External stimuli-responsive drug delivery to the posterior segment of the eye

Posterior segment eye diseases represent the leading causes of vision impairment and blindness globally. Current therapies still have notable drawbacks, including the need for frequent invasive injections and the associated risks of severe ocular complications. Recently, the utility of external stimuli, such as light, ultrasound, magnetic field, and electric field, has been noted as a promising strategy to enhance drug delivery to the posterior segment of the eye. In this review, we briefly summarize the main physiological barriers against ocular drug delivery, focusing primarily on the recent advancements that utilize external stimuli to improve treatment outcomes for posterior segment eye diseases. The advantages of these external stimuli-responsive drug delivery strategies are discussed, with illustrative examples highlighting improved tissue penetration, enhanced control over drug release, and targeted drug delivery to ocular lesions through minimally invasive routes. Finally, we discuss the challenges and future perspectives in the translational research of external stimuli-responsive drug delivery platforms, aiming to bridge existing gaps toward clinical use.published_or_final_versio

Exploring Humanities Education in Chinese Dental Schools: Perspectives From Faculty Members and Students

Objective: To evaluate the status quo of humanities education in Chinese dental institutions and identify improvement areas. Methods: A nationwide cross-sectional study across 20 representative Chinese dental institutions employed survey questionnaires developed through literature review and expert consultations. The questionnaire included a visual analogue scale satisfaction assessment, multiple-choice questions, and open-ended questions supplemented by the Chinese Jefferson Scale of Empathy for students. Responses from students, faculty members, and administrators of each school were analysed to evaluate current practices and improvement opportunities. Results: A total of 5085 dental students, 2044 faculty members, and 20 administrative staff from 20 dental institutions completed the questionaries. Both cohorts identified the curriculum design and teaching delivery mode as the most unsatisfactory aspects of current humanities education. Specifically, students emphasized the need for longitudinal integration of humanities content throughout dental education. Satisfaction levels varied significantly by students ‘academic progression and faculty members’ career stage. Female dental students consistently demonstrated higher empathy scores than males (P published_or_final_versio

Neural connectivity biotypes: Predictors of clinical outcomes and improvement patterns of iTBS treatment in adolescents and young adults with depression

Background The heterogeneity of depression limits the treatment outcomes of intermittent theta burst stimulation (iTBS) and hinders the identification of predictive factors. This study investigated functional network connectivity and predictors of iTBS treatment outcomes in adolescents and young adults with depression. Aim This study aimed to identify default mode network (DMN)-based connectivity patterns associated with varying iTBS treatment outcomes in depression. Methods Data from a randomised controlled trial of iTBS in depression (n=82) were analysed using a data-driven approach to classify homogeneous subgroups based on the DMN. Connectivity subgroups were compared on depressive symptoms and cognitive function at pretreatment and post-treatment. Furthermore, the predictive significance of baseline inflammatory cytokines on post-treatment outcomes was evaluated. Results Two distinct subgroups were identified. Subgroup 1 exhibited high heterogeneity and greater centrality in the posterior cingulate cortex and retrosplenial cortex, while subgroup 2 showed more homogeneous connectivity patterns and greater centrality in the temporoparietal junction and posterior inferior parietal lobule. No main effect for subgroup, treatment or subgroup×treatment interaction was revealed in the improvement of depressive symptoms. A significant subgroup×treatment interaction related to symbol coding improvement was detected (F=5.22, p=0.026). Within subgroup 1, the active group showed significantly greater improvement in symbol coding compared with the sham group (t=2.30, p=0.028), while baseline levels of interleukin-6 and C-reactive protein emerged as significant indicators for predicting improvements in symbolic coding (R 2 =0.35, RMSE (root-mean-square error)=5.72, p=0.013). Subgroup 2 showed no significant findings in terms of cognitive improvement or inflammatory cytokines predictions. Conclusions Data-driven network analyses offer valuable insights into iTBS treatment outcomes in depression, providing clues for predicting cognitive improvements from an inflammatory perspective.</p

Common and rare variant analyses implicate late-infancy cerebellar development and immune genes in ADHD

ObjectiveAttention-deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder with a significant genetic component. The latest genome-wide association study (GWAS) meta-analysis of ADHD identified 27 whole-genome significant risk loci in the European population. However, genetic risk factors for ADHD are less well-characterized in the Asian population, especially for low-frequency / rare variants.MethodsIn this study, we aimed to investigate the contributions of both common and low-frequency / rare variants to ADHD in a Hong Kong sample. Our sample comprised 279 cases and 432 controls who underwent genotyping using the Illumina Infinium Global Screening Array. We employed various analytical methods at different levels, while also leveraging multi-omics data and large-scale summary statistics to comprehensively analyze the genetic basis of ADHD.ResultsWe identified 41 potential genomic risk loci with a suggestive association (p −4), pointing to 111 candidate risk genes, which were enriched for genes differentially expressed during late infancy brain development. Furthermore, tissue enrichment analysis implicated the involvement of the cerebellum. At the polygenic level, we also discovered a strong genetic correlation with resting-state functional MRI connectivity of the cerebellum involved in the attention/central executive and subcortical-cerebellum networks. In addition, an accumulation of ADHD common-variant risks found in European ancestry samples was found to be significantly associated with ADHD in the current study. In low-frequency / rare variant analyses, we discovered the correlations between ADHD and collapsing effects of rare damaging variants in TEP1, MTMR10, DBH, TBCC, and ANO1. Based on biological and functional profiles of the potential risk genes and gene sets, both common and low-frequency / rare variant analyses demonstrated that ADHD genetic risk was associated with immune processes.ConclusionsThese findings re-validate the abnormal development of the neural system in ADHD and extend the existing neuro-dysfunction hypothesis to a multi-system perspective. The current study identified convergent risk factors from common and low-frequency / rare variants, which implicates vulnerability in late-infancy brain development, affecting especially the cerebellum, and the involvement of immune processes.published_or_final_versio

Seven principles for effectively partnering with Generative AI for teaching and learning

The rapid advancement of Generative Artificial Intelligence (AI) has ushered in both unprecedented opportunities and challenges within the realm of higher education, particularly in the context of English language teaching. This article delineates seven foundational principles that aim to optimize the integration of Generative AI in teaching and learning environments. Developed from the practical experiences of frontline language teachers at Hong Kong universities, these principles advocate for a paradigm shift in the perception and utilization of AI—from viewing it merely as a tool for information retrieval to recognizing it as a robust collaborator capable of enhancing cognitive development and interaction.These principles emphasize the importance of leveraging AI's capabilities to foster a more interactive and dynamic educational experience. They address the need to prioritize AI as a reasoning engine, ensure the quality of data inputs, customize AI interactions, actively harness AI to simulate human textual interactions, and focus on ethical AI usage, among others. By implementing these principles, educators can transform AI into a powerful ally that not only streamlines educational processes but also significantly enriches learning outcomes. This approach prepares students to adeptly navigate and analyze the complex information landscapes of their academic and professional futures, thus making AI an essential partner in education. The article serves as a call to action for educators to engage deeply with AI technologies, proposing a thoughtful framework that fosters enhanced educational practices and prepares students for a digitally integrated world.</p

A multi-scale crystal-plasticity finite-element framework coupled with efficient and minimalist continuum dislocation dynamics

A long-standing challenge in computational crystal plasticity is to develop models for capturing real-sized stress-strain responses from detailed enough dislocation physics at the meso-scale. In this work, a multiscale crystal-plasticity finite-element, continuous dislocation dynamics (CDD) framework is constructed to meet this objective. In this framework, a finite-element method (FEM) is used to compute the macroscopic stress field at the resolution scale of the macro element, from the imposed boundary displacement and the plastic strain due to dislocation motion. The latter is computed at the CDD level by considering the dynamics of an ‘all-dislocation’ density driven by the FEM-level stress field from the applied loading, and the internal stress field due to mutual dislocation interactions at a mesoscopic resolution scale. Test cases of single- and multiple-element FEM for single- and poly-crystalline models of the face-centered crystal structure are studied under tensile, compressive and shear loading conditions, and the results indicate the expected flow anisotropy, stress concentration and plastic instability in these scenarios. This work is an important step towards building physics-based finite-element crystal plasticity models for simulating real-scale elasto-plasticity in metals and alloys

Impact of the baby friendly community initiative on breastfeeding outcomes: A systematic review and meta-analysis

Objective: To examine the impact of the Baby Friendly Community Initiative (BFCI) on breastfeeding outcomes worldwide, specifically the duration of any and exclusive breastfeeding, compared to standard maternal care. Methods: A systematic review and meta-analysis were conducted. Seven electronic databases were searched from November 1998 to July 2024. Quantitative studies examining the effects of BFCI on breastfeeding outcomes were included. The quality of included studies was assessed using the Cochrane risk of bias tools and NHLBI study quality assessment tools. Narrative synthesis was performed for studies not suitable for meta-analysis. Results: Out of 14,495 identified records, 13 were included after the removal of duplicates and ineligible articles. The majority of included studies found that BFCI, whether implemented partially, fully or in combination with other initiatives, is an effective intervention for improving breastfeeding outcomes. The meta-analysis showed an increase prevalence of exclusive breastfeeding at 6 months postpartum in BFCI group (OR=4.00; 95 % CI 1.29–12.38, P = 0.02). Further studies are needed to investigate the statistical significance of BFCI on any breastfeeding from 6 months to 2 years postpartum. Discussion: BFCI has the potential to significantly enhance long-term exclusive breastfeeding rates and may also improve any breastfeeding rates from 6 months onward. However, the nature of BFCI implementation posed limitations to study design, which reduced the overall methodological quality of the included studies.</p

