Browse Articles

Multicentre gene therapy for OTOF-related deafness followed up to 2.5 years

Novel class of population mean estimators based on robust regression methods

One year of hyperglycemia in the Ins2Akita mouse does not impart changes in retinal vascular patterning

Diabetic retinopathy (DR) is one of the leading causes of blindness often associated with retinal vascular pathology in humans. To aid our understanding of DR, the Ins2 Akita mouse has served as a type 1 diabetes model. These mice have sustained elevated blood glucose (BG) and we tracked microvascular changes in the retinal circulation for up to one year. Retinal flat mounts of male Ins2 Akita x NG2DSRed (n = 14) mice age 7–61 weeks were imaged using a confocal microscope and compared to age matched euglycemic mice (n = 13) to establish a ground-truth of vascular patterning. We analyzed vessel density, vessel branching, vessel length, tortuosity, pericyte density, and the connectivity between vascular plexuses at eccentricities up to 2 mm from the optic disc. An additional hyperglycemic mouse was longitudinally imaged using an adaptive optics scanning light ophthalmoscope (AOSLO) for 12 weeks from 24–36 weeks of age. We found that up to one year of hyperglycemia had minimal impact on these retinal vasculature metrics that are also accessible to in vivo ophthalmoscopy. The longitudinally imaged mouse showed no changes and high congruence with ex vivo data. We conclude that yearlong elevated blood glucose did not impart detectable changes in retinal microvascular patterning.

Optimized recycling of e-waste and tire rubber into sustainable polyurethane composites with enhanced compressive performance

Abstract Research on reusing industrial and electronic waste in functional composite systems has been spurred by the growing need for sustainable engineering materials. This study used methylene diphenyl diisocyanate (MDI) as a binder to reinforce three recycled fillers: waste rigid polyurethane foam (WRPU), rubber tire waste (RTW), and waste printed circuit boards (WPCB). Response Surface Methodology (RSM) optimization revealed that the optimal composition was 6 wt% WRPU, 3 wt% RTW, and 7.58 wt% WPCB. With a maximum compressive strength of 38.987 MPa, this optimized formulation showed significant improvement over the unreinforced matrix (14.128 MPa). The mechanical performance was highly precisely validated by numerical simulation using ANSYS Workbench, with a deviation from the experimental results of only 0.75%. FTIR and thermogravimetric analysis (TGA) indicated enhanced interfacial interactions, improved compatibility and thermal stability up to 550 °C, while high-resolution scanning electron microscopy (HR-SEM) verified uniform filler distribution. By enhancing interfacial bonding and stress transfer efficiency, the synergistic interaction of WRPU, RTW, and WPCB clarified the structure–property relationship controlling composite performance. These results support a sustainable circular economy by showcasing the potential of recycled polyurethane composites for lightweight, compressive load-bearing applications in automotive non-structural components.

Editorial Note: Towards secure and efficient integration of blockchain and 6G networks

Dynamic path optimization and multi-objective decision-making for photovoltaic tracking systems using deep reinforcement learning

Comparison of altruistic, egoistic, and scientific appeals in the recruitment of politicians to a survey panel

Low survey participation is a persistent problem for all survey researchers. Unlike citizens, politicians are seldom targeted for surveys. Politicians often are not prepared to participate, which leads to a lack of understanding regarding their willingness to collaborate in surveys. This study presents a rare survey recruitment experiment where 7,397 local-level politicians from Finland were randomly assigned to groups that received by e-mail 1) an altruistic or 2) an egoistic appeal or 3) an appeal referring to benefits for science when they were invited to participate in the Finnish Politician Panel. Overall, we find no differences in collaboration rates, suggesting that in politician samples the altruism-egoism framework is largely irrelevant and that for maximizing participation rates among politicians, survey researchers should look into alternative methods. However, politicians who are older, live in urban municipalities and represent the political left are more likely than their counterparts to volunteer as panel participants.

