Immunonutrition examines how diet influences immune development. Complementary feeding represents a critical window for long-term health. We aimed to map evidence linking complementary feeding to immune outcomes, allergy, infection, and growth in infants and toddlers (≤ 3 years). We conducted a scoping review and evidence-gap mapping, following PRISMA-ScR. MEDLINE and Epistemonikos were searched from inception to November 2024. Concepts included diet diversity/patterns, feeding practices/models, and timing of allergen introduction, timing of complementary feeding, macronutrients, micronutrients, foods, supplementation, and ultra-processed foods. We included systematic reviews and recent primary studies meeting criteria. From 13,512 records screened, 108 systematic reviews were included, comprising 99 randomized controlled trials, 41 cohorts, 22 case-control, and 14 cross-sectional studies. Most reviews addressed nutrient intake, supplementation, or timing of allergen introduction, while fewer reviews explored diet diversity, foods, or ultra-processed food intake. Responsive complementary feeding was consistently associated with healthier growth and lower obesity risk, whereas restrictive practices showed adverse effects. Greater diet diversity was linked to reduced asthma and food allergy risk, though eczema findings were inconsistent. Western-style diets high in processed foods, fat, sugar, and meat correlated with higher allergy risk, while home-prepared diets were protective. Micronutrient supplementation (iron, zinc, vitamin D) reduced infection and anemia risk but had mixed effects on allergy. Early allergen introduction reduced food allergy incidence. Complementary feeding research now extends beyond calorie counting, macronutrients, and early allergen introduction to dietary patterns and early life nutrition that supports the microbiome. Evidence supports dietary diversity, timely food allergen introduction, and responsive feeding, while discouraging restrictive practices and ultra-processed foods. Future work should harmonize definitions and investigate plant-based diets, advanced glycation end products, and processed food exposures.
Chronic kidney disease (CKD) is a major clinical challenge because it leads to irreversible nephron loss and limited endogenous repair. Here, we developed a bioactive hybrid scaffold composed of PLGA, magnesium hydroxide (MH), extracellular matrix (ECM) components, zinc oxide, lactoferrin, and nicotinamide loaded liposome (LNP) and extracellular vesicles (EVs) hybrid nanoparticles (hEV) complexes (PMEZL/hEV) to promote renal repair by integrating PI3K-AKT signaling with complementary pro-survival pathways. In a 5/6 nephrectomy model, scaffold implantation significantly attenuated inflammation and oxidative stress. qPCR analyses showed suppressed NF-κB and TNF-α levels with increased expression of Nephrin, Podocin, IL-4, IL-10, SOD, and Sirt-1 at 2 weeks, which became further pronounced at 8 weeks in the PMEZL/hEV group. Western blot analysis demonstrated marked activation of p-AKT and lower levels of caspase 9 and cleaved caspase 3, indicating inhibition of apoptotic signaling. Importantly, cytoprotective effects were partially preserved under PI3K-AKT inhibition, suggesting engagement of complementary PI3K-AKT independent survival mechanisms. Concurrent downregulation of PAI-1 suggested suppression of fibrotic remodeling. Immunohistochemistry confirmed progressive restoration of Synaptopodin and PAX2, supporting podocyte recovery and tubular regeneration. Histological analyses revealed decreased fibrosis and increased glomerular density across scaffold implanted groups, with the greatest improvements in kidneys implanted with the PMEZL/hEV scaffold. Functional measurements showed a reduction in serum blood urea nitrogen (BUN), creatinine, C-reactive protein, and cystatin C, with significant improvements by 8 weeks. Collectively, the multifunctional hybrid scaffold orchestrates anti-inflammatory, antioxidative, antiapoptotic, and pro-regenerative responses through coordinated multimodal survival signaling, leading to substantial restoration of kidney structure and function in CKD.