Lymphocyte nadir and recovery dynamics for locally advanced thoracic malignancies undergoing concurrent chemo-irradiation: Establishment of organs-at-risk constraints

Background and purpose: Radiotherapy-induced-lymphopenia (RIL) worsens outcome in thoracic malignancies on radiotherapy (RT). We hypothesised that post-RT absolute lymphocyte count (ALC) nadir and recovery were independently prognostic for overall survival (OS) and progression-free survival (PFS) in thoracic malignancies following radical chemo-irradiation. We also aimed to determine relevant organs-at-risk (OARs) constraints. Methods and materials: Two independent cohorts of stage III non-small-cell lung cancer (NSCLC) and stage II to III oesophageal cancer (EC) patients receiving chemo-irradiation from 2013 to 2022 were analysed. ALC nadir was defined as the lowest ALC on RT. ALC recovery index (ARI) was the ALC at 6 months/Pre-RT ALC. Effect of ALC nadir and ARI on OS and PFS were evaluated. RT dose of OARs was correlated with ALC nadir and ARI. OAR thresholds were then determined. Results: High ARI and ALC nadir were independently prognostic of improved OS and PFS for both cohorts. In NSCLC, thoracic spine V35Gy and ribs V35Gy were associated with ARI. Cut-off for thoracic spine V35Gy was 25.5 % while ribs V35Gy cut-off was 6.6 %. Thoracic spine V20Gy and Mean lung dose (MLD) were associated with ALC nadir in NSCLC. MLD cut-off was 16.5 Gy while T spine V20Gy cut off was 25.6 %. For EC, thoracic spine V35Gy was also associated with ARI. Similar to NSCLC, cut-off was 25.7 %. MLD and spleen V5Gy were associated with ALC nadir. MLD and Spleen V5Gy cut-off was 10.6 Gy and 7.2 % respectively. Conclusion: Post-RT lymphocyte nadir and recovery were both important for survival outcomes. Future prospective studies are warranted to validate whether abiding to lymphocyte sparing OARs constraints developed in the current study can improve lymphopenia and outcomes

Next-Generation Biomaterials for Vital Pulp Therapy: Exploring Biological Properties and Dentin Regeneration Mechanisms

The advancement of Vital Pulp Therapy (VPT) in dentistry has shown remarkable progress, with a focus on innovative materials and scaffolds to facilitate reparative dentin formation and tissue regeneration. A comprehensive search strategy was performed across PubMed, Scopus, and Web of Science using keywords such as “vital pulp therapy”, “biomaterials”, “dentin regeneration”, and “growth factors”, with filters for English language studies published in the last 10 years. The inclusion criteria focused on in vitro, in vivo, and clinical studies evaluating traditional and next-generation biomaterials for pulp capping and tissue regeneration. Due to the limitations of calcium-based cements in tissue regeneration, next-generation biomaterials like gelatin, chitosan, alginate, platelet-rich fibrins (PRF), demineralized dentin matrix (DDM), self-assembling peptides, and DNA-based nanomaterials were explored for their enhanced biocompatibility, antibacterial properties, and regenerative potential. These biomaterials hold great potential in enhancing VPT outcomes, but further research is required to understand their efficacy and impact on dentin reparative properties. This review explores the mechanisms and properties of biomaterials in dentin tissue regeneration, emphasizing key features that enhance tissue regeneration. These features include biomaterial sources, physicochemical properties, and biological characteristics that support cells and functions. The discussion also covers the biomaterials’ capability to encapsulate growth factors for dentin repair. The development of innovative biomaterials and next-generation scaffold materials presents exciting opportunities for advancing VPT in dentistry, with the potential to improve clinical outcomes and promote tissue regeneration in a safe and effective manner.published_or_final_versio

Cold atmospheric plasma combined with nanoparticles in cancer therapy

This review explores the application of cold atmospheric plasma (CAP) and nanoparticles (NPs) in cancer therapy, highlighting their potential to enhance treatment efficacy and minimize side effects. CAP generates reactive oxygen and nitrogen species that selectively induce apoptosis in cancer cells, while NPs improve drug delivery, enhance targeting precision, and reduce adverse effects on healthy tissues. By summarizing various types of NPs, including gold, silver, magnetic, and other NPs, we evaluate their individual and combined effects with CAP across different cancer models. Our findings suggest that combined CAP-NPs significantly enhance therapeutic outcomes by increasing cancer cell sensitivity and minimizing damage to surrounding tissues. This synergistic approach not only aligns with previous research on CAP's selective toxicity but also reveals new possibilities for optimizing cancer treatment through targeted NP delivery. Further clinical research is needed to establish the safety and efficacy of this combination, paving the way for novel, patient-specific treatment strategies with improved outcomes.</p