Electric dipole moment drives the dynamics of the TNFR1 complex I signalosome

Reported trust varies with graded value alignment in AI-attributed economic–environmental choices

Exfoliating effect of β-glycyrrhetinic acid on plaque inducing gingivitis: Comparison with cetylpyridinium chloride

β-glycyrrhetinic acid (BGA) possesses antibacterial effects against human supragingival plaque bacteria and inhibits biofilm formation. However, the effect of BGA on already formed dental plaque has not been investigated. We analyzed and compared the effects of BGA on preformed supragingival plaque biofilms with those of cetylpyridinium chloride (CPC). All experiments were performed in vitro using biofilms formed by incubating supragingival plaque bacteria for 24 h. First, we analyzed the number of viable and dead bacteria in the biofilms following BGA and CPC application. The number of viable bacteria was significantly reduced by BGA treatment compared with by the solvent control. However, the viable/dead bacterial ratios did not significantly vary. Conversely, the turbidity in the supernatants (optical density at 600 nm [OD 600 ]) was 0.237 ± 0.003, 0.136 ± 0.002, and 0.096 ± 0.002 for the BGA, CPC, and solvent control groups, respectively, indicating superior ability of BGA in biofilm exfoliation. This study suggests that BGA may inhibit dental plaque adhesion and eliminate and disinfect dental plaque through a mechanism different from CPC, contributing to the prevention of periodontal disease.

Cracking the CODEX of the leukemic BM microenvironment

Association of combined waist-to-height ratio and systolic blood pressure categories with incident cardiovascular disease in middle-aged and older adults

Abstract Cardiovascular disease (CVD) is the leading cause of global mortality. Early identification of individuals at higher risk of CVD is important for prevention and management. Traditional cardiovascular risk assessment approaches often require laboratory testing and related infrastructure, which may limit their implementation in community settings. This prospective cohort study examined the association of combined waist-to-height ratio (WHtR) and systolic blood pressure (SBP) categories with incident CVD in middle-aged and older adults. We analyzed 6,770 adults aged ≥ 45 years without baseline CVD from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2018). Participants were categorized by WHtR (≥ 0.5/<0.5) and SBP (≥ 140/<140 mmHg). Cox proportional hazards models were used to assess associations with incident CVD, adjusting for sociodemographic, lifestyle, and metabolic covariates. Over 7 years of follow-up, 1,384 CVD events occurred. Elevated WHtR alone (HR = 1.271, 95% CI: 1.111–1.455) and elevated SBP alone (HR = 1.392, 95% CI: 1.240–1.564) were each associated with a higher risk of incident CVD. Participants with concurrent elevations in WHtR and SBP had a 68.2% higher risk of incident CVD (HR = 1.682, 95% CI: 1.417–1.996) compared with those with normal values. These associations remained consistent across subgroup and sensitivity analyses. Combined WHtR and SBP categories may offer a simple, low-cost approach for community-based cardiovascular risk stratification in middle-aged and older adults. Requiring only a tape measure and a sphygmomanometer, this approach may help identify individuals at higher risk of incident CVD in settings where laboratory testing is less accessible.

Tissue scaffold architecture affects implant degradation and bone tissue regeneration: A novel in silico mechanobiological model analysing cell behavior, mechanical stress and degradation kinematics

Synthetic bone tissue scaffold function is controlled by both material and architecture. Experimental biomaterial approaches have brought significant advances in scaffold function, but scaffold architecture has not been fully explored. There are many scaffold architecture design options which could be more efficiently evaluated using computational methods. The aim of this study is to introduce a novel mechanobiological computational model to assess the effect of implant degradation, bone formation, and the influence of bone loading. A finite element model of a synthetic bone tissue scaffold within a rat bone defect supported by a fixation plate was coupled with an agent-based cell and degradation model (both bulk and surface degradation). The approach was partially validated using in vivo experimental mass-loss data and tested in a case study examining four poly-L-lactic acid tissue scaffolds with varying architectures. The model was run for 90 days to calculate results on cell behaviour, tissue formation and scaffold degradation. The results showed that scaffold architecture strongly influences degradation and cellular behaviour, with a filament thickness of 0.6 mm yielding 39 mm³ of new bone formation compared to 18 mm³ in a filament thickness of 0.2 mm, representing an approximate 117% increase at day 90. Cell migration was increased in higher porosity scaffold architectures by 31% when changing from 20.9% (T4) to 54.7% (T1) porosity. The mechanobiological computational model is, to the authors’ knowledge, the first time that implant degradation kinetics, mechanical environment, and cellular behavior have been combined in an in silico approach. The results show the importance of scaffold architecture design in the function of bone healing aided by tissue scaffold technology, emphasizing the importance of shape as well as material to improve implant function. Future work should aim to improve degradation modelling to include localised pH, autocatalysis and varying degradation rates due to chemical changes. Additionally, models should also include angiogenesis to account for the importance of revascularization in bone healing.

