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Black communities account for a hugely disproportionate and increasing burden of Canada's HIV epidemic. According to the Public Health Agency of Canada, Black people made up 27% of new HIV cases in 2023 even though, according to the census of Canada, slightly less than 5% of the country's population identifies as Black. Moreover, Black people have an elevated risk of dying from AIDS compared to white Canadians. This disproportionality has been building for the last 40 years, but the research and policy communities have not responded with the urgency, imagination, or resources that the crisis warrants. Evidently, health and research policy have failed Black communities. In 2022, the Interim Committee on HIV among Black Communities in Canada developed the Black HIV Manifesto in support of its self-determined, community-focussed, evidence-informed advocacy to address the crisis of HIV affecting Black communities. In this paper, we explicate the concept of 'Black Emancipation' as a transformational framework, orientation and goal for understanding and responding to HIV and related inequities among Black communities. We underline a distinction between legal emancipation in the 19th century (1830-1880 s) and the prolonged systemic amputation of Black livelihoods up to the present, and discuss how HIV-related public health and research policy may be implicated in reproducing inequities in health and wellbeing. Finally, we identify new directions that foreground critical community-focussed scholarship and practice to change the trajectory of HIV among Black communities.

To assess the methodological quality of cardiac CT and MRI radiomