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PubMed2026

Development and Crossover Evaluation of an Artificial Intelligence-Assisted System for Solid Pancreatic Lesion Detection and Pancreatic Parenchyma Recognition in Endoscopic Ultrasonography (With Video).

BACKGROUND AND STUDY AIMS: Pancreatobiliary endoscopic ultrasonography (EUS) is technically demanding, and supervised training opportunities are limited. We developed an artificial intelligence (AI) overlay system for detecting solid pancreatic lesions (SPL) and recognizing pancreatic parenchyma (PP) and evaluated its effect on reader performance. PATIENTS AND METHODS: Across six centers, two deep learning-based models were trained using expert-annotated EUS frames. We then conducted a randomized, two-sequence, two-period crossover reader study in which eight endosonographers (five novices and three experts) interpreted image sets with and without AI assistance. The primary endpoint was superiority of sensitivity for SPL detection among novices; key secondary endpoints included specificity and PP recognition. RESULTS: From 118 patients, 120 SPL-positive/negative image sets and 160 PP-positive/negative image sets were constructed. Among novices, AI assistance improved SPL detection sensitivity (88.7% vs. 76.8%, p < 0.001) and accuracy (86.4% vs. 78.7%), while specificity met the predefined noninferiority criterion (84.2% vs. 80.5%, p < 0.001). For PP recognition, sensitivity increased numerically (86.3% vs. 83.3%) but did not meet the predefined superiority criterion (p = 0.095); specificity met the noninferiority criterion (87.8% vs. 81.0%), and accuracy increased from 82.1% to 87.0%. Among experts, sensitivity was maintained for both tasks, whereas specificity increased with AI assistance. CONCLUSIONS: AI assistance improved SPL detection among novice endosonographers. For PP recognition, sensitivity increased without reaching statistical superiority, whereas specificity met the predefined noninferiority criterion. These findings support a potential adjunctive role for AI in EUS interpretation.

Humans↗

PubMed2026

Reducing state anxiety with alpha-frequency transcranial alternating current stimulation.

BACKGROUND: Anxiety reactivity to acute stress is a transdiagnostic vulnerability factor. We tested whether a single session of alpha-frequency transcranial alternating current stimulation (tACS) targeting the frontoparietal control network reduces stress-evoked state anxiety in healthy adults. METHODS: In a randomized, blinded, sham-controlled study, 42 participants (mean age 58.9 years) completed an acute stress task before and after stimulation. The task was an adapted moving-circles paradigm in which circle collisions triggered a brief aversive event (mild electric shock plus unpleasant noise and a white flash). Active stimulation consisted of 20 min of 10-Hz tACS (2.0 mA/channel; 30-s ramp up/down) delivered via electrodes at F3, P3, Cz, and T7 (0° phase at F3/P3; 180° at Cz/T7). Sham stimulation used the same montage and ramp periods but no sustained current. RESULTS: State anxiety showed a significant Time × Protocol interaction (F(1,35) = 4.22, p = .047): STAI-S decreased after active tACS (Δ = -3.16) but increased slightly after sham (Δ = +1.17). Perceived stress appraisal (SAAS) did not change. Resting-state alpha power at F3/P3 showed no reliable pre-post effects. During the task, left-frontal relative alpha differed by protocol and showed a trend toward larger increases following active tACS. Electrodermal and pupil indices changed across sessions in both groups, with no differential stimulation effects. CONCLUSIONS: A single alpha-tACS session produced a modest, selective reduction in stress-evoked state anxiety, supporting oscillatory neuromodulation as a scalable approach to dampen anxiety reactivity.

Humans↗

PubMed2026

Machine learning-assisted Mn-N-C nanozyme colorimetric sensor array for trace-level detection of biogenic amines in meat.