MRI and magnetic resonance cholangiopancreatography (MRCP) remain foundational techniques for the evaluation of pancreatobiliary disease because they provide a comprehensive, non-invasive assessment of the pancreatic parenchyma, biliary tree and surrounding structures. With optimized protocols, MRI/MRCP has high diagnostic performance for biliary obstruction, pancreatic cystic lesions and many inflammatory or neoplastic pancreatic disorders. Nevertheless, selected clinical scenarios remain challenging when findings are equivocal, discordant with biochemical or clinical suspicion, or insufficient to guide intervention. Endoscopic ultrasound (EUS) should therefore be understood not as a replacement for MRI/MRCP, but as a complementary problem-solving modality. Its incremental value is greatest when a specific unresolved question remains after cross-sectional imaging and when the result is likely to change management. Beyond high-resolution proximity-based imaging, EUS can provide tissue acquisition, cyst fluid analysis, molecular testing, contrast-enhanced assessment, elastography and selected therapeutic interventions. This revised review defines the complementary roles of MRI/MRCP and EUS in pancreatobiliary disease, with emphasis on small solid pancreatic lesions, pancreatic cystic lesions, pancreaticobiliary microlithiasis, autoimmune pancreatitis mimics, and therapeutic EUS applications. We also discuss MRI/MRCP protocol optimization, emerging deep learning-based MRI reconstruction, and the limitations of EUS in altered anatomy, gastric outlet obstruction, pancreatic tail lesions and multifocal neuroendocrine tumors. A practical selective imaging pathway is proposed to support clinically driven decision-making.
The cement industry contributes approximately 7-8% of global anthropogenic CO2 emissions, yet accurate cradle-to-gate embodied carbon estimation requires plant-level inventory data that are largely unavailable across developing and emerging economies. This data scarcity constrains global benchmarking and the implementation of emerging embodied carbon regulations. This study proposes a STIRPAT-grounded hybrid machine learning-life cycle assessment (ML-LCA) framework for estimating national-scale cement embodied carbon using exclusively publicly available macroeconomic data. GDP per capita, population, and temporal indicators are used to predict the clinker-to-cement ratio (CCR), which is subsequently propagated through a technology-stratified, process-based LCA model enforcing stoichiometric and thermodynamic constraints across A1-A3 stages. Among seven candidate algorithms, Gradient Boosting was selected for its smooth non-linear approximation and LCA integration suitability. SHAP analysis confirms GDP per capita as the dominant CCR driver, with contributions directionally consistent with established technology diffusion theory, ensuring model transparency. Validation across 18 economies through statistical metrics, residual diagnostics, country-level diagnostic benchmarking, Leave-One-Country-Out (LOCO) cross-validation, and three independent literature-benchmarking countries (Pakistan, Mexico, Spain) confirms physically plausible and externally consistent outputs ranging from 0.53 to 0.97 kg CO2/kg cement. A central methodological contribution is the ability to estimate the clinker-substitution decoupling effect at the country scale using only macroeconomic inputs, in contexts where plant-level LCA inventory data are unavailable. Conventional LCA already separates process, energy, and material composition contributions when inventory data are present; the present framework extends this separation to data-scarce national contexts. At the system level, an Environmental Kuznets Curve-type pattern is qualitatively reproduced when model outputs are aggregated across countries, providing a coherence check on the framework as a whole. Out-of-country generalisation is assessed using Leave-One-Country-Out (LOCO) cross-validation as the primary protocol (mean fold RMSE 0.077; 12 of 18 folds below RMSE 0.10), with a forward-chaining temporal split as a complementary diagnostic. The framework is operationalised through an interactive decision-support interface, offering a scalable, transparent baseline for embodied carbon benchmarking, policy screening, and net-zero pathway evaluation in the global cement sector. The framework is positioned as a screening-level reference for data-scarce contexts, complementary to plant-level LCA and Environmental Product Declarations where these are available.
