Feed aggregator

Br J Nurs. 2025 Apr 17;34(8):434-435. doi: 10.12968/bjon.2025.0097.

NO ABSTRACT

PMID:40257091 | DOI:10.12968/bjon.2025.0097

Sci Total Environ. 2025 Apr 17;978:179447. doi: 10.1016/j.scitotenv.2025.179447. Online ahead of print.

ABSTRACT

The invasion of foreign species into ecosystems is a growing human-induced problem. Global warming is expected to magnify the problem by facilitating invasions and amplifying the ecological impact of invaders. We investigated if rising water temperature influences the impact of an invading shrimp Palaemon elegans on the reproductive success of a native fish, the threespine stickleback Gasterosteus aculeatus. Using a 2 × 2 factorial design, we found the shrimp to reduce the probability that stickleback males built a nest, defended it against a perceived intruder, courted females and gained matings. This reduced the number of offspring they produced, independently of temperature. Males lost more weight in the presence of the shrimp, which indicates that the shrimp can reduce the number of breeding cycles that males can complete. Thus, the shrimp has both direct negative effects and the potential for indirect delayed effects. The impact of the shrimp on stickleback reproduction overrode that of warming, most likely because the stickleback has adapted to temperature fluctuations in shallow coastal waters, but not to a high abundance of the non-native shrimp. Interestingly, the shrimp did not reduce egg hatching success, which indicates that the stickleback overestimates the risk posed by the invader. Refraining from reproduction in the presence of shrimp may have been an adaptive strategy in the past, but not in the current environment where shrimp-free habitats may no longer be found. Thus, the past reaction norm - to avoid nesting in the presence of shrimp - may have become an 'evolutionary trap'. These results emphasise the immediate threat that invading species can pose, which can be larger than the impact of warming, and stresses the importance of controlling their invasions.

PMID:40250225 | DOI:10.1016/j.scitotenv.2025.179447

Transpl Int. 2025 Apr 2;38:14268. doi: 10.3389/ti.2025.14268. eCollection 2025.

ABSTRACT

Normothermic machine perfusion (NMP) provides opportunity for viability assessment of donated kidneys. Diminished microvascular perfusion, despite adequate total blood flow, is a key pathophysiology in ischaemia-mediated acute kidney injury. Contrast-enhanced ultrasound (CEUS) could allow objective assessment of microvascular perfusion during renal NMP. Blood-based NMP was performed on porcine kidneys (circulatory death model) and human kidneys declined for transplant (preclinical). CEUS was performed with a contrast bolus into the NMP circuit arterial limb. Microvascular perfusion quality was quantified and z-score normalisation allowed combination of metrics and regions into an overall "CEUS-score." In porcine kidneys, inferior microvascular perfusion of cortex and medulla correlated with increased urinary NGAL (Neutrophil gelatinase-associated lipocalin) and histological DNA-fragmentation (a hallmark of apoptosis). In human kidneys, CEUS-score at 2 h was correlated with histological DNA-fragmentation (r = -0.937; P = 0.019) and predicted urinary NGAL at 24 h of NMP (r = -0.925; P = 0.024). Total renal flow was not correlated with these outcomes. An open-source web application (stingle.shinyapps.io/Time_intensity_analysis) and R package ("tican") were developed for quantitative time-intensity curve analysis. CEUS allows objective point-of-care microvascular perfusion assessment during NMP. As 2-hour CEUS-score predicts NGAL at 24 h, CEUS warrants future clinical investigation as a potential tool to assess kidney quality in assessment and reconditioning centres.

PMID:40242325 | PMC:PMC11999844 | DOI:10.3389/ti.2025.14268

Infect Dis Ther. 2025 Apr 14. doi: 10.1007/s40121-025-01151-0. Online ahead of print.

ABSTRACT

INTRODUCTION: The 20-valent pneumococcal conjugate vaccine (PCV20) was licensed for prevention of pneumococcal disease in infants and children on the basis of immunogenicity compared with PCV13. We aimed to evaluate PCV20 immunogenicity compared with PCV10 (Synflorix; PhiD-CV) because both vaccines demonstrated lower immunogenicity than PCV13. Nevertheless, PCV10 was highly effective against vaccine-serotype pneumococcal disease in post-licensure studies. Since no study has directly compared PCV20 versus PCV10, we conducted an indirect comparison.

METHODS: We conducted indirect comparisons for PCV20 versus PCV10 using data from published randomized control trials that directly compared these vaccines with PCV13 in 3 + 1 or 2 + 1 schedules. Serotype-specific immunoglobulin (Ig)G concentrations and opsonophagocytic activity (OPA) were assessed post-booster dose and post-primary series. First, geometric mean ratios (GMRs) were obtained for shared serotypes for each direct comparison against PCV13; we conducted a meta-analysis to generate pooled GMRs if data from multiple trials were available. Next, we indirectly compared relative GMRs of PCV20 versus PCV10 using PCV13 as the common comparator. In this descriptive analysis, GMRs > 1 favored PCV20 and GMR < 1 favored PCV10.

RESULTS: Meta-analyses of PCV10 versus PCV13 data found that PCV10 was less immunogenic for most of the ten shared serotypes. When indirectly compared via PCV13, the relative immunogenicity of PCV20 versus PCV10 varied by serotype. Overall, IgG responses for the ten shared serotypes were similar for both 3 + 1 and 2 + 1 schedules, both post-primary series and post-booster dose. GMRs for both IgG and OPA were close to the line of equivalence, or spread between favoring PCV20 or PCV10.

CONCLUSIONS: The comparable immunogenicity of PCV20 versus PCV10 in 2 + 1 and 3 + 1 schedules suggests that PCV20 will have similar effectiveness for the ten serotypes included in both vaccines, including for direct protection during infancy and toddler age, while also expanding serotype coverage. Effectiveness for PCV20 needs to be confirmed in post-marketing studies.

PMID:40227558 | DOI:10.1007/s40121-025-01151-0

J Can Assoc Gastroenterol. 2025 Jan 23;8(2):63-70. doi: 10.1093/jcag/gwae061. eCollection 2025 Apr.

ABSTRACT

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is performed using anaesthesia or conscious sedation, though the effectiveness, adverse events (AEs), and tolerability of each approach remain unclear. Thus, we compared these approaches prospectively.

METHODS: We performed a multi-centre prospective cohort study including patients with native papillae undergoing ERCP for biliary indications between 2018 and 2023. The primary outcome was sedation-related AEs, defined as sustained hypoxaemia or hypotension, unplanned mask ventilation or intubation, vasopressor or reversal agent use, cardiorespiratory arrest, or death. Secondary outcomes included other AEs, technical success measures, and patient-reported tolerability using a validated scale. Multivariable logistic regression was performed in addition to propensity score-matched analyses.

RESULTS: At 8 centres, a total of 3174 first-time biliary ERCPs were performed, 433 (13.6%) employing anaesthesia. Nine sedation-related AEs occurred with conscious sedation (0.3%), while 2 (0.5%) occurred with anaesthesia (odds ratio, OR, 0.35, 0.07-2.37). Only 25 (0.9%) conscious sedation-supported ERCPs were aborted due to the inability to appropriately sedate patients. There were no significant differences in other AE rates, cannulation success, time, or attempts, use of pre-cut or needle-knife access methods, or inadvertent pancreatic duct cannulation. Odds of significant patient-reported intra-procedural awareness and discomfort were both higher with conscious sedation (ORs 16.19, 4.81-54.53, and 21.25, 4.44-101.61, respectively). Propensity score-matched analyses yielded no differences in any outcome compared with primary analyses.

CONCLUSIONS: Routine biliary ERCP is equally safe and effective with conscious sedation (vs anaesthesia). Given regional resource limitations, conscious sedation is justified as a primary option for routine biliary ERCP.

PMID:40224576 | PMC:PMC11991873 | DOI:10.1093/jcag/gwae061

Orthop Traumatol Surg Res. 2025 Apr 10:104244. doi: 10.1016/j.otsr.2025.104244. Online ahead of print.