Accurate detection of biogenic amines (BAs) in meat remains challenging due to their high structural similarity and co-occurrence. Herein, an Mn-N-C nanozyme was synthesized via a metal-organic framework confined pyrolysis strategy, possessing excellent oxidase (OXD)- and peroxidase (POD)-like activities. The dual enzyme-like activity showed Km values of 0.1584 mM (OXD) and 0.1498 mM (POD), respectively, in detection system. Leveraging these properties, a colorimetric sensor array was constructed, enabling the detection of four representative BAs within a concentration range of 2-10 ppm with 100% classification accuracy. In addition, a concentration independent recognition model based on an artificial neural network was developed to address signal nonlinearity interference in meat. The integrated system achieved accurate trace-level identification of BAs in perishable fish, pork, and chicken, demonstrating its applicability for early-stage BAs monitoring and quality deterioration warning during storage and transportation.

Biogenic Amines↗

PubMed2026

Microplastic contamination in South Asian commercially important seafood: A comprehensive assessment of occurrence, source, and human health risk.

Seafood is a cornerstone of global food security and human nutrition, serving as the primary source of animal protein for more than one-fourth of the global population, with South Asia representing one of the world's fastest-growing seafood-consuming regions. However, escalating microplastic (MP) pollution in marine ecosystems poses an emerging threat to seafood safety and human health, yet a comprehensive regional assessment of MP contamination in South Asian seafood remains lacking. This study presents the first region-wide systematic synthesis of the literature on MP contamination in commercially important seafood across South Asia, integrating occurrence patterns, human exposure assessment, polymer-specific hazard evaluation, and bibliometric analysis to address this critical knowledge gap. The meta-analysis estimated an average microplastic exposure of 145 particles/person/day through seafood consumption in South Asia, with fish contributing the highest intake (121 particles/person/day). The detected polymers were classified into PHI hazard levels I-IV, with polyvinyl chloride (PVC), polyurethane (PU), and polyacrylamide (PAM) representing the highest hazard categories. The mean pollution load index (PLI) was 7.71 (Category I), with crustaceans exhibiting the highest contamination (PLI = 10.07). Polypropylene was the predominant polymer, whereas fragments and blue particles were the most frequently reported microplastic characteristics. These findings provide the first regional baseline for assessing microplastic contamination, polymer-associated hazards, and human exposure through seafood consumption in South Asia, underscoring the need for standardized monitoring and targeted mitigation strategies to safeguard seafood safety and public health.

Animals↗

PubMed2026

Functions of tandem-repeat galectins and domain coordination governs galectin-4 activity in grass carp (Ctenopharyngodon idella).

Galectins are β-galactoside-binding lectins that play essential roles in innate immunity. Among them, tandem-repeat galectins (TrGals), typically composed of two distinct carbohydrate-recognition domains (CRDs) connected by a linker peptide, are well established as key regulators of pathogen recognition and host defense in mammals. However, their structural diversity and immunological functions in teleost fish remain poorly understood. In this study, five TrGals (Gal-4, Gal-8a, Gal-8b, Gal-9, and Gal-9like) were identified in grass carp. Sequence and structural analysis revealed that Gal-8a/b, Gal-9, and Gal-9like possess the canonical two-CRD architecture, whereas Gal-4 uniquely contains four highly similar tandem-repeat domains. All five TrGals were broadly expressed across examined tissues, with predominant expression in the liver. Upon Aeromonas hydrophila infection, Gal-4, Gal-8a, Gal-8b, and Gal-9 were rapidly up-regulated at early time points (3-6 h). To elucidate the functional significance of CRD number, recombinant full-length CiGal-4 (CiGal4-full) and three truncated variants containing one, two, or three CRDs (CiGal4-1CRD, CiGal4-2CRD, and CiGal4-3CRD) were generated and systematically characterized. All recombinant proteins contained the conserved β-sheet structure typical of galectin CRDs. Functional assays revealed that CiGal4-full displayed the strongest growth-inhibitory activity against all tested bacteria, whereas CiGal4-1CRD showed the weakest effect. Notably, CiGal4-2CRD exhibited the most potent bactericidal activity, surpassing the full-length protein, while CiGal4-3CRD showed no further enhancement. CiGal4-full and CiGal4-2CRD showed superior carbohydrate-binding activities compared with the other variants. Collectively, these results reveal that CRD copy number alone does not linearly determine galectin function. Instead, domain organization and conformational coordination are critical for optimizing antimicrobial activity. This study provides new insights into the structure-function relationships and evolutionary diversification of galectins in teleosts and highlights their potential as novel antimicrobial and immunomodulatory agents in aquaculture.

