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PubMed2026

Corneal Epithelial Alterations Associated With Cyclin-Dependent Kinase 4/6 Inhibitor Therapy in Hormone Receptor-Positive Breast Cancer.

IMPORTANCE: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are standard therapy for hormone receptor-positive (HR+), HER2-negative breast cancer. By blocking the G1/S cell-cycle transition, these agents may impair renewal of the corneal epithelium. No controlled study has systematically evaluated corneal epithelial changes in patients receiving CDK4/6 inhibitors. OBJECTIVE: To determine whether CDK4/6 inhibitor-based therapy is associated with cornealepithelial alterations independent of aromatase inhibitor exposure and tear film dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Retrospective comparative cross-sectional study at a tertiary ophthalmology center. A total of 132 women were enrolled: 45 receiving a CDK4/6 inhibitor plus an aromatase inhibitor (CDKAI group), 44 receiving aromatase inhibitor monotherapy (AI group), and 43 age-matched postmenopausal controls without systemic oncologic therapy. EXPOSURES: CDK4/6 inhibitor (ribociclib, palbociclib, or abemaciclib) combined with an aromatase inhibitor; aromatase inhibitor alone; or no systemic oncologic therapy. MAIN OUTCOMES AND MEASURES: Prevalence and severity of punctate epitheliopathy and vortex keratopathy, assessed by a masked ophthalmologist. Secondary outcomes included Schirmer I test, tear film break-up time, and Ocular Surface Disease Index (OSDI). RESULTS: PE was present in 44.4% of eyes in the CDKAI group vs 4.7% in the AI group and 2.3% in controls (χ² = 34.31; P < .001). All moderate (13.3%) and severe/complicated (8.9%) PE cases occurred exclusively in the CDKAI group. Vortex keratopathy was observed in 13.3% of CDKAI patients and in none of the other groups (P = .025). Schirmer values, tear film break-up time, and OSDI scores did not differ among groups (all P > .05). Within the CDKAI group, PE was not associated with treatment duration (P = .963) or tear film parameters. CONCLUSIONS AND RELEVANCE: In this comparative study, CDK4/6 inhibitor-based therapy was associated with significantly higher prevalence and severity of PE and vortex keratopathy, independent of aromatase inhibitor exposure and in the absence of measurable tear film dysfunction. These findings suggest a direct cytostatic effect on the corneal epithelium. Symptom scores were low, although OSDI interpretation was limited by incomplete responses. Proactive corneal surface evaluation with fluorescein staining may be warranted during CDK4/6 inhibitor treatment.

Humans↗

PubMed2026

A validated sensitive LC-MS/MS method and its application in elucidating the unique ocular pharmacokinetic profile of 0.01% atropine underpinning its clinical utility for myopia.

A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify atropine in ten rabbit ocular tissues enabling systematic characterization of the ocular pharmacokinetic profile of 0.01% atropine sulfate eye drops after a single topical administration. The method demonstrated excellent linearity (coefficient of determination, R2 ≥ 0.9908) across all matrices, with lower limits of quantification (LLOQ) of 0.05 ng/mL for most tissues and 0.10 ng/mL for retina and lens; intra- and inter-day accuracy, precision, matrix effects, extraction recoveries, and stability all met the acceptance criteria. Following a single bilateral topical dose (50 μL/eye) in New Zealand White rabbits, atropine distributed rapidly into all 12 ocular compartments (the sclera further divided into three anatomical regions) with marked heterogeneity-the highest exposures were found in conjunctiva and cornea, a distinct anterior-to-posterior concentration gradient was observed in the sclera, sustained retention was noted in the retina (mean residence time from zero to the last measurable time point, MRT0-t 3.30 h), while aqueous and vitreous humor eliminated rapidly (elimination half-life, t₁/₂ < 0.7 h), and all tissues except aqueous humor followed a two-compartment model. This validated method and the comprehensive pharmacokinetic data reveal that topically applied 0.01% atropine achieves sustained exposure in key myopia-regulating tissues (retina, choroid, posterior sclera) with low exposure in side-effect target tissues (iris, ciliary body, lens).