Understanding long-term physical changes in lyophilized matrices is essential for rational formulation design and stability assessment. In this study, positron annihilation lifetime spectroscopy (PALS) was applied to monitor time-dependent structural evolution in simple lyophilized carbohydrate-polymer matrices stored for up to 21 months under low and elevated humidity conditions. Formulations containing saccharides, polyols and starch were selected as model amorphous systems to investigate molecular mobility and phase evolution in the absence of active pharmaceutical ingredients. The free volume and ortho-positronium (o-Ps) intensity were determined as complementary indicators of free volume within the amorphous phase and relative amorphous fraction, respectively. Over prolonged storage, composition- and humidity-dependent changes in these parameters were observed. Under elevated humidity, selected formulations exhibited reductions in o-Ps intensity consistent with partial recrystallization, while variations in free volume reflected concurrent structural relaxation within the remaining amorphous phase. Solid-state 1H NMR and X-ray diffraction provided complementary support for these evolution trends. The results demonstrate that PALS sensitively detects physical aging and structural changes in lyophilized matrices by probing free-volume evolution during storage. These findings support the utility of PALS as a non-destructive analytical tool for monitoring long-term physical stability of amorphous lyophilized matrices under defined environmental conditions.
Total hip arthroplasty is the surgical treatment of choice to improve the quality of life of patients with advanced osteoarthritis. This treatment aims to increase functional capacity and reduce pain. However, anxiety is one of the most frequently described uncomfortable experiences associated with this surgery. Although there has been extensive study of techniques to treat preoperative anxiety, little is known about interventions targeted at reducing postoperative anxiety associated with the fear and uncertainty of adjusting to life changes after surgery. To conduct a systematic review of the literature to identify the non-pharmacological interventions that have been performed to reduce postoperative anxiety in patients undergoing hip arthroplasty and their effectiveness. A bibliographic search was conducted in Pubmed, Scopus, and Web of Science until April 2026. Search was based on the following selection criteria: randomized clinical trials, quasi-experimental pre-post studies with or without control groups. Study selection and data analysis were conducted according to the predefined eligibility criteria and analytical approach, and the reporting was conducted according to the PRISMA 2020 guidelines. Risk of bias was assessed using the Cochrane Risk of Bias tool (RoB 2) for randomized controlled trials and ROBINS-I for non-randomized studies. Included studies assessed technology-assisted interventions (immersive virtual reality, telemedicine, and video-based health education), nursing-led educational or behavioral programs (including self-efficacy-enhancing and continuous nursing care models), multimodal rehabilitation-based approaches, and complementary therapies such as aromatherapy. Overall, the most consistent reductions in anxiety were observed in studies evaluating immersive virtual reality and self-efficacy-enhancing interventions. Nursing-led and continuous care models also reported improvements, although findings were more variable. Educational and eHealth-based approaches showed benefits primarily in the short term. Telemedicine and aromatherapy demonstrated limited or inconsistent effects on anxiety. Substantial heterogeneity in interventions, outcome measures, and follow-up periods precluded quantitative synthesis; therefore, a structured narrative synthesis was performed. Multicomponent nursing-led and technology-assisted interventions, particularly immersive virtual reality and self-efficacy-based programs, show the most consistent evidence for reducing postoperative anxiety following THA. Educational and eHealth-based interventions demonstrate short-term benefits, whereas telemedicine and complementary approaches such as aromatherapy show more limited or inconsistent effects. However, the overall evidence base remains heterogeneous and methodologically variable. Future research should prioritise adequately powered, multicentre trials with standardised outcome measures and longer follow-up periods.
Variants of uncertain significance (VUS) in BRCA2 remain a major challenge in the clinical management of breast cancer, particularly in Asian populations where population-specific reference data are limited. Functional assays may provide complementary biological evidence to support interpretation of these variants. Three BRCA2 missense VUS-c.5969 A > C (p.Asp1990Ala), c.3671G > A (p.Gly1224Asp), and c.5459G > A (p.Cys1820Tyr)-were selected based on their frequency in Korean cohorts and/or strong family history of breast cancer. Full-length BRCA2 constructs harboring each variant were introduced into BRCA2-knockout DLD-1 cells. Functional consequences were evaluated using cellular sensitivity assays following cisplatin treatment and ionizing radiation, response to the PARP inhibitor olaparib, and homologous recombination (HR) efficiency assessed by a GFP-based reporter system. Cells expressing BRCA2 p.Asp1990Ala consistently demonstrated increased sensitivity to cisplatin, ionizing radiation, and olaparib, comparable to pathogenic controls. In addition, GFP-based HR assays revealed a marked reduction in HR repair efficiency in p.Asp1990Ala-expressing cells. In contrast, cells expressing BRCA2 p.Gly1224Asp or p.Cys1820Tyr exhibited DNA damage responses, drug sensitivity profiles, and HR activity similar to wild-type BRCA2 across all assays. Among the three BRCA2 VUS analyzed, p.Asp1990Ala exhibited a pathogenic-like functional phenotype characterized by impaired homologous recombination repair, whereas p.Gly1224Asp and p.Cys1820Tyr appeared functionally neutral. These findings highlight the functional heterogeneity of BRCA2 VUS and support the role of functional assays as complementary tools for variant interpretation in breast cancer.
Phytochromes are red/far-red light photoreceptors that regulate diverse aspects of plant photomorphogenesis. Among angiosperm phytochromes, phytochrome C (phyC) is the least well characterized, despite its conservation across monocots and dicots. Previous studies have suggested that phyC exhibits absorption properties distinct from those of phyA and phyB, but the physiological significance of these differences has remained unclear. Here, we show that the photosensory module of phyC exhibits a hypsochromically shifted Pr absorption maximum that is conserved across monocots and dicots. This spectral property is primarily determined by the GAF domain rather than by individual amino acid substitutions. Physiological analyses revealed that phyC contributes to the inhibition of hypocotyl elongation under red light conditions lacking shorter wavelength components, whereas its contribution is limited under white light conditions. These findings indicate that the hypsochromic shift in phyC provides a complementary mechanism for phytochrome signaling under specific light environments. Spectral overlap analysis further indicated that the hypsochromically shifted Pr absorption of phyC enhances photon capture under both direct sunlight and leaf-filtered light, although the magnitude of this effect is modest. Together, these findings indicate that the conserved hypsochromic shift in Pr absorption of phyC provides a complementary, context-dependent mechanism for phytochrome signaling, particularly under light environments in which phyB-mediated responses are less effective.
Type 2 diabetes mellitus (T2DM) is escalating worldwide and remains difficult to control durably, in part because progressive β-cell dysfunction undermines many therapies and because long-term management must balance efficacy, safety, and affordability. Recent decades have shown that targeting sodium-glucose cotransporters (SGLTs) especially renal SGLT2 can reduce glucose levels independently of insulin and, crucially, deliver cardio-renal benefits that extend beyond glycaemic control. Yet, despite the clinical success of synthetic "gliflozins", gaps remain, adverse events, incomplete inhibition of renal glucose reabsorption, and limited access in some health systems. This review focuses on two quercetin glycosides quercetin-3-O-glucoside (isoquercitrin) and quercetin-3-O-rutinoside (rutin) as potential SGLT-focused modulators. This study employed a narrative mechanistic review approach integrating published experimental evidence, physicochemical structure-activity relationship (SAR) analysis, and exploratory molecular docking to examine potential SGLT-related interactions and complementary glucose-regulatory pathways of Q3G and rutin. We synthesise mechanistic evidence suggesting that Q3G and rutin may modulate SGLT-related pathways through intestinal SGLT1 interaction, regulation of renal SGLT2 expression, and complementary glucose-regulatory mechanisms. However, direct inhibition of human SGLT2 transport activity has not yet been experimentally demonstrated, and current evidence predominantly may indicate indirect pathway modulation rather than gliflozin-like transporter inhibition. Contradictory findings across assay systems are discussed in relation to structure-activity relationships shaped by glycosylation. We further examine pharmacokinetics, tissue exposure plausibility, and translational feasibility, and propose a stepwise development roadmap emphasising transporter-specific assays, quantitative target engagement, and clinically meaningful biomarkers. Q3G and rutin may exhibit putative SGLT-relevant activity within a broader polypharmacological framework; however, direct transporter-specific inhibition and clinically relevant renal exposure remain to be established through future functional and translational studies.