CSNK1E sustains stemlike drug persistence in diffuse large B-cell lymphoma

Abstract Relapsed or refractory (R/R) disease occurs in up to 40% of patients with diffuse large B-cell lymphoma (DLBCL) following first-line immunochemotherapy. However, the molecular mechanisms underlying drug persistence remain incompletely defined. In this study, we performed single-cell RNA and B-cell receptor sequencing on paired diagnostic and R/R samples from 8 patients who were either treatment-refractory or relapsed after remission, and validated our findings in 3 independent patient cohorts. We found that drug-persistent cells exhibited a transcriptional profile indicative of a less-differentiated state and adopted a memory B-cell–like program with enhanced stemlike properties, which correlated with unfavorable clinical outcomes across multiple DLBCL cohorts. Functionally, drug-persistent cells showed significantly increased in vitro clonogenicity and in vivo tumor-initiating capacity. Mechanistically, the WNT signaling regulator casein kinase 1ɛ (CSNK1E) was upregulated in these stemlike drug-persistent cells, in part through the activation of the A proliferation-inducing ligand (APRIL)–TNFRSF13B axis. Notably, CSNK1E inhibition impaired the growth and tumor-initiating capacity of drug-persistent cells and potentiated the efficacy of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)–based treatment, both in vitro and in vivo. Together, our study reveals the stemlike transcriptional and functional properties of drug-persistent cells, and identifies CSNK1E as a critical mediator and therapeutic vulnerability that may improve the efficacy of standard immunochemotherapy in DLBCL.

EEG-based stress classification using time-domain features and segmentation techniques

Abstract Stress has been recognized as a significant global health issue, affecting the majority of the population. Rapid and accurate detection of stress is critical for stress treatment. A considerable part of prior work has focused on classifying electroencephalography signals to enable preliminary detection of stress. Previous work has demonstrated considerable success in stress classification/detection using electroencephalography signals. The proposed work aims to classify human stress using electroencephalography signals to enable early intervention. In this research, we have worked with a dataset comprising nearly 211 individuals and proposed a method based on time-domain analysis. Segmentation techniques are used to analyze stress from EEG signals. Both overlapping and non-overlapping methods are employed in this research work. The EEG signals last approximately 480 seconds. We have used the Perceived Stress Questionnaire (PSQ) for the labeled classes of ‘stressed’ and ‘non-stressed’. Different classifiers have been employed to distinguish between stressed and non-stressed classes. Our proposed method achieved an accuracy of 96.32% using a K-nearest neighbors classifier with a non-overlapping segmentation technique.

Anti-inflammatory and immunomodulatory potential of lignans from Artemisia cina: Integrated quantum, docking, and cytokine expression studies

Quantum, docking, and in vitro studies were performed to evaluate the immunomodulatory function of two lignans isolated from Artemisia cina —3-demethoxy-6-O-demethylisoguaiacin ( L1 ) and norisoguaiacin ( L2 )—through individual molecular docking with cyclooxygenase-2 (COX-2) and their mixture for cytokine assays. The structures of L1 and L2 were optimized using density functional theory with the B3LYP/6–311++G(d,p) method. The optimized structures were then docked into the COX-2 active site, revealing slightly lower binding affinities (ΔG = −7.57 and −7.13 kcal/mol, respectively) compared with naproxen (−8.95 kcal/mol). The interactions of the ligands with Ser530 and Arg120 in the arachidonate-binding site predict a potential COX-2 inhibition through π-donor hydrogen interactions, along with several hydrophobic and π–π interactions. In the in vitro assays, both lignans significantly upregulated the anti-inflammatory cytokines interleukin (IL)-6, IL-4, and IL-13, which are involved in host protection against nematodes. By contrast, the chemokine CXCL8 was downregulated, indicating a reduction in inflammatory signaling. Moreover, the combination of L1 and L2 with lipopolysaccharide showed a synergistic effect, increasing the relative expression of IL-13 (212.8-fold), highlighting their immunomodulatory activity. These findings from in silico and in vitro assays suggest that the lignans could have potential anti-inflammatory effects, but direct evidence of COX-2 enzymatic inhibition is still lacking. Further in vivo studies are warranted to validate their therapeutic potential. Further in vivo studies are warranted to validate their therapeutic potential.