Animals↗

PubMed2026

Diversification of yeast proteins as an approach for the development of sustainable food systems.

Despite growing trend in sustainable protein sources, yeast proteins have mainly been explored as a source of bioactive peptides using a monospecies and general protein approach. The contribution of highly abundant protein fractions in the yeast proteome to peptide formation remains insufficiently investigated, limiting a comprehensive understanding of yeast proteins as optimized peptide sources. The current review presents a systematic analysis of yeast proteins as emerging protein sources and evaluates the suitability of high-abundance proteins as bioactive peptide precursors by in silico techniques. Moreover, brewery by-product and single-cell yeast protein approaches are compared in terms of composition and techno-functionality whereas peptide formation mechanisms (in situ and ex situ) and regulatory aspects for food applications are also addressed. Cytoplasmic metabolic proteins, particularly glycolytic enzymes (GAPDH), are identified as highly abundant fractions of the yeast proteome. Proteins associated with cell and organelle membranes also contribute substantially based on cellular localization. These findings imply that such proteins may act as key precursors of yeast-derived bioactive peptides. In silico hydrolysis with Alcalase suggests a tendency toward the generation of short-chain peptides (3-11/14 aa), which may support biological activity. Moreover, peptide profiles appear to vary across yeast species, highlighting the role of species diversity in peptide generation. While single-cell yeast protein allows more controlled production than brewery by-products, nucleic acid content in both may limit applications. Overall, yeast proteins appear to be metabolically adaptable and species-diverse sources for various biological peptides.

Saccharomyces cerevisiae↗

PubMed2026

Comparing the efficacy and safety of unilateral versus bilateral spinal anesthesia: a meta-analysis and systematic review.

BACKGROUND: Unilateral spinal anesthesia has gained increasing attention in recent years. Emerging evidence suggests that it provides comparable analgesia to conventional bilateral spinal anesthesia while reducing adverse effects, and its efficacy and safety compared to bilateral spinal anesthesia remains controversial. OBJECTIVE: This systematic review and meta-analysis aims to evaluate and compare the efficacy and safety of unilateral versus bilateral spinal anesthesia. DESIGN: Systematic reviews and meta-analysis of randomized controlled trials (RCTs). DATA SOURCES: A systematic search was conducted across PubMed, EMBASE, and Cochrane Library from inception to December 10, 2024. ELIGIBILITY CRITERIA: Included studies were randomized controlled trials involving adult patients (≥18 years) undergoing surgery under spinal anesthesia, comparing unilateral versus bilateral spinal anesthesia for efficacy and adverse effects. Studies that focused exclusively on either unilateral or bilateral spinal anesthesia were excluded. The comparator group used the same local anesthetic as the experimental group, with no restrictions on adjuncts (e.g. fentanyl, morphine). RESULTS: Nineteen randomized controlled trials including 1191 patients met the inclusion criteria. Compared with bilateral spinal anesthesia, unilateral spinal anesthesia has a longer onset of sensory blockade (MD = 2.58, 95% CI: 0.93 to 4.22, p = 0.002), a shorter duration of sensory blockade (MD = -27.83, 95% CI: -39.25 to -16.42, p < 0.00001). In addition, unilateral spinal anesthesia significantly reduced the incidence of hypotension (RR = 0.40, 95% CI: 0.31 to 0.52, p < 0.0001), nausea and vomiting (RR = 0.20, 95% CI: 0.07 to 0.56, p = 0.002), and post-dural puncture headache (RR = 0.44, 95% CI: 0.23 to 0.81, p = 0.009). No statistically significant differences were observed in bradycardia and urinary retention. Collectively, these findings support unilateral spinal anesthesia as a strategy that may enhance perioperative safety while maintaining adequate anesthetic efficacy in appropriately selected patients. CONCLUSIONS: Unilateral spinal anesthesia may offer a favorable balance between anesthetic efficacy and safety compared with bilateral spinal anesthesia, although its clinical utility may depend on surgical duration and patient characteristics.