ABSTRACT

BACKGROUND: Despite being one of the main drivers of patients' satisfaction, the cosmetic appearance after posterior spinal fusion for adolescent idiopathic scoliosis (AIS) has not yet been thoroughly investigated. This study evaluated the self-perceived cosmetic outcomes following posterior spinal fusion in patients with AIS using the SRS-22 and Trunk Appearance Perception Scale (TAPS).

HYPOTHESIS: It is possible to highlight outcome differences before and after surgery, and to determine correlations between these self-image assessments and radiographic as well as implant-related parameters.

PATIENTS AND METHODS: A multicenter retrospective analysis on data prospectively collected between February 2011 and November 2021. AIS patients requiring surgery and with a 1-year follow-up were included. Pre- and postoperative radiographic data, including Cobb angle, clavicle angle, pelvic and sacral obliquity, and thoracic kyphosis, were compared with patient-reported outcomes. Statistical analyses evaluated correlations between self-image subdomains and surgical outcomes.

RESULTS: Data from 123 patients were available (101 females, 22 males). Considerable improvements in cosmetic self-perception were observed postoperatively, with both TAPS and SRS-22 r scores increasing one year after surgery. Coronal parameters such as major Cobb angle and clavicle angle were the primary drivers of preoperative self-image perception. In particular, the Cobb angle increased from 41.06 ± 33.29 ° in patients who did not perceive a back deformity to 65.86 ± 12.46 ° in patients who perceived a severe deformity (p = 0.009). Similarly, the clavicle angle increased from 0.31 ± 0.53 ° to 2.8 ± 2.49 ° (p = 0.02). Postoperative cosmetic appearance was correlated to implant density and thoracic kyphosis (T2-T5). Implant density decreased from 1.65 ± 0.3 to 1.47 ± 0.13 in patients with no perceived deformation and slight deformation of the back, respectively (p = 0.03); and from 1.65 ± 0.27 to 1.51 ± 0.15 in patients with no perceived deformation and slight deformation of the front, respectively (p = 0.04). The T2 - T5 kyphosis increased from 17.25 ± 9.36 ° to 38.72 ° (p = 0.05) in patients with poorer forward bending perception, and decreased from 26.61 ° to 19.9 ± 10.15 ° (p = 0.04) in patients with better cosmetic appearance in the SRS Q6.

DISCUSSION: Posterior fusion significantly enhances self-perceived trunk appearance in AIS patients. The coronal alignment has a more marked influence on preoperative cosmetic appearance, whereas postoperative sagittal alignment and implant density play a more critical roles in the postoperative self-image assessment.

LEVEL OF EVIDENCE: III.

PMID:40220785 | DOI:10.1016/j.otsr.2025.104244

Front Pharmacol. 2025 Mar 27;16:1367991. doi: 10.3389/fphar.2025.1367991. eCollection 2025.

ABSTRACT

INTRODUCTION: The β2-adrenoceptor (β2AR) is a class A G protein-coupled receptor (GPCR). It is therapeutically relevant in asthma and chronic obstructive pulmonary disease (COPD), where β2AR agonists relieve bronchoconstriction. The β2AR is a prototypical GPCR for structural and biophysical studies. However, the molecular basis of agonist efficacy at the β2AR is not understood. We hypothesised that the kinetics of GPCR-G protein interactions could play a role in determining ligand efficacy. By studying a range of agonists with varying efficacy, we examined the relationship between ligand-induced mini-Gs binding to the β2AR and ligand efficacy, along with the ability of individual ligands to activate the G protein in cells.

METHODS: We used NanoBRET technology to measure ligand-induced binding of purified Venus-mini-Gs to β2AR-nLuc in membrane preparations under both equilibrium and kinetic conditions. In addition, we examined the ability of these β2AR agonists to activate the heterotrimeric Gs protein, measured using the Gs-CASE protein biosensor in living cells. This assay detects a reduction in NanoBRET between the nano-luciferase (nLuc) donor on the Gα subunit and Venus acceptor on the Gγ upon Gs protein activation.