Animals↗

PubMed2026

From host response to genomic targets: electrochemical biosensing of tuberculosis biomarkers.

Tuberculosis (TB) remains one of the leading causes of death from a single infectious agent worldwide, with timely diagnosis continuing to be a major challenge, particularly in resource-limited settings. Conventional TB diagnostic methods are limited by low sensitivity, long turnaround times, and an inability to reliably differentiate latent from active disease. Biomarker-based diagnostic strategies have therefore gained increasing attention as they offer the potential to improve early detection, disease differentiation, and treatment monitoring. Herein, we examine electrochemical biosensing strategies for TB diagnostics using a biomarker-class-driven framework, covering host-response biomarkers (IFN-γ and TNF-α), pathogen-derived antigens (ESAT6, CFP10, CFP10-ESAT6, MPT64, Ag85, HspX and LpqH), cell-wall signatures and whole-cell markers (LAM and whole cell Mtb), and genomic markers (Mtb DNA and IS6110). Through structured comparison of recognition elements, biointerface designs, signal amplification strategies, electrochemical techniques, matrices, and validation levels, this review identifies the most promising technical approaches for different TB biomarker classes. It further highlights key translational bottlenecks, including limited clinical validation, buffer-based testing, complex multistep amplification, redox-probe dependence, matrix fouling, and insufficient evidence of manufacturability. This review therefore provides practical guidance for developing electrochemical TB biosensors that are analytically sensitive, clinically relevant, and suitable for decentralized diagnostic applications.

Biosensing Techniques↗

PubMed2026

Oxidative potential of fresh vs. O₃-aged PM2.5 across urban and rural sources in China.

Fine particulate matter (PM2.5) is a major health risk, yet its impacts are still largely assessed using mass concentration, which does not capture toxicity. Recently, oxidative potential (OP) has emerged as a more relevant metric, reflecting the ability of particles to generate reactive oxygen species. A current challenge, especially in China, is understanding how emission sources and ozone (O3) aging affect PM2.5 toxicity, given that O3 is an increasingly important pollutant there. A work by Ma and co-workers published in J. Environ. Sci. (doi.org/10.1016/j.jes.2024.04.023) addressed this by evaluating the OP of fresh and O3-aged PM2.5 from multiple sources in China using the dithiothreitol (DTT) assay. Biomass burning particles exhibited the highest OP, up to 35 times greater than suburban PM2.5, driven by water-soluble organics and transition metals. While O3 aging generally reduced OP, it also induced complex chemical transformations. These findings highlight that PM2.5 toxicity is dynamic and source-dependent, underscoring the need to move beyond mass-based air quality metrics.

Particulate Matter↗

PubMed2026

Policy pathways and historical insights: Canada's evolving approach to psychedelic access for end-of-life distress.

Canada's evolving attitudes toward psychedelic interventions in palliative and end-of-life care reflect a departure from historically prohibitionist policies and an emerging recognition of their therapeutic potential for individuals facing end-of-life distress. This shift parallels international regulatory developments in jurisdictions such as the United States, Australia and parts of Europe, where cautious policy liberalization has signaled growing acceptance of psychedelics within clinical contexts. Canada is also a relevant case because of its formative role in the development of modern palliative care, its contemporary frameworks emphasizing holistic approaches to suffering at the end of life, and its experience with medical assistance in dying, all of which have shaped national conversations about suffering, autonomy, and end-of-life care. Additionally, Canada's distinctive historical approach to drug regulation-marked by federal flexibility, mechanisms for compassionate access, and responsiveness to patient advocacy-combined with rising public demand and incremental provincial changes, may uniquely position the country along a transitional pathway toward clinical integration of psychedelics in palliative care. At the same time, Canadian drug policy remains heterogeneous across substances and provinces, underscoring the political contingency of reform. Within this dynamic landscape, Canada's psychedelic drug policy trajectory aligns with broader international trends toward cautious medicalization and regulated access to psychedelic therapies, while also offering an instructive case for how end-of-life frameworks and federal-provincial governance shape policy development.

Humans↗

PubMed2026

Inhibitory mechanism of phloretin on the AgrA LytTR domain-agr operon complex formation and its application in beef.

Staphylococcus aureus (S. aureus) represents a major foodborne pathogen whose enterotoxin production poses significant challenges to food safety due to its high environmental resistance and limited efficacy of conventional sterilization. Since the expression of enterotoxins is predominantly governed by the agr quorum sensing system, targeting this regulatory pathway has become a strategic choice for virulence control. This study elucidated the mechanism by which phloretin, a potential quorum sensing inhibitor, interferes with the agr system to attenuate virulence. To achieve this, the recombinant AgrA LytTR domain was expressed and purified, and its interaction with phloretin was characterized using thermal shift assays (TSA), electrophoretic mobility shift assays (EMSA), and molecular dynamics (MD) simulations. The results showed that phloretin specifically binds to the AgrA LytTR domain, enhancing its thermal stability and disrupting AgrA LytTR-agr operon binding by reducing the free energy of interaction between them, without causing significant structural rearrangement. Mechanistic analysis indicated that phloretin sterically hinders key β-sheet turn residues (HIS169, ASN201, ARG233), thereby impairing DNA recognition, downregulating RNAIII transcription, and inhibiting agr signaling. In cooked beef, phloretin significantly inhibited the secretion of enterotoxins and α-hemolysin, while delaying lipid oxidation and protein degradation, and maintaining the meat texture. These findings suggested that phloretin is a multifunctional substance with anti-virulence, antioxidant, and preservative properties, demonstrating its potential as a natural food preservative.

Phloretin↗

PubMed2026

Selective monitoring of trace-level catechin and myricetin in herbal and aqueous matrices using magnetic MIP-DSPME: Optimization via design of experiments.

A novel dispersive solid-phase microextraction approach utilizing a magnetic molecularly imprinted polymer (MMIP) integrated with HPLC-UV detection was developed for the concurrent quantification of catechin and myricetin in herbal extracts and aqueous samples. The sorbent was engineered as a core-shell nanocomposite, consisting of a selective polymer layer deposited onto Fe3O4@SiO2-APTMS magnetic nanoparticles. Dual-template imprinting using catechin and myricetin generated complementary binding cavities within the polymer framework. Experimental variables influencing extraction were systematically screened and subsequently optimized. A Plackett-Burman design was first applied to identify the most influential factors, with pH and sorption time identified as the dominant variables. These parameters were subsequently fine-tuned using a central composite design, and the optimization process was completed in only 30 experimental runs. The sorption characteristics of the imprinted sorbent (MMIP) were compared with those of its non-imprinted counterpart (MNIP). The MMIP demonstrated markedly higher maximum binding capacities (Qmax), reaching 119.3 mg g-1 for myricetin and 112.1 mg g-1 for catechin, whereas the corresponding values for the MNIP were 32.55 and 32.08 mg g-1, respectively. Moreover, the affinity constants (KL = 0.760-0.950 L mg-1) were approximately 2.3-fold higher for the MMIP, confirming its stronger and more selective interactions with the target analytes. The selectivity coefficients for the targeted flavonoids relative to structurally related compounds, including ferulic acid, p-coumaric acid, melatonin, and curcumin, exceeded 3.5 for the MMIP, whereas the corresponding values for the MNIP were close to 1.1, demonstrating the high molecular recognition capability of the imprinted sorbent. Method validation demonstrated limits of detection (LODs) of 0.33-0.59 ng mL-1 and limits of quantification (LOQs) of 1.10-1.96 ng mL-1, and excellent linearity over the concentration range of 5.0-5500 ng mL-1 (R2 > 0.998). The method achieved recoveries of 93.96% to 105.69% with RSDs below 5.5%, while the preconcentration factors ranged from 209 to 229. Furthermore, the sorbent retained more than 95% of its extraction efficiency after four consecutive reuse cycles and more than 80% after six cycles, demonstrating excellent stability and reusability. The proposed method was successfully applied to the analysis of six medicinal plant extracts and water samples, showing negligible matrix interference and superior sensitivity, selectivity, and operational simplicity compared with conventional solid-phase extraction methods.

Flavonoids↗

PubMed2026

A host-encoded prophage targets a Candidate Phyla Radiation bacterium and shapes episymbiotic interactions.

The Patescibacteriota, also known as the Candidate Phyla Radiation (CPR), represent a large lineage of ultrasmall bacteria with highly reduced genomes and obligate dependence on bacterial hosts. Although genomic analyses have revealed CRISPR-Cas and restriction-modification systems in many CPR genomes, no cognate bacteriophages (phages) have been isolated, leaving CPR-phage interactions unexplored. Nanosynbacter lyticus TM7x, the first cultivated CPR bacterium, grows episymbiotically on its host, Schaalia odontolytica XH001, in the human oral microbiome. Here, we identify Xhp1, an inducible prophage of XH001 that is preferentially activated during episymbiosis with TM7x. Released Xhp1 particles infect prophage-free XH001 via distinct strategies determined by host growth mode, establishing lysogeny under planktonic conditions but driving lytic infection during surface-associated growth. Xhp1 also binds efficiently to TM7x and exhibits limited infection under the conditions tested, indicating direct phage-CPR interactions. Importantly, TM7x modulates Xhp1 availability in a spatially dependent manner. In planktonic culture, free-floating TM7x reduces lysogenic conversion of XH001ΔXhp1, consistent with TM7x acting as a phage sink that lowers effective phage concentration. In contrast, during surface-associated growth, TM7x increases XH001ΔXhp1 susceptibility to lytic infection, likely by locally concentrating phage particles within a constrained niche. These results demonstrate that CPR bacteria can regulate viral encounter rates through spatial organization. In spatially structured environments such as oral biofilms, such modulation may shape infection dynamics and community structure. Together, this work characterizes the first CPR-targeting phage and reveals a an important role for phages in CPR-host bacteria interactions.

Prophages↗

PubMed2026

Towards microplastic bioremediation: Fungal degradation of pristine and pretreated high-density polyethylene and polystyrene.

Microplastic (MP) contamination has become a significant ecological issue because of its enduring existence in the ecosystem and its possible negative impacts. Therefore, using degrading strategies to eliminate these stubborn polymers has been a subject of scientific research. However, the currently used degradation methods are relatively inefficient. Given the pervasiveness of High-Density Polyethylene (HDPE) and Polystyrene (PS) and their resistance to biodegradability, disposal strategies are critical and must be addressed. This manuscript examines the biodegradation of pristine and UV-treated HDPE and PS MPs by Aspergillus flavus species in minimal growth media over 70 days. The maximum weight loss observed at 70 days for pristine HDPE and PS in sole carbon source (SCS) media was (29.33 ± 0.28) % and (17.67 ± 0.35) %, respectively. Whereas, for UV-treated HDPE and PS MPs, the % weight reduction was (33 ± 0.21) % and (25 ± 0.19) %, respectively. UV-treated MPs exhibited greater weight reduction, as UV induced oxygenated functional groups enhance polymer susceptibility to enzymes, thereby promoting biodegradation. HDPE MPs typically show a higher proportion of particles in the lower size range compared to PS MPs. This assertion was based on the weight loss, particle size distribution, and SEM analysis. Furthermore, chemical changes were evaluated using Fourier transform Infrared Spectroscopy (FTIR) analysis, which also displayed chemical oxidation occurring during biodegradation. Liquid Chromatography-Mass Spectrometry (LC-MS) results indicate that UV pretreatment enhances biodegradability by promoting chain scission. These findings further suggest that this fungus's natural and ubiquitous occurrence in terrestrial and marine environments may actively contribute to MP biodegradation while requiring few nutrients.

Microplastics↗

PubMed2026

Optimization of a niosomal formulation for Quercetin delivery: Comparative effects on growth performance, antioxidant and immune responses, and disease resistance against Streptococcus iniae in rainbow trout (Oncorhynchus mykiss).

Quercetin (QUR) is a flavonoid with antibacterial and antioxidant properties that has been studied for its effects on fish health and the immune system. Due to the low bioavailability of QUR, the present study was primarily aimed at developing a niosomal formulation of QUR to enhance its bioavailability and therapeutic properties. The performance of niosomal QUR was then compared with that of its free form by evaluating their effects on the growth and immune system of rainbow trout, Oncorhynchus mykiss. For this purpose, an optimal QUR-containing niosome was formulated by testing different proportions of cholesterol, surfactant, and stabilizer, and the niosomes were then added to the fish diet. A QUR-free diet and a diet containing QUR-free niosomes (QFN) were considered control groups. Niosomes prepared at low hydrophilic-lipophilic balance (HLB) values showed higher QUR entrapment efficiency (QUR-EE%) (P < 0.01). An increase in the molar ratio of cholesterol to surfactant significantly reduced QUR-EE% (P < 0.05). A surfactant/cholesterol/stabilizer ratio of 1:1:0.1 increased QUR-EE% (P < 0.05). The particle size of the niosomes was also affected by HLB and the surfactant/cholesterol/stabilizer ratio. Low HLB values resulted in smaller particle sizes (P < 0.01). Furthermore, a surfactant/cholesterol/stabilizer ratio of 1:1:0.1 resulted in the smallest niosomal particle size (P < 0.05). The presence of diacetyl phosphate as the stabilizer in the formulation improved the niosomal zeta potential to -40.55 mV. The optimal niosomal formulation (HLB = 6.6; surfactant/cholesterol/stabilizer ratio of 1:1:0.1) remained stable at 2 °C over 10 days of storage, as the niosomal QUR content and size did not show significant changes during this period (P > 0.01). After preparation of the diets containing the optimal niosomal QUR, fish were fed the experimental diets for two months. QUR, in both niosomal and free forms, resulted in better growth performance than the QUR-free diets (P < 0.01). There were no significant differences in growth performance between the free and niosomal forms of QUR; however, 500 mg/kg QUR showed significantly better growth performance than 250 mg/kg QUR (P < 0.01). Although both the niosomal and free forms of QUR enhanced immune and antioxidant components in the fish, the effects of the niosomal form were more significant (P < 0.01). In addition, QUR in both free and niosomal forms reduced fish mortality after challenge with Streptococcus iniae. In conclusion, the results of this study suggest that the niosomal form of QUR has strong potential for improving the immune system of fish and increasing resistance to S. iniae infection.

Animals↗

PubMed2025

Tracking microplastic contamination across seasons in a freshwater reservoir: Evidence from surface water, sediments, and fishes.

