 SIRS-criteria and abnormal mental state) and CSS_B (alternative model CSS for practice, substituting abnormal leukocyte count with mucosae) had the highest sensitivity, with 86% and 84%, respectively, and could be interesting screening tests for sepsis. Sensitivity of the existing Trefz and Fecteau score was 70% and 35–39%, respectively. The presented new sepsis scoring systems have potential as screening tests to identify calves at risk, after which a calf-side diagnostic test is advised to confirm the diagnosis. Its use might aid in the rationalization of antimicrobial use in critically ill calves. Full article

Tuberculosis (TB) remains a major cause of ill health and one of the leading causes of death worldwide, with about 1.25 million deaths estimated in 2023. Control measures have focused principally on early diagnosis, the treatment of active TB, and vaccination. However, the widespread emergence of anti-tuberculosis drug resistance remains the major public health threat to progress made in global TB care and control. Moreover, the Bacillus Calmette–Guérin (BCG) vaccine, the only licensed vaccine against TB in children, has been in use for over a century, and there have been considerable debates concerning its effectiveness in TB control. A multi-epitope vaccine against TB would be an invaluable tool to attain the Global Plan to End TB 2023–2030 target. A rational approach that combines several B-cell and T-cell epitopes from key lipoproteins was adopted to design a novel multi-epitope vaccine candidate. In addition, interactions with TLR4 were implemented to assess its ability to elicit an innate immune response. The conservation of the selected proteins suggests the possibility of cross-protection in line with the One Health approach to disease control. The vaccine candidate was predicted to be both antigenic and immunogenic, and immune simulation analyses demonstrated its ability to elicit both humoral and cellular immune responses. Protein–protein docking and normal-mode analyses of the vaccine candidate with TLR4 predicted efficient binding and stable interaction. This study provides a promising One Health approach for the design of multi-epitope vaccines against human and livestock tuberculosis. Overall, the designed vaccine candidate demonstrated immunogenicity and safety features that warrant further experimental validation in vitro and in vivo. Full article

To address the difficulty in extracting fault features from dual-channel signals, this work proposes a multichannel signal fusion processing method based on Flexible Tensor Singular Spectrum Decomposition (FTSSD) with adaptive embedding dimension selection. Firstly, the optimal embedding dimension of the trajectory tensor is adaptively determined using the proposed Trajectory Dimension Ratio (TDR) index. Once the optimal embedding dimension is obtained, the multichannel signals are represented as an optimal trajectory tensor. Then, FTSSD is employed to decompose the tensor and extract feature component signals. Moreover, by setting a residual threshold or maximum number of components to control the iterative process, the precision and rationality of the decomposition are ensured. Finally, all component signals are reconstructed, and their waveforms and spectra are comprehensively analyzed. The experimental results demonstrate that the proposed adaptive embedding FTSSD algorithm achieves a high accuracy and robustness in multichannel signal decomposition and feature extraction, making it suitable for the multicomponent analysis of complex dynamic signals such as mechanical fault diagnosis and vibration analysis. Full article

Background/Objectives: Inexperienced dentists and dental students are especially prone to misdiagnosis, and this represents a huge problem regarding antimicrobial stewardship. We aimed to develop a mobile app for rational antibiotic prescribing in dentistry based on local–systemic symptoms and patient factors, rather than solely on diagnosis, to tackle misdiagnosis. Methods: The study involved 64 participants, 50 of which were third-year dental students attending a pharmacology course focusing on antimicrobials, comprising lectures and practical sessions without (noAPP group, n = 22) or with (APP group n = 28) the assistance of a mobile application. The other 14 participants were practicing dentists who decided to register and use the application. All registered users of the application were asked to take a feedback survey, while learning outcomes were evaluated via a pharmacology quiz. Results: A decision tree was used for application development. In total, 76 impressions were collected on the application. The majority of the impressions were related to odontogenic–endodontic infections. Multiple linear regression analysis did not reveal differences in survey responses between practicing dentists and undergraduate students in the feedback survey responses. There was a significant difference in the mean pharmacology test scores between the noAPP and APP groups (5.50 ± 1.80 vs. 7.21 ± 1.03, p = 0.0001). Conclusions: The dentalantibiotic.com application was developed to support rational antibiotic prescribing, in view of tackling misdiagnosis, among inexperienced dentists, as well as to assist in undergraduates’ pharmacology learning, and the current study shows its large impact as an educational tool. The majority of participants considered it easy to use, efficient in facilitating the right antibiotic choice, and useful for everyday decision-making. Full article