Accurate wave-optical simulation in electron microscopy is severely constrained by the extreme sampling requirements imposed by short wavelengths and relatively large convergence angles. Conventional implementations of the angular spectrum method (ASM) rapidly become computationally intractable, often exceeding realistic memory and time limits. We present two numerical approaches - the scaling angular spectrum method (SASM) and the no-lensing angular spectrum method (NLASM) - that systematically reduce the sampling requirements while retaining the essential physics of wave propagation. SASM replaces the original optical system with a scaled equivalent in which lens-induced beam convergence or divergence is reduced, lowering memory usage and computational cost by approximately the square of the scaling factor. NLASM suppresses lensing effects altogether, enabling highly efficient propagation away from focal planes. Benchmarking against the Bluestein (chirp-z) transform reveals that the three methods are complementary and together enable wave-optical simulations of complex electron-optical systems previously considered infeasible. These results establish practical pathways towards routine wave-based modelling in electron microscope design.
Diffuse gliomas remain among the most surgically challenging tumors, characterized by their infiltrative nature, proximity to eloquent brain structures, and the formidable barrier posed by the BBB to systemic therapeutic delivery. Maximizing extent of resection (EOR) while preserving neurological function remains a central determinant of survival and quality of life, and the iterative integration of intraoperative technologies into surgical practice has become essential to achieving this balance. We performed a comprehensive narrative review of established and emerging intraoperative technologies for glioma surgery, organized around two clinical imperatives: optimizing tumor delineation and safe resection, and enhancing local therapeutic delivery. Awake craniotomy with direct electrical stimulation remains the gold standard for preserving eloquent cortex and subcortical tracts, consistently reducing postoperative neurological deficits while increasing gross total resection rates. Fluorescence-guided surgery with 5-ALA and fluorescein enhances real-time tumor margin visualization, and their combined use achieves greater EOR than either agent alone. Intraoperative MRI compensates for progressive brain shift and, when used alongside 5-ALA, provides the strongest currently available platform for maximizing safe resection. Augmented reality navigation further enhances spatial orientation by overlaying 3D virtual anatomy directly onto the operative field. Emerging tissue characterization tools, including stimulated Raman histology, confocal laser endomicroscopy, and AI-based platforms such as FastGlioma and DeepGlioma, enable rapid intraoperative molecular diagnosis without the delays of conventional frozen section pathology. For therapeutic delivery, low-frequency focused ultrasound and convection-enhanced delivery bypass the BBB to achieve high local drug concentrations, while endovascular intra-arterial infusion enables targeted delivery across the tumor vascular territory. Photodynamic and sonodynamic therapy generate localized cytotoxic effects within the resection cavity at the time of surgery. Intraoperative brachytherapy with Cesium-131 tile implants delivers conformal radiation at the time of resection and may potentiate antitumor immunity. Laser interstitial thermal therapy combines cytoreduction with sustained BBB disruption, creating a therapeutic window for otherwise CNS-impermeant agents including checkpoint inhibitors. The deliberate integration of these complementary modalities into a phase-organized intraoperative workflow, spanning preoperative planning, real-time resection guidance, intraoperative margin and tissue assessment, and post-resection locoregional therapeutic delivery, defines the emerging paradigm of precision glioma surgery. Realizing the full potential of this framework will require prospective validation of combinatorial strategies, standardization of technology integration protocols, and rigorous evaluation of neurological and oncological outcomes.
LGBTQA+ people are at greater risk of using cannabis at earlier ages, in greater frequencies and quantities and over longer periods of time compared with their cisgendered, heterosexual peers. Prescribed medicinal cannabis is becoming increasingly commonly utilised in Australia to treat a variety of conditions including pain, mental health diagnoses and sleep. There is currently little research looking into the motivations and experiences of LGBTQA+ people accessing medical cannabis (MC) through healthcare providers. To explore differences in patterns, reasons for using, and experiences of accessing medicinal cannabis between LGBTQA+ people and their cisgender, heterosexual peers. We utilised data collected from an online anonymous cross-sectional survey of individuals (CAMS-22 survey), consisting of adult Australians who had utilised cannabis to treat a medical condition in the previous year. Participants were asked questions about their gender and sexuality, demographic characteristics, patterns and characteristics of MC use, conditions treated, and accessibility to and satisfaction of treatment. Of the 3107 respondents included in these analyses, 2332 (77.3%) self-identified as heterosexual and 686 (22.7%) as sexually diverse. Over 95% of participants identified as cisgender (n = 2932), with only 148 (4.8%) identifying as trans. Sexually diverse participants commenced regular MC use at an earlier age, were more likely to identify a mental health condition and less likely to identify pain as their primary reason for MC consumption, and reported less satisfaction with treatment compared to heterosexuals-primarily around provision of information. Trans participants commenced MC use at an earlier age; were more likely to identify a mental health condition or sleep as their primary reason for MC use; and also reported less satisfaction with treatment than their cisgender counterparts for more interpersonal reasons. LGBTQA+ people use cannabis for medical purposes at significantly earlier ages and primarily to address mental health and substance use concerns. Future research should explore ways in which prescribers can specifically tailor support to meet all physical and mental health needs of LGBTQA+ people, (beyond simply prescribing MC), not only through treatments that they offer, but also through adjunct and complementary services.
The constructed wetland (CW) mimics natural wetland processes, such as filtration, sedimentation, and microbial degradation, to remove contaminants from wastewater, making it a promising method for decentralized greywater treatment and reuse. Yet systematic evaluation of nutrient treatment performance across heterogeneous CWs designed for onsite greywater treatment, remains limited. This study developed an attention-enhanced ensemble model (AEM) integrated with cross-fitted feature importance analysis to investigate the removal of total nitrogen (TN) and total phosphorus (TP) in onsite CWs using a dataset across 18 cities globally. The AEM improved prediction stability and uncertainty by assigning sample-specific weights to complementary base models, including the explainable boosting machine, random forest and extreme gradient boosting, enabling robust simulation under data scarcity and heterogeneity. Feature importance analysis results showed that effluent NH₄⁺-N and influent TN dominated the effluent TN prediction; while influent TP, plant species, and substrate composition governed effluent TP prediction, reflecting their distinct nutrient removal mechanisms. Moreover, the feature analysis identified an optimal HRT of 10-15 h for improved TN control, and a substrate height of 250-300 mm with >40% porosity for efficient TP removal in CW configurations for greywater nutrient removal, providing actionable operational and design guidance for practical application. The results further revealed that environmental heterogeneity and insufficient process-relevant feature representation constrain mechanistic interpretation and model transferability, highlighting the need for temporally resolved and process-oriented monitoring to support future process-informed hybrid modeling frameworks.
We examined whether baseline dentition status was associated with transitions to activities of daily living (ADL) disability, dementia, both ADL disability and dementia, and death in older Chinese adults, and whether denture use further distinguished risk within low-dentition groups. We analysed Chinese Longitudinal Healthy Longevity Survey data from 2008 to 2018. Participants were aged 65 years or older, had baseline natural tooth count data, and had no observed ADL disability or reported dementia at baseline. Dentition status was classified as at least 20 teeth, 1-19 teeth, and 0 teeth. Transition-specific discrete-time complementary log-log models were fitted within a cumulative five-state framework comprising Healthy, ADL disability only, dementia only, both ADL disability and dementia, and death. A total of 10,186 participants contributed 18,688 interval-level observations. The most frequent transitions were to death (n = 5,063) and ADL disability only (n = 2,048). Compared with participants with at least 20 teeth, those with 0 teeth had higher hazards of ADL disability only (HR: 1.20, 95% CI, 1.04-1.39) and death (HR: 1.18, 95% CI, 1.06-1.31). In joint analyses, those with 0 teeth and dentures had the highest hazard of ADL disability only (HR: 1.30, 95% CI, 1.10-1.53), whereas those with 0 teeth and no dentures had the highest hazard of death (HR: 1.33, 95% CI, 1.18-1.49). Dementia-related transitions were sparse. Among older Chinese adults without observed ADL disability or reported dementia at baseline, edentulism was associated with less favourable later-life transitions, most consistently to ADL disability and death. Baseline dentition status may serve as a simple marker of oral functional reserve and broader later-life vulnerability. Baseline dentition and denture status may help identify older adults who warrant broader assessment of function, nutrition, frailty, and oral rehabilitation needs.