Microplastics (MPs) are prevalent contaminants in aquatic environments, posing substantial ecological and health risks. These particles migrate within the different layers of aquatic bodies with time and affect the respective biota. Thus, to get an in-depth understanding of the particles, this current study investigated the seasonal distribution, morphological and chemical characteristics, along with potential ecological and human health impacts in the samples including surface water, sediment, and fish from a drinking water supplying reservoir in eastern India. Across three different seasons, pre-monsoon, monsoon, and post-monsoon samples were collected using optimized methods. Results revealed distinct seasonal trends: MP abundance in surface water peaked during the monsoon (mean: 1.15 MPs/L), while sediment showed the highest concentrations in the pre-monsoon (mean: 596 MPs/kg), indicating temporal accumulation dynamics influenced by runoff, hydrodynamics, and sedimentation. Fish gut analysis confirmed ingestion of MPs across five species, with concentrations ranging from 26 to 100 MPs/kg, depending on feeding habits. The most dominant MP type were fragments, followed by fibers, films, and beads. Polymer analysis via µFTIR identified polyethylene, polypropylene, and polyvinyl chloride as prevalent, with hazard assessments (i.e., Polymer Hazard Index (PHI)) indicating medium to very high ecological risks. Heavy metal association was more dominant in the MPs isolated from sediments than the waterborne MPs. Pollution Load Index (PLI) values were > 1 in most seasons, confirming contamination. Health risk analysis suggested potential exposure through both drinking water and fish consumption. This study emphasizes the need for seasonal monitoring, improved waste management, and mitigation strategies to address MP pollution in freshwater ecosystems.

Microplastics↗

PubMed2026

"Orphaned bereavement": Toward a public health model for bereavement.

Bereavement is increasingly recognized as a public health concern, yet support systems in many welfare states continue to allocate support according to the circumstances of death rather than the functional needs of bereaved families. Existing bereavement frameworks have substantially advanced understanding of social recognition and public legitimacy but provide more limited guidance for understanding how institutional responsibility for bereaved families is organized. using Israel as a bereavement-saturated case, this study introduces the concept of orphaned bereavement to describe bereavement in which no institution holds clearly defined and continuing responsibility for identifying needs, coordinating support, and ensuring continuity of care. Drawing on 25 semi-structured interviews with five bereaved family members and 20 professionals, analyzed using reflexive thematic analysis, the analysis generated three interrelated themes: institutionalized invisibility and unequal recognition; reorganizing life in the absence of institutional support; and pathways toward a needs-based model of bereavement support. The findings extend existing theories of disenfranchized grief and grievability by introducing institutional responsibility as a complementary lens for understanding bereavement inequality and support a needs-based public health approach in which support is organized according to families' evolving functional needs rather than the circumstances of death.

Journal Article↗

PubMed2026

Access to palliative care in rural settings: A mixed-methods systematic review.

BACKGROUND: Rural populations experience persistent inequities in access to palliative care. Existing evidence often describes individual barriers separately, with less attention to how access breaks down across the care pathway or how different service configurations shape access. OBJECTIVES: To synthesise evidence on access to palliative care in rural settings and examine how access barriers, service models, and implementation conditions interact across the care pathway. METHODS: A mixed-methods systematic review using a convergent integrated approach searched nine databases (PubMed, Embase, CINAHL, Web of Science, Scopus, PsycINFO, CNKI, WanFang, SinoMed) from inception to 15 March 2026, supplemented by hand-searching. Eligible studies were primary qualitative, quantitative, and mixed-methods studies on access to palliative care for adults in rural or non-urban settings. Two reviewers independently screened studies, extracted data, and assessed quality using the Mixed Methods Appraisal Tool. Findings were mapped to the Levesque access framework, analysed using the updated Consolidated Framework for Implementation Research, and integrated through mixed-methods synthesis, with additional coding of service models. RESULTS: Thirty-four studies were included, of which 26 were conducted in high-income countries and eight in low- and middle-income countries. Service configurations included specialist or hospice-oriented care, generalist or primary-care-oriented care, mixed specialist-generalist models, home-based and caregiver-centred care, nurse-coordinated services, telehealth-supported care, and community or implementation-oriented approaches. Access broke down cumulatively across four interdependent stages: recognition, entry, reach, and use and continuity, with affordability constraining every stage. Recognition was limited by low awareness, poor service visibility, and delayed identification of need. Entry was shaped by stigma, trust, family expectations, and unclear referral processes. Reach was constrained by distance, transport, workforce shortages, limited specialist capacity, and weak infrastructure. Use and continuity were affected by fragmented coordination, weak transitions, unstable follow-up, and reliance on family caregivers. Access problems varied across service configurations. Evidence on service innovations was methodologically less certain, and the overall evidence base remained concentrated in high-income countries. CONCLUSIONS: Access to palliative care in rural settings is best understood as a pathway and service-configuration problem rather than simply a deficit in service availability. Improving access requires earlier recognition, clearer referral routes, stronger specialist-generalist and nursing links, better support for family caregivers, and greater attention to affordability, continuity, and rural settings with limited resources. REGISTRATION: International Prospective Register of Systematic Reviews: CRD420261340783.