Humans↗

PubMed2026

Phosphorus modulates starch granule development and metabolic partitioning in wheat grain: Insights from SGAP proteomics and nutrition and processing quality.

This study investigates how phosphorus (P) levels are associated with carbon-nitrogen metabolism in wheat grains. Optimal P application (105 kg P₂O₅ ha⁻¹) was associated with enhanced pericarp-endosperm coordination, increased carbon allocation to the endosperm, and early B‑type starch granule formation. Starch granule‑associated protein (SGAP) proteomics showed that optimal P upregulated cytoskeletal and starch‑synthesis proteins bound to starch granules in the endosperm, while reducing storage protein degradation‑related SGAPs in the pericarp. These metabolic adjustments were correlated with increased grain‑filling intensity and duration, and were associated with the highest theoretical grain weight (50.70 mg). Furthermore, optimal P was associated with enrichment of amino acid biosynthesis pathways and with higher levels of essential amino acids (e.g., lysine and threonine by 17.0--26.8%) and an improved essential amino acid profile without altering total protein content. In contrast, excessive P (210 kg P₂O₅ ha⁻¹) was associated with disrupted inter‑tissue coordination but did not simply impair grain filling; instead, HP corresponded to a unique developmental program: it was linked to an early burst of C‑type starch granules (0∼5 µm) at 7 DPA, yet by maturity achieved the highest proportion of large A‑type granules (56.8%) and the highest total starch content (63.5%), together with elevated endosperm phosphorus at 14 DPA and enrichment of spliceosome‑related pathways. HP also showed higher levels of several functional amino acids (glutamate, cysteine, histidine, proline) compared to P0. However, HP was associated with a higher gliadin/globulin ratio and did not improve grain yield. These findings suggest that phosphorus supply is associated with grain quality through tissue‑specific metabolic reprogramming, and that precision management-rather than maximized application-warrants consideration for optimizing both yield and processing quality.

Triticum↗

PubMed2026

Natural products alleviate exercise-induced fatigue by modulating gut microbiota: a systematic review.

BACKGROUND: Exercise-induced fatigue critically impairs athletic performance and training quality. The gut microbiota, as a key regulator of the "gut-muscle axis," has emerged as a promising anti-fatigue target. Natural products - owing to their diverse sources, structural complexity, and favorable safety profiles - have attracted growing research interest. However, a systematic synthesis comparing their anti-fatigue effects via gut microbiota modulation across different sources is lacking. SCOPE AND APPROACH: We systematically searched PubMed, Web of Science, the Cochrane Library, and CNKI for original studies that administered natural products and concurrently assessed gut microbiota changes and anti-fatigue outcomes. Twenty-six studies (25 animal experiments and 1 human trial) were included and categorized into seven groups by source and chemical characteristics. A descriptive systematic review was conducted to identify common mechanisms and source-specific differentiations. KEY FINDINGS AND CONCLUSIONS: The enrichment of short-chain fatty acid (SCFA)-producing bacteria and the activation of the SCFA-AMPK/PGC-1α axis were shared core events across all product categories. However, source-dependent mechanistic divergences emerged: polysaccharides acted primarily as fermentable substrates with an optimal dose window; polyphenols and saponins exerted dual modulation on both microbiota and host signaling pathways; compound extracts achieved systemic synergy through functional complementation; marine- and animal-derived products exhibited unique targeting profiles and rapid action. Intestinal barrier maintenance and brain-gut axis regulation further extended the anti-fatigue repertoire. Collectively, natural products possess a solid mechanistic basis for alleviating exercise-induced fatigue via gut microbiota remodeling. The differentiated characteristics of these methods in targeting precision and pathway engagement provide a theoretical foundation for designing precision intervention strategies tailored to specific fatigue contexts.

Humans↗

PubMed2026

Evaluating the persistence of semen under controlled environmental conditions.

When semen is deposited at a crime scene, it may be exposed to harmful environmental conditions. It is important to understand to what extent the different components of semen, specifically acid phosphatase (AP), prostate specific antigens (PSA), sperm and DNA, may become less detectable after exposure to high temperatures and varying levels of humidity. In this study, semen (50 μL) was deposited onto squares of black cotton and exposed to 45 °C and a relative humidity (RH) of 10 or 80% for 0, 7, 14, 21 or 28 days (n = 5 per day, per climate condition). Source testing included AP test reagent, ABAcard® p30 immunoassay kits, and hematoxylin and eosin staining. DNA was extracted using the DNA IQ™ System (Promega, Australia) and quantified using Quantfiler Trio™ (Thermo Fisher Scientific, Australia). Over the 28-day period under both RH conditions, the time taken for a positive AP test to develop increased significantly (p < 0.01) and the number of sperm observed decreased significantly (p < 0.01). All ABAcard® p30 tests were positive regardless of exposure time or conditions. No impact on the quantity of DNA recovered was observed when semen was exposed to 45 °C and 10% RH, with a higher median quantity of DNA recovered at day 28 compared to day 0. In contrast, when the RH was raised to 80%, the median quantity of DNA recovered was substantially less at day 28 (81.5 ng, IQR: 87.5 ng) compared to day 0 (181.5 ng, IQR: 1172.4 ng). This study highlights the impact that temperature and RH may have on the persistence of AP, PSA, sperm and DNA over time.

Humans↗

PubMed2026

Comparative genomic epidemiology of food- and patient-derived diarrheagenic Escherichia coli from sentinel surveillance in Southeast China.

Diarrheagenic Escherichia coli (DEC) remains an important foodborne pathogen, yet long-term comparative genomic surveillance data jointly characterizing food-derived and patient-derived isolates remain limited. This surveillance-based comparative study integrated antimicrobial susceptibility testing and whole-genome sequencing to characterize diarrheagenic Escherichia coli isolates recovered from food and patient sources in Lishui, Southeast China, during 2018-2025, with emphasis on occurrence, resistance profiles, genomic backgrounds, and plasmid replicon-associated features. Antimicrobial susceptibility testing was performed for 258 selected isolates, and whole-genome sequencing was conducted for a curated analytical subset of 204 isolates. The sequenced subset was used for diversity-oriented comparative genomic analysis rather than for unbiased prevalence estimation of the entire DEC collection. EAEC predominated in both sources, although food-associated occurrence was heterogeneous across categories, with the highest recovery rate observed in raw meat. Patient-derived isolates showed a broader overall resistance burden, whereas food-derived isolates retained substantial resistance to tetracycline, chloramphenicol, and florfenicol. Phylogenetic analysis showed partial overlap in genomic backgrounds between food-derived and patient-derived isolates, while representative resistance determinants displayed both broadly distributed and lineage-enriched patterns. Replicon-based plasmid profiling identified 42 plasmid types, including 12 detected in both sources, with IncF-related replicons predominating among these shared profiles. Several food-derived isolates carried multiple plasmid replicon types that were also observed in patient-derived isolates. Overall, food-derived and patient-derived DEC showed partial overlap in genomic backgrounds, resistance determinants, and replicon-defined plasmid profiles within this surveillance setting, while retaining source-associated heterogeneity. These findings should be interpreted as surveillance-based comparative evidence rather than as evidence of direct source attribution or transmission.

Humans↗

PubMed2026

Depression and amyloid-β across CSF, PET, and plasma biomarkers: a systematic review and meta-analysis.