Antibody-antisense oligonucleotide (Ab-ASO) conjugates are an innovative class of therapeutics that merge the gene-modulation capabilities of ASOs with the tissue-targeting properties of monoclonal antibodies. Sensitive, selective, and reliable methods to quantify Ab-ASO conjugates in biological samples are critical to understand their pharmacokinetics, pharmacodynamics, toxicity, and biodistribution properties. While ligand-binding assay (LBA) approach is common, it is often limited by the need for multiple custom reagents and narrower dynamic range. In this work, we present a robust hybridization LC-MS/MS strategy for the quantitation of Ab-ASO conjugates using sequence-specific hybridization extraction. Discovery proteomics was utilized to identify and select high-specificity surrogate peptides for the antibody moiety. The method leverages a biotinylated complementary DNA probe to selectively enrich the conjugate through Watson-Crick base pairing, followed by tryptic digestion and LC-MS/MS quantitation of surrogate peptides. The assay was successfully qualified in mouse serum over the range of 10.0 - 10,000 ng/mL and applied to a single-dose pharmacokinetic study, demonstrating high analytical agreement with a benchmark LBA strategy. The LC-MS/MS approach provides a superior dynamic range, simplifies reagent requirements and offers an LC-MS based quantitation platform that was previously unavailable for Ab-ASO conjugate quantitation.
Nutrition education remains insufficient in many health professional training programs despite the central role of diet in the prevention and management of chronic disease. Contemporary nutrition science increasingly recognizes that dietary behaviors and health outcomes are shaped by complex interactions among biological, behavioral, environmental, and food system factors. This perspective proposes an interdisciplinary framework for nutrition education that integrates the complementary expertise of physicians, dietitians, chefs, and farmers. By bridging clinical care, nutrition science, culinary practice, and agricultural systems, such an approach may strengthen the translation of evidence into practice, improve nutrition-related competencies among health professionals, and ultimately enhance population health outcomes.
In this work, an enhanced metaheuristic optimization algorithm, termed the Adaptive LightTrack Top-guided Cuckoo Catfish Optimizer (ALTCCO), is proposed to improve the performance of the original Cuckoo Catfish Optimizer (CCO) in solving complex numerical and real-world optimization problems. ALTCCO integrates three complementary strategies to reinforce population diversity, adaptive search, and convergence stability: (1) a bidirectional cross-interaction mechanism combining horizontal (dimension-wise) and vertical (segment-wise) crossover to enrich information exchange; (2) a LightTrack strategy incorporating historical position memory and stagnation-driven repulsive jumps to escape local optima; and (3) a top-guided adaptive mutation where mutation intensity is dynamically adjusted based on rank-based fitness to balance exploration and exploitation. ALTCCO was rigorously evaluated on 29 CEC2017 benchmark functions, five classic engineering design problems, and a high-dimensional 3D UAV path planning task in a complex constrained environment. Experimental results demonstrate that ALTCCO achieves superior convergence speed, optimization accuracy, and robustness across all test cases. On the CEC2017 benchmark suite, ALTCCO obtained the best results on 28 out of 29 benchmark functions and achieved the lowest average Friedman rank of 1.07 among thirteen competing algorithms. Additional high-dimensional experiments further confirmed its scalability, where ALTCCO maintained the best overall average ranks of 1.21 and 1.34 on the 50-dimensional and 100-dimensional CEC2017 benchmark sets, respectively. In the high-dimensional UAV path planning task, ALTCCO achieved the lowest mean path cost of 141.6121 with a standard deviation of only 2.2920, demonstrating excellent solution quality and stability. Statistical analyses based on the Friedman ranking and Wilcoxon signed-rank test further confirm the significant performance superiority of ALTCCO, establishing it as an efficient and versatile optimization framework for complex engineering applications.