Health Services Accessibility↗

PubMed2026

Experiences and perceptions of lay bystanders responding to out-of-hospital cardiac arrest: A qualitative systematic review.

BACKGROUND: To synthesize the experiences and perceptions of lay bystanders before, during, and after responding to out-of-hospital cardiac arrests. METHODS: Seven English and Chinese databases were searched from their inception to July 31, 2026, supplemented with citation tracking. Two reviewers independently selected studies, appraised methodological quality using the Joanna Briggs Institute (JBI) critical appraisal checklist for qualitative research, and extracted the findings and supporting illustrations. Unequivocal and credible findings were synthesized using JBI meta-aggregation, and confidence was assessed using confidence in the evidence from reviews of qualitative research. RESULTS: Eight studies involving 209 participants were included. Thirty-three findings were grouped into 12 categories and 4 were synthesized findings concerning the motivators and inhibitors of response, recognition and appraisal of out-of-hospital cardiac arrest, conditions facilitating or impeding cardiopulmonary resuscitation and automated external defibrillator use, and post-event psychological responses and adjustment. Confidence in the evidence from reviews of qualitative research was moderate for the 1st 3 synthesized findings, and low for the 4th. CONCLUSION: Bystander response is a continuum that extends from event recognition and action to post-event adjustment. Out-of-hospital cardiac arrest systems should provide realistic preparations, clear on-scene support, proportionate information, and psychological support after an event.

Humans↗

PubMed2026

Molecular Determinants and Therapeutic Targeting of Stop Codon Readthrough in Eukaryotic Translation.

Accurate translation termination is essential for proteome integrity and in eukaryotes is primarily governed by the release factors eRF1 and eRF3, which ensure precise recognition of stop codons and efficient release of nascent polypeptides. However, proteome integrity is challenged by mutations that generate premature termination codons (PTCs), leading to truncated, nonfunctional proteins and degradation of the aberrant transcript via nonsense-mediated mRNA decay (NMD). Collectively, these events account for ∼1800 human genetic diseases. Translational readthrough, the process by which near-cognate tRNAs decode stop codons and allow ribosomes to continue elongation beyond the stop codon, represents a possibility to suppress PTCs and restore full-length protein synthesis. Initially discovered in viruses as a mechanism to expand coding capacity, readthrough is now recognized as a regulated feature of eukaryotic gene expression influenced by both cis-acting sequence elements and trans-acting factors. Recent evidence highlights the remarkable context dependence of readthrough, revealing variation across transcripts, tissues, and developmental stages. In this review, we examine the molecular determinants that define stop codon recognition and readthrough efficiency, with particular emphasis on nucleotide context. We further discuss the mechanisms and binding sites of small molecules that promote PTC readthrough, and summarize the clinical development landscape of readthrough-inducing compounds for the treatment of diseases caused by nonsense mutations.

Humans↗