Alzheimer's disease is increasingly defined by biomarker evidence of amyloid-β and tau pathology, sharpening questions about whether late-life depression contributes to, or instead reflects, this pathology. We conducted a systematic review and meta-analysis of studies published between 2000 and 2025 that compared amyloid-β biomarkers in adults with and without depression, with depression defined by validated clinical diagnoses or symptom rating scales. Twenty-four studies were included, spanning three biomarker sources: cerebrospinal fluid, positron emission tomography imaging, and plasma. Across all sources, the pooled difference in amyloid-β burden between depressed and non-depressed individuals was small and clustered near zero, indicating only a weak, statistically non-significant tendency toward higher amyloid in depression. When the three sources were examined separately, each yielded a similar near-null result, although between-study heterogeneity was considerable for cerebrospinal fluid and plasma and moderate for imaging. Importantly, a prespecified subgroup analysis showed that imaging results diverged by quantification method: studies using the simpler standardized uptake value ratio clustered around zero, whereas the smaller group of studies using kinetic distribution volume ratio modelling showed a significant positive association, suggesting that methodological choices critically influence the observed relationship. Taken together, these findings indicate that depression is not consistently accompanied by greater amyloid-β burden across widely used biomarker platforms. The distribution volume ratio signal nonetheless raises the possibility of subtle associations that cruder methods may obscure, and suggests that depression may shape Alzheimer's disease trajectories more by modifying the clinical impact of amyloid than by altering its amount.

Humans↗

PubMed2025

Coupling of spectroscopy and nitrogen-oxygen isotopes unveils the mechanisms of dissolved organic matter and nitrate pollution in lakes within the agro-pastoral transition zone.

Lakes in arid and semi-arid regions are subjected to severe ecological stress, such as organic pollution, eutrophication, and salinization, due to climate change and human activities. This study investigates Chagannur Lake, a typical arid-region lake that is representative and ecologically sensitive in Northern China's agro-pastoral ecotone, to uncover its pollution characteristics and mechanisms. We employed fluorescence spectroscopy and stable isotope analysis to trace dissolved organic matter (DOM) and nitrate sources. The DOM composition was dominated by microbial metabolic byproducts and protein-like substances, suggesting that microbial processes are key to organic matter transformation. Source apportionment revealed that pollutants primarily originated from livestock and poultry manure (37.6 %), agricultural fertilizers (35.6 %), and soil erosion (24.7 %), with agricultural fertilizers contributing most significantly in the Gogstai River (63.3 %). A structural equation model (SEM) coupling spectral and mass spectrometric data revealed that microbial transformation significantly impairs the lake's self-purification capacity, thereby promoting pollutant accumulation (path coefficient = 0.91,*p < 0.05). Moreover, microbial processes link endogenous and exogenous pollution, a mechanism effectively traced by isotopic and fluorescence indices (path coefficient = 0.55, ⁎⁎p < 0.01). These findings enhance the understanding of pollution sources and transformation mechanisms in arid-region lakes and offer foundational theoretical support for policymakers engaged in pollution control strategies.

Lakes↗

PubMed2025

An integrated multiscale air quality modelling framework for industrial park pollution: Linking local emissions to regional transport.

Capturing the spatiotemporal distribution of pollutants in industrial parks remains challenging for regional air quality models because of their coarse resolution (3 km), resulting in uncertainties in local emission quantification. To address this, we developed the Integrated Multiscale Air Quality Modelling System for Industry (IAQMS-Industry), coupling the regional Nested Air Quality Prediction Modelling System (NAQPMS) with a city-scale chemical transport model. This framework integrates point-source locations and Gaussian plume dispersion to simulate particulate matter with a diameter smaller than 2.5 micrometres (PM2.5) at 100 m resolution. Applied to the Beijing Yi Zhuang and Tangshan industrial parks and evaluated against observations. The coupled model achieved a normalized mean bias (NMB) ranging from 3.1 % to 6.2 %, improving upon NAQPMS (-16.9 % to -7.7 %). Spatial analysis revealed that coarse regional grids underestimated the PM2.5 concentrations at industrial sites by smoothing gradients, whereas IAQMS-Industry successfully resolved spatial patterns. Industrial point emissions accounted for 22.9 %-26.4 % of PM2.5 in the coupled model, which was significantly greater than the regional model estimates of 1.6 %-13.7 %. These findings indicate that regional models overestimate pollutant dispersion processes in industrial parks while underestimating local industrial impacts. By explicitly resolving point-source dynamics and linking them to regional transport, IAQMS-Industry provides a robust tool for designing targeted emission controls in industrial cities and balancing local air quality improvements with minimized regional pollution outflow. This study underscores the necessity of multiscale modelling for accurate source apportionment and informed environmental governance in industrial zones.