To test whether renal dysfunction modifies the prognostic value of 24-hour lactate clearance for survival to discharge after extracorporeal cardiopulmonary resuscitation (ECPR). Retrospective cohort study with a 24-hour landmark approach. Single tertiary academic medical center. Of 158 patients screened for ECPR, 99 with calculable lactate clearance and available 24-hour creatinine comprised the analytic cohort. None (observational study). Effect modification was tested using multivariable logistic regression with an interaction term (lactate clearance × elevated 24-hour creatinine >2.0 mg/dL), adjusting for age, cardiopulmonary resuscitation duration, shockable rhythm, and baseline lactate. After baseline lactate adjustment, the interaction odds ratio (OR) was 0.63 per 10% increase in clearance (95% confidence interval, 0.45-0.87; p = 0.005), indicating attenuated prognostic value in patients with elevated creatinine. Stratified analyses confirmed that higher clearance was associated with survival only in patients with normal creatinine (OR, 1.30; area under the receiver operating characteristic curve [AUROC], 0.654), whereas no meaningful association was observed with elevated creatinine (OR, 0.98; AUROC, 0.516). The interaction remained robust after excluding patients with chronic kidney disease (OR, 0.59, p = 0.005) and when modeling creatinine continuously (OR, 0.91, p = 0.028). Among patients undergoing ECPR who survive to 24 hours, elevated creatinine defines an interpretation boundary for percentage-based lactate clearance. Clinicians should interpret this metric cautiously when renal dysfunction is present and consider absolute lactate values as complementary information. These findings should be considered hypothesis-generating, given the single-center retrospective design, modest events-per-variable ratio, and the inability to fully disentangle renal-mediated metabolic factors from baseline lactate distribution differences; prospective multicenter validation is required before clinical implementation.
Current physical activity (PA) guidelines recommend reducing prolonged sitting in addition to increasing PA. In this regard, the complementary effects of standing breaks to interrupt sitting, in addition to exercise, have not yet been evaluated. This study tested whether exercise alone or exercise combined with standing breaks enhances cardiometabolic outcomes compared with prolonged sitting in sedentary adults with dyslipidaemia. In this randomized cross-over trial, sixteen adults (mean ± SD: age = 47.8 ± 9.3 years; BMI = 24.6 ± 2.7 kg/m2; 8 women) completed three two-day conditions: prolonged sitting (SIT), prolonged sitting + exercise (FIT), and sitting interrupted with standing breaks (30 min/h) + exercise (MIX). The protocol was conducted in free-living, desk-based work environments, with a single 60-min moderate-intensity cycle ergometer bout performed on the second day. PA and sedentary behavior (SB) were objectively measured and standardized test meals were provided during the laboratory-based metabolic testing day. Postprandial metabolism (primary outcome) including glucose, insulin and triglycerides, was measured over 6 h. Linear mixed effects models with correction for baseline values were used to evaluate condition effects. Postprandial triglyceride (p = 0.112) and glucose (p = 0.150) concentrations did not differ across conditions whereas postprandial insulin responses were significantly lower in MIX than SIT (p = 0.041) and FIT (p = 0.010). Standing breaks combined with exercise did not reduce postprandial triglyceride or glucose concentrations, but improved insulin responses more than exercise alone in sedentary adults with dyslipidaemia. These findings suggest that interrupting prolonged sitting may provide additional metabolic benefits alongside structured exercise in at-risk populations. Trial Registration: https://clinicaltrials.gov/study/NCT06277713 (Registered February 12, 2024).
Chimeric RNAs, formed by the fusion of exons from two or more distinct genes, represent a significant class of noncanonical transcripts with increasing implications in cancer biology, development, and other biological processes. Their inherent novelty and the potential for sequence similarity with parental transcripts pose significant challenges for accurate detection and validation. While next-generation sequencing (NGS) has become the primary tool for chimeric RNA discovery, orthogonal validation methods are crucial to confirm their existence, delineate their precise structure, and quantify their abundance. Mass spectrometry (MS)-based approaches offer a powerful and complementary strategy for the robust validation of chimeric RNAs. This chapter will delve into the principles and applications of MS-based techniques for the definitive characterization of these fusion transcripts, highlighting their strengths in providing direct evidence of the chimeric junction at the peptide level, confirming the reading frame, and offering quantitative insights. We will explore various MS workflows, including targeted and untargeted peptidomics, and discuss the critical considerations for sample preparation, data acquisition, and bioinformatic analysis to ensure reliable and high-confidence validation of chimeric RNAs.