A reassessment of anti–CAR T-cell expansion strategies

Punctuated decline of human cooperation

Abstract Human cooperation is dynamic and often declines even under favourable conditions 1–4 . Many prevailing theories explain the decrease of cooperation in terms of strategic behaviour or learning, framed as evidence of rational behaviour or progression towards rationality 5–9 . Here we show that a key source of long-term decline derives from deviations from rational behaviour that systematically vary over time. We analyse a natural social dilemma in the field—that is, group lending in Sierra Leone—tracking cooperative dynamics over a five-year period. Borrowers enter a joint-liability contract, structured so that if the group loan is not repaid in full, all members lose access to future credit 10 . This produces a threshold social dilemma with incentives to free-ride 11,12 . The dataset includes 47,931 group payments made by 7,108 borrowers, augmented with a two-stage cluster sample of semi-structured interviews. We find a statistically robust pattern of punctuated decline driven by behavioural mechanisms 13 . Cooperation rates start out high but gradually decline due to decreases in group members’ cooperative motivation and effort. Sharp rebounds occur when loans are restarted and clients resensitized to their cooperative responsibilities, even though the group membership and dilemma structure are largely unchanged. This pattern persists over the five-year observation window, but with each successive restart the subsequent decline is more rapid. The findings have direct implications for preventing behavioural decline in cooperative programmes and institutions.

Prevalence and associated factors of diabetic foot ulcer among patients with diabetes mellitus in Eastern Sudan: A cross-sectional study

Accuracy of sarcopenia screening tools among older adults with stroke undergoing inpatient rehabilitation

Background Appropriate screening tools for sarcopenia are available for older adults with stroke undergoing inpatient rehabilitation, however how well these tools predict and eventually diagnose sarcopenia remain unknown. Objective To investigate the accuracy of five index tools including calf circumference (CC), the strength, assistance with walking, rising from a chair, climbing stairs and falls (SARC-F), the CC combined with SARC-F (SARC-CalF), the 5-item and 7-item Mini Sarcopenia Risk Assessment (MSRA-5 and MSRA-7) for screening sarcopenia among older adults with stroke undergoing inpatient rehabilitation according to the guideline from the Asian Working Group for Sarcopenia 2019. Methods Stroke patients aged sixty years and older who admitted for inpatient rehabilitation were included between April 2023 and June 2024. In this study, sarcopenia was defined by low skeletal muscle mass and low grip strength. Skeletal muscle mass was evaluated using a bioelectrical impedance analysis. Grip strength was assessed using a digital handheld dynamometer. The five index tests were applied. Diagnostic indices and areas under the receiver operating characteristic curves (AUC) were analyzed. Youden’s index was used to determine the optimal cut-off values for the index tests. Results One-hundred and fourteen patients with stroke were included (55.26% male) with mean age of 70.39 years. The prevalence of sarcopenia was 50.88%. The AUC with 95% confidence interval of CC, SARC-F, SARC-CalF, MSRA-5 and MSRA-7 were 0.873 (0.797–0.928), 0.653 (0.558–0.740), 0.832 (0.751–0.896), 0.641 (0.546–0.729), and 0.626 (0.530–0.715), respectively. The optimal cut-off points of the CC were < 33 cm for men, and < 32 cm for women, and the optimal cut-off point of SARC-CalF was ≥ 16. Conclusions The CC and SARC-CalF were demonstrated appropriate diagnostic performance for screening sarcopenia in older adults with stroke undergoing inpatient rehabilitation.