Air Pollution↗

PubMed2026

Interfacial engineering of cobalt tungstate-halloysite nanotube nanocomposite for electrochemical detection of synthetic vanillin in food matrices.

In processed foods and medicine, synthetic vanillin is widely used, although excessive intake poses toxicological risks. Due to the rising usage of synthetic vanillin in food products and associated health hazards, quick, sensitive, and reliable analytical methods are needed to precisely measure vanillin in complex food matrices. This work introduces a CoWO4@F-HNT/GCE nanocomposite as an efficient electrocatalytic modifier for glassy carbon electrodes aimed at trace-level synthetic vanillin detection. Structural and microscopic analyses confirmed phase-pure monoclinic CoWO4, preservation of the tubular aluminosilicate framework, and homogeneous nanoparticle anchoring on F-HNT. Differential pulse voltammetry provided a broad linear range from 0.01 to 372.14 μM and a low detection limit of 4.3 nM, together with excellent selectivity against common interferents, good cycling stability, and high inter-electrode reproducibility. These characteristics position the CoWO4@F-HNT-modified electrode as a cost-effective and reliable platform for on-site quality control of synthetic vanillin in complex food matrices.

Benzaldehydes↗

PubMed2026

Global prevalence and associated factors of turnover intention among intensive care nurses: A systematic review and meta-analysis.

OBJECTIVES: To estimate the global prevalence of two distinct turnover intentions among intensive care unit (ICU) nurses-intention to leave the ICU and intention to leave the nursing profession-identify significant sources of heterogeneity, and synthesise associated psychosocial factors. METHODS: Ten databases were systematically searched from inception to September 28, 2025. Two reviewers independently conducted study selection, data extraction, and quality appraisal using Joanna Briggs Institute checklists. Random-effects meta-analyses were performed to estimate pooled prevalence and associated factors. Subgroup and meta-regression analyses explored potential sources of heterogeneity. Associated factors were pooled as odds ratios (ORs) and interpreted within an integrated Job Demands-Resources and Theory of Planned Behavior framework. RESULTS: Forty-six studies published between 2007 and 2025, involving 39,246 ICU nurses, were included. The pooled prevalence was 30.7% for intention to leave the ICU and 27.5% for intention to leave the nursing profession. Significant sources of heterogeneity included ICU type, geographic region, publication year, study design, measurement tool, and sampling method. Depression, burnout, high workload, and unsafe patient-to-nurse ratios were associated with increased turnover intention, whereas positive work environments, perceived organisational support, and nursing competence were protective factors. No significant publication bias was detected. CONCLUSIONS: Turnover intention affects approximately one-third of ICU nurses globally and varies across clinical and geographical contexts. Excessive workload, inadequate organisational support, and unfavourable work environments appear to be important contributors to turnover intention among ICU nurses. IMPLICATIONS FOR CLINICAL PRACTICE: Strategies to reduce turnover intention among ICU nurses should focus on reducing excessive workload, improving staffing conditions, strengthening organisational support, and fostering positive work environments. Promoting supportive and sustainable ICU work environments may help improve nurse retention and maintain the quality of critical care services.

Humans↗

PubMed2026

Assessment of the Potential of Different Anthropometric Indices in Predicting the Risk of Diabetes and Associated Co-morbidities.