RESULTS: The 12 β2AR agonists under study revealed a broad range of ligand potency and efficacy values in the cellular Gs-CASE assays. Kinetic characterisation of mini-Gs binding to the agonist β2AR complex revealed a strong correlation between ligand efficacy values (Emax) and mini-Gs affinity (K d) and its association rate (k on). In contrast, there was no correlation between ligand efficacy and reported ligand dissociation rates (or residence times).

CONCLUSION: The association rate (k on) of the G protein to the agonist β2AR complex is directly correlated with ligand efficacy. These data support a model in which higher-efficacy agonists induce the β2AR to adopt a conformation that is more likely to recruit G protein. Conversely, these data did not support the role of agonist binding kinetics in determining the molecular basis of efficacy.

PMID:40213684 | PMC:PMC11983327 | DOI:10.3389/fphar.2025.1367991

Front Pharmacol. 2025 Mar 27;16:1367991. doi: 10.3389/fphar.2025.1367991. eCollection 2025.

ABSTRACT

INTRODUCTION: The β2-adrenoceptor (β2AR) is a class A G protein-coupled receptor (GPCR). It is therapeutically relevant in asthma and chronic obstructive pulmonary disease (COPD), where β2AR agonists relieve bronchoconstriction. The β2AR is a prototypical GPCR for structural and biophysical studies. However, the molecular basis of agonist efficacy at the β2AR is not understood. We hypothesised that the kinetics of GPCR-G protein interactions could play a role in determining ligand efficacy. By studying a range of agonists with varying efficacy, we examined the relationship between ligand-induced mini-Gs binding to the β2AR and ligand efficacy, along with the ability of individual ligands to activate the G protein in cells.

METHODS: We used NanoBRET technology to measure ligand-induced binding of purified Venus-mini-Gs to β2AR-nLuc in membrane preparations under both equilibrium and kinetic conditions. In addition, we examined the ability of these β2AR agonists to activate the heterotrimeric Gs protein, measured using the Gs-CASE protein biosensor in living cells. This assay detects a reduction in NanoBRET between the nano-luciferase (nLuc) donor on the Gα subunit and Venus acceptor on the Gγ upon Gs protein activation.

RESULTS: The 12 β2AR agonists under study revealed a broad range of ligand potency and efficacy values in the cellular Gs-CASE assays. Kinetic characterisation of mini-Gs binding to the agonist β2AR complex revealed a strong correlation between ligand efficacy values (Emax) and mini-Gs affinity (K d) and its association rate (k on). In contrast, there was no correlation between ligand efficacy and reported ligand dissociation rates (or residence times).

CONCLUSION: The association rate (k on) of the G protein to the agonist β2AR complex is directly correlated with ligand efficacy. These data support a model in which higher-efficacy agonists induce the β2AR to adopt a conformation that is more likely to recruit G protein. Conversely, these data did not support the role of agonist binding kinetics in determining the molecular basis of efficacy.

PMID:40213684 | PMC:PMC11983327 | DOI:10.3389/fphar.2025.1367991

Ann Med Surg (Lond). 2025 Mar 27;87(4):2049-2058. doi: 10.1097/MS9.0000000000003052. eCollection 2025 Apr.

ABSTRACT

Global neurosurgery has witnessed transformative developments in advocacy and policy aimed at overcoming the barriers that hinder equitable access to neurosurgical care. This paper reveals the stark disparities faced by low- and middle-income countries (LMICs) with an annual burden of 5 million affected individuals. Despite these challenges, the emergence of global neurosurgery stands as a beacon of hope, aspiring to deliver timely, safe, and affordable neurosurgical care. Advocacy and policy play pivotal roles in this endeavour, exemplified by initiatives, like National Surgical, Obstetrics, and Anesthesia Plans (NSOAPs) and Global Neurosurgery Initiatives (GNI), addressing accessibility, training, and disparities. Collaborations between diverse entities and interdisciplinary approaches gain prominence, fostering comprehensive advocacy and policy frameworks. A resolute commitment to equity is discernible, propelling policies toward universal access to neurosurgical care. However, crucial challenges, such as limited resources, awareness gaps, complex political landscapes, data deficiencies, and insufficient international collaborations, must be addressed to see the full potential of these initiatives. While challenges persist, progress is evident through collaborative efforts, technological advancements, and evolving policy landscapes, promising a trajectory toward accessible, safe, and affordable neurosurgical care for all.

PMID:40212174 | PMC:PMC11981366 | DOI:10.1097/MS9.0000000000003052

Int J Biol Macromol. 2025 Apr 8:142976. doi: 10.1016/j.ijbiomac.2025.142976. Online ahead of print.

ABSTRACT

Blend nanocomposites of chitosan (CS) and polyvinyl alcohol (PVA), reinforced with varying concentrations of nanocurcumin (NC), were synthesized using a simple green method. The impact of NC on the optical, structural, and morphological characteristics of the blend nanocomposite films was evaluated through different analytical techniques, including FT-IR, XRD, UV-Vis spectroscopy, scanning electron microscopy, TGA, universal testing machine and electrical measurements. The distinctive peaks observed in the FT-IR and XRD analysis confirmed the successful incorporation of NC into the PVA/CS (PC) blend matrix. UV spectroscopy revealed that absorption increased with nanoparticle concentration, with the 9 wt% sample showing the highest intensity, which correlates with its low optical bandgap energy. SEM analysis showed that nanoparticles influenced the surface morphology of the PC matrix, with the most uniform particle distribution observed in the 9 wt% sample. Increasing NC content improved the thermal stability of the PC films. The nanocomposite with 9 wt% NC exhibited a significant improvement in tensile strength, increasing by 35 % compared to neat PC, along with an excellent Young's modulus. The temperature-dependent dielectric constant, AC conductivity, and impedance were analyzed across different NC loadings. The maximum conductivity and dielectric constant were found in the 9 wt% nanocomposites. The superior tensile strength, Young's modulus, thermal stability, conductivity, dielectric constant, and optical properties of the PC blend nanocomposites highlight their potential for use in eco-friendly, flexible optoelectronic devices.

PMID:40210076 | DOI:10.1016/j.ijbiomac.2025.142976

Bioinformatics. 2025 Apr 10:btaf158. doi: 10.1093/bioinformatics/btaf158. Online ahead of print.

ABSTRACT

MOTIVATION: Several methods have been developed for trajectory inference in single cell studies. However, identifying relevant lineages among several celltypes and interpreting the results of downstream analysis remains a challenging task that requires deep understanding of various celltype transitions and progression patterns. Therefore, there is a need for methods that can aid researchers in the analysis and interpretation of such trajectories.

RESULTS: We developed PyEvoCell, a dashboard for trajectory interpretation and analysis that is augmented by large language model (LLM) capabilities. PyEvoCell applies the LLM to the outputs of trajectory inference methods such as Monocle3, to suggest biologically relevant lineages. Once a lineage is defined, users can conduct differential expression and functional analyses which are also interpreted by the LLM. Finally, any hypothesis or claim derived from the analysis can be validated using the veracity filter, a feature enabled by the LLM, to confirm or reject claims by providing relevant PubMed citations.

AVAILABILITY: The software is available at https://github.com/Sanofi-Public/PyEvoCell. It contains installation instructions, user manual, demo datasets, as well as license conditions (including limitation to non-commercial uses only). https://doi.org/10.5281/zenodo.15114803.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:40209077 | DOI:10.1093/bioinformatics/btaf158

J Am Chem Soc. 2025 Apr 10. doi: 10.1021/jacs.4c13473. Online ahead of print.

ABSTRACT

Parkinson's disease (PD) is linked to the aggregation of the intrinsically disordered protein α-synuclein (aSyn), but the precise triggers and mechanisms driving this process remain unclear. Local environmental factors, such as ion concentrations, can influence aSyn's conformational ensemble and its tendency to aggregate. In this study, we explore how physiologically relevant ions, mainly Ca2+ and Na+, affect aSyn aggregation, monomer structural dynamics, and fibril polymorphism. ThT fluorescence assays show that all ions speed up aggregation, with Ca2+ having the strongest effect. Using heteronuclear single quantum correlation nuclear magnetic resonance (1H-15N HSQC NMR) spectroscopy, we validate that Ca2+ binds at the C-terminus while Na+ interacts nonspecifically across the sequence. Small-angle neutron scattering (SANS) and hydrogen-deuterium exchange mass spectrometry (HDX-MS) show that Na+ leads to more extended aSyn structures, while Ca2+ results in moderate extension. Molecular dynamics (MD) simulations support this, showing Na+ increases extension between the NAC region and C-terminus, whereas Ca2+ biases the ensemble toward a moderately elongated structure. MD also shows that Ca2+ increases water persistence times in the hydration shell, indicating that aSyn aggregation propensity is due to a combination of conformational bias of the monomer and solvent mobility. Atomic force microscopy (AFM) points toward the formation of distinct fibril polymorphs under different ionic conditions, suggesting ion-induced monomer changes contribute to the diversity of fibril structures. These findings underscore the pivotal influence of the local ionic milieu in shaping the structure and aggregation propensity of aSyn, offering insights into the molecular underpinnings of PD and potential therapeutic strategies targeting aSyn dynamics.

PMID:40207671 | DOI:10.1021/jacs.4c13473

Cancer Cytopathol. 2025 May;133(5):e70014. doi: 10.1002/cncy.70014.

ABSTRACT

BACKGROUND: There is increasing interest in designing new fine-needle aspiration (FNA) needles to maximize tissue acquisition. This study compares cytological preparations from a new rotating FNA needle (CytoCore) with conventional FNA (ConvFNA) using semiquantitative evaluation and quantitative image analysis (IA).

METHODS: FNA were performed on ex vivo tissue in quadruplicate for each needle type (ConvFNA and CytoCore), including different sizes (22 G and 25 G) and variable procedure time (5 and 20 s). The Nikon Elements (v5.41.02) was used to quantify the cellularity and size of the largest tissue fragment on cell blocks.

RESULTS: A total of 96 cytology specimens were evaluated were evaluated from benign and malignant specimens. For both ConvFNA and CytoCore, a longer procedure time (20 s) tended to produce greater cellularity and larger tissue fragments in the cell block specimens for both needles when analyzed with image analysis and was statistically significant for the CytoCore needle (p < .01). The ConvFNA tended to perform better with short procedure time. There was no statistically significant difference using different needle gauges.

CONCLUSION: This study shows that IA can help to quantitatively evaluate sample cellularity in the cell blocks from specimens acquired with different needles. A longer procedure time tended to produce more cellular samples and larger tissue fragments in the cell block for both ConvFNA and CytoCore needles and was statistically significant for CytoCore. Additional larger studies, including those with true clinical cases, should be considered to evaluate the different needle types further.

PMID:40202788 | DOI:10.1002/cncy.70014

J Phys Chem C Nanomater Interfaces. 2025 Mar 21;129(13):6196-6210. doi: 10.1021/acs.jpcc.4c08116. eCollection 2025 Apr 3.

ABSTRACT

This study aims to elucidate the adsorption and surface chemistry of N-methylaniline (NMA) on Pt(111), using it as a model molecule to probe the activation mechanisms of aromatic amines on catalytic surfaces. Through a combination of density functional theory (DFT) calculations and experimental techniques such as temperature-programmed X-ray photoelectron spectroscopy (TP-XPS), temperature-programmed desorption (TPD), and Fourier transform infrared reflection absorption spectroscopy (FT-IRRAS), we explored the coverage-dependent behavior of NMA on Pt(111) to identify key steps in the activation process. The population of certain reaction paths is driven by a coverage-dependent balance between molecule surface charge transfer and intermolecular interactions, dictating the selective activation of specific bonds. Our findings reveal how coverage influences the orientation and bonding of NMA on the Pt(111) surface. At lower coverages, the molecule binds to the surface through the phenyl ring and activation, facilitating C-N bond cleavage to the ring under HCN formation. In comparison, at higher coverages, the molecule binds only through the nitrogen atom and desorbs intact. These insights into variable bond activation lay the groundwork for understanding the fundamental processes involved in potential heterogeneously catalyzed reactions of aromatic amines, contributing to the development of new catalytic strategies.