Diabetes, a chronic disorder, is showing a rapidly increasing trend globally. India holds the second position in the global diabetes epidemic. The present investigation is an assessment of different anthropometric measurements and their association with type 2 diabetes to determine their diagnostic potential for diabetes as well as its co-morbidities. In this cross-sectional study, we have measured anthropometric parameters and blood biomarkers in subjects with diabetes. We have presented the comparisons of cost- and time-effective anthropometric variable with costly and time-dependent biochemical variables in control and diabetic groups (n = 233/group). Correlations between anthropometric variables and biochemical measurements, as well as the diagnostic utility of anthropometric variables for diabetes, were evaluated. The diagnostic utility of anthropometric variables for diabetes was assessed through receiver operating characteristic (ROC) curves. Neck circumference, sagittal abdominal diameter (SAD), skinfold thickness, and body roundness index (BRI) displayed high specificity and diagnostic utility for diabetes, emphasizing their potential in predicting diabetes and the further development of metabolic syndrome. The study highlights the importance of cost- and time-effective anthropometric assessments in diabetes risk evaluation and calls for further research to elucidate this intricate relationship and develop personalized management strategies.

Humans↗

PubMed2026

A Critical Assessment of Evidence-Based Design's Knowledge Base and Inspiration: A Systematic Review.

PurposeThis study examines Evidence-Based Design (EBD) as an epistemological framework for guiding design research and practice, with a particular focus on its reliance on Evidence-Based Medicine (EBM) as a source of methodological inspiration.BackgroundOver the past two decades, EBD has been promoted as a way to strengthen design processes through the systematic use of scientific evidence. Its relationship to EBM, however, remains conceptually ambiguous: EBD draws legitimacy from EBM's hierarchical conception of "best evidence" while at the same time acknowledging the specificities of design practice, which do not easily fit such a model.MethodologyA systematic review was conducted on 31 publications in the design research literature that explicitly address the tension surrounding EBD's conception of "best evidence." The criticisms raised were coded and analyzed by main topics and subtopics.ResultsThe review highlights several reasons why EBM's hierarchical view of "best evidence" is an unsuitable epistemological foundation for EBD. It imposes scientifically inappropriate and practically ineffective methodological standards, devalues important sources of design knowledge, and fails to address central epistemic challenges intrinsic to design processes.ConclusionsBy bringing together critical yet fragmented insights from the literature, this study argues for the development of an updated epistemological framework for EBD. Constructing this framework will require sustained interdisciplinary dialogue between design research and philosophy of science.

Humans↗

PubMed2026

Mobile health apps improve Health-Related Quality of Life in Type 2 Diabetes Mellitus by enhancing medication adherence: A multicentre randomised controlled trial with mediation analysis.

AIMS: This study evaluated whether a gamified mHealth application (CareAide®) improves Health-Related Quality of Life (HRQoL) in Type 2 Diabetes Mellitus (T2DM) and whether this effect is mediated by medication adherence. METHODS: Prespecified secondary analysis of the T2DM cohort from a 6-month multicentre RCT (NCT06068309; N = 663; three Malaysian hospitals). Participants were randomised 1:1 to standard care or CareAide®. Adherence (MMAS-8), EQ-5D-5L utility (Malaysian value set), and AQoL-6D were assessed at baseline and 6 months. Simple mediation analysis (PROCESS Model 4; 5000 bootstraps) adjusted for baseline HRQoL. RESULTS: CareAide® significantly predicted higher MMAS-8 scores (mean difference +1.756; d = 1.638; p < 0.001). Higher MMAS-8 scores significantly predicted improved AQoL-6D utility (b = 0.024; p < 0.001). The direct effect on AQoL-6D was non-significant (p = 0.248). Bootstrapped indirect effect confirmed full mediation via AQoL-6D (0.042; 95% CI [0.024, 0.060]). A sensitivity analysis adjusting for baseline HbA1c confirmed full mediation (indirect = 0.034; 95% CI [0.015, 0.052]; n = 563). EQ-5D-5L utility showed a significant direct between-group difference at 6 months (p = 0.012) but did not operate as a mediation outcome. CONCLUSIONS: Medication adherence fully mediates the AQoL-6D HRQoL benefit of a gamified mHealth intervention in T2DM, as confirmed by both the primary and HbA1c-adjusted sensitivity analyses. These findings support integration of behaviourally informed digital adjuncts into routine primary diabetes care.

Humans↗

PubMed2026

Dynamics of antibiotic resistance genes co-occurrence with pathogenic and non-pathogenic bacteria throughout wastewater treatment processes.

Wastewater treatment plants (WWTPs) are recognized hotspots for antibiotic resistance genes (ARGs) and pathogenic bacteria. Despite advancements in treatment technologies, the persistence of ARGs and pathogenic bacteria remains a concern. In this study, we analyzed the dynamic changes in ARGs and bacterial communities throughout the treatment processes within an anaerobic-anoxic-oxic (AAO) WWTP over one week by using HT-qPCR coupled with 16S rRNA gene amplicon sequencing. The connectedness index, based on network analysis, showed that the dynamics of ARGs and mobile genetic elements (MGEs) were more strongly associated with potentially pathogenic bacteria than with non-pathogenic bacteria, suggesting that ARG immigration and dissemination in the WWTP were likely driven by potentially pathogenic taxa. The AAO treatment significantly reduced ARGs in final effluent (EF) (∼64 %) and residual sludge (RS) (∼81 %); however, potential hosts of ARGs such as Comamonas testosteroni and Clostridioides difficile persisted with minimal changes in relative abundance and remained detectable in EF and RS. Notably, the abundance of ARGs was lower in RS than in EF, and source tracking analysis identified influent as the primary source of ARGs and potentially pathogenic taxa in EF, underscoring the greater health risks associated with effluent discharge.

Wastewater↗

PubMed2026

Effectiveness of an AI-based home exercise app for rehabilitation of rotator cuff-related shoulder pain: A randomized controlled trial.

BACKGROUND: Rotator cuff-related shoulder pain contributes to disability and healthcare use. Although therapeutic exercise is first-line treatment, limited supervision and adherence may reduce its effectiveness; digital rehabilitation with real-time feedback may address these limitations. OBJECTIVES: To evaluate the effectiveness of adding a digital rehabilitation program to standard physiotherapy on pain, function, fear-avoidance beliefs, and healthcare utilization. DESIGN: Single-center, assessor-blinded, randomized controlled trial with two parallel groups. METHOD: Forty-six adults (mean age 59 years) with rotator cuff-related shoulder pain were randomized to 12 weeks of conventional physiotherapy or physiotherapy plus an AI-based digital rehabilitation program using computer vision for real-time feedback and performance monitoring. Outcomes were assessed at baseline and at 2, 4, and 12 weeks. Pain intensity (NPRS) was primary outcome; secondary outcomes included upper limb function (QuickDASH), fear-avoidance beliefs (FABQ), and post-intervention healthcare utilization. Analyses followed an intention-to-treat approach. RESULTS: Pain reduction exceeded the MCID (1.3) at 4 and 12 weeks. Between-group differences favoured the intervention at Weeks 2 and 4 (MD -0.7; 95% CI -1.13 to -0.14 and MD -1.01; 95% CI -1.8 to -0.2, respectively). Upper limb function improved more at Week 4 (MD -7.3; 95% CI -12.3 to -2.2). FABQ scores decreased more at Week 12 (MD -7.6; 95% CI -14 to -0.5). Fewer participants in the experimental group required post-intervention healthcare (3 vs 10; p = 0.02). CONCLUSION: Adding AI-based home exercise app to conventional treatment improve pain and may improve function and reduce healthcare utilization in rotator cuff-related shoulder pain.

Humans↗