PMID:40201732 | PMC:PMC11973917 | DOI:10.1021/acs.jpcc.4c08116

ACS Synth Biol. 2025 Apr 8. doi: 10.1021/acssynbio.4c00704. Online ahead of print.

ABSTRACT

Natural biological systems use feedback regulation to effectively respond and adapt to their changing environment. Even though in engineered systems we understand how accurate feedback can be depending on the electronic or mechanical parts that it is implemented with, we largely lack a similar theoretical framework to study feedback regulation in biological systems. Specifically, it is not fully understood or quantified how accurate or robust the implementation of biological feedback actually is. In this paper, we study the sensitivity of biological feedback to variations in biochemical parameters using five example circuits: positive autoregulation, negative autoregulation, double-positive feedback, positive-negative feedback, and double-negative feedback (the toggle switch). We find that some of these examples of biological feedback are subjected to fundamental performance trade-offs, and we propose multi-objective optimization as a framework to study their properties. The impact of this work is to improve robust circuit design for synthetic biology and to improve our understanding of feedback for systems biology.

PMID:40198741 | DOI:10.1021/acssynbio.4c00704

JAMA Netw Open. 2025 Apr 1;8(4):e253910. doi: 10.1001/jamanetworkopen.2025.3910.

ABSTRACT

IMPORTANCE: India accounts for more than one-third of oral cancer (OC) cases globally. Cancer survival measures the effectiveness of the health care system's cancer control efforts and the proportion of people who survive during a specified time.

OBJECTIVE: To estimate the 5-year survival rates among patients with OC diagnosed in India and assess the association of survival with age, place of residence, histologic type, and clinical extent of OC.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study evaluated survival of patients diagnosed with primary OC (International Classification of Diseases for Oncology, Third Revision, codes C01-C06) between January 1, 2012, and December 31, 2015, and followed up until June 30, 2021. Patients were included from 10 population-based cancer registries (PBCRs). Data were analyzed between March 15 and August 20, 2024.

EXPOSURES: Demographic factors (patient age, sex, and place of residence) and disease factors (clinical extent of disease and histologic type).

MAIN OUTCOMES AND MEASURES: The main outcome was 5-year age-standardized relative survival (ASRS) for OC among male and female patients. A multivariable Cox proportional hazards model estimated hazard ratio (HR) and 95% CI, adjusting for covariates.

RESULTS: Data from the 10 PBCRs encompassed 14 059 patients of all ages (median age, 55 [IQR, 45-65] years; 10 380 male [73.8%]) diagnosed with OC. The overall 5-year ASRS rate for OC was 37.2% (range, 20.9%-58.4%). The estimated ASRS rates at 5 years were 36.0% (range, 20.7%-59.3%) for male and 39.6% (range, 21.4%-54.8%) for female patients. Ahmedabad urban had the highest 5-year ASRS at 58.4% (95% CI, 56.3%-60.4%) for both sexes, while Manipur had the lowest rates at 20.9% (95% CI, 14.9%-27.6%). Survival rates differed significantly between rural areas (34.1%; 95% CI, 31.4%-36.9%) and urban areas (48.5%; 95% CI, 47.4%-49.7%). Pooled data from Kollam and Thiruvananthapuram revealed that individuals 65 years or older (HR, 1.76; 95% CI, 1.44-2.14) and those with distant metastasis (HR, 3.95; 95% CI, 2.78-5.60) had a significantly higher risk of death.

CONCLUSIONS AND RELEVANCE: In this cohort study from India, significant survival disparities were observed among patients with OC based on demographic factors and clinical characteristics. Survival rates were lower in rural areas compared with urban regions, underscoring the inequalities in quality of care and services and emphasizing the need to improve OC survival rates in India.

PMID:40198071 | DOI:10.1001/jamanetworkopen.2025.3910

Immunotargets Ther. 2025 Apr 3;14:339-357. doi: 10.2147/ITT.S495751. eCollection 2025.

ABSTRACT

While immunotherapy has transformed treatment across various cancers, its impact on breast cancer is relatively limited. Recent advances have established immunotherapy as an effective approach for triple-negative breast cancer (TNBC), an aggressive subtype with limited therapeutic targets and poor prognosis. Specifically, pembrolizumab, an immune checkpoint inhibitor (ICI), is now approved for both first-line metastatic and early-stage TNBC. In metastatic TNBC, combining ICIs with chemotherapy, particularly pembrolizumab, has demonstrated survival benefits in patients with PD-L1-positive disease. However, extending these benefits to broader populations has proven challenging, highlighting the need for better patient selection and novel strategies. Emerging approaches include combining ICIs with antibody-drug conjugates, PARP inhibitors, dual ICIs, and bispecific antibodies targeting angiogenesis and immune checkpoints. These strategies aim to overcome resistance and expand immunotherapy's efficacy beyond the PD-1/PD-L1 pathway. In early-stage disease, pembrolizumab combined with chemotherapy in the neoadjuvant setting has significantly improved pathologic complete response, event-free survival, and overall survival, establishing a new standard of care. Ongoing research aims to determine the optimal timing for ICI administration, explore less toxic chemotherapy backbones, utilize biomarkers for personalized treatment, and assess whether adding complementary treatments, such as radiation therapy for high-risk cases, can improve outcomes. This review examines the successes and setbacks of ICI use in TNBC, offering a comprehensive overview of current practices and future directions. It emphasizes optimizing ICI timing, leveraging biomarkers, and integrating novel agents to refine treatment approaches for both metastatic and early-stage TNBC. As immunotherapy continues to evolve, future research must address the unmet needs of this challenging breast cancer subtype, offering hope for improved outcomes.

PMID:40196378 | PMC:PMC11974553 | DOI:10.2147/ITT.S495751

Eur J Med Res. 2025 Apr 7;30(1):251. doi: 10.1186/s40001-025-02483-w.

ABSTRACT

Three-dimensional printing (3DP) has emerged as a transformative technology in the field of central nervous system (CNS) tumours, offering innovative advancements in various aspects of diagnosis, treatment and education. By precisely replicating the microenvironment of CNS tumours, modelling tumour vascularisation, and capturing genetic heterogeneity, 3DP enables the development of targeted therapies and personalised treatment strategies. The technology has markedly enhanced preoperative planning and intraoperative guidance, providing highly accurate, patient-specific models that improve tumour localisation, facilitate tailored surgical planning, and offer superior visualisation of complex anatomical structures. Furthermore, 3DP has revolutionised education and training for neurosurgeons, trainees, and patients by delivering realistic simulations that enhance surgical skills and decision-making. Despite its transformative potential, the widespread adoption of 3DP faces challenges, including material biocompatibility issues, high costs, and technical limitations. Furthermore, the ethical and regulatory landscape for 3DP in clinical practice requires further development. This review concludes that while 3DP offers significant promise for advancing CNS tumour treatment, ongoing research is essential to address these challenges and optimising its clinical impact.

PMID:40189551 | DOI:10.1186/s40001-025-02483-w

Methods Mol Biol. 2025;2901:103-115. doi: 10.1007/978-1-0716-4394-5_8.

ABSTRACT

DNA origami nanostructures offer wide potential for controlled functionalization with molecules of interest, such as peptides, enzymes, small-molecule drugs, and fluorophores. Here, we describe a protocol for the synthesis and characterization of aptamer-modified DNA origami nanostructures that can act as a vehicle for delivering antimicrobials to Gram-positive and Gram-negative bacterial targets in a specific and efficient manner.

PMID:40175870 | DOI:10.1007/978-1-0716-4394-5_8

Methods Mol Biol. 2025;2901:103-115. doi: 10.1007/978-1-0716-4394-5_8.

ABSTRACT

DNA origami nanostructures offer wide potential for controlled functionalization with molecules of interest, such as peptides, enzymes, small-molecule drugs, and fluorophores. Here, we describe a protocol for the synthesis and characterization of aptamer-modified DNA origami nanostructures that can act as a vehicle for delivering antimicrobials to Gram-positive and Gram-negative bacterial targets in a specific and efficient manner.

PMID:40175870 | DOI:10.1007/978-1-0716-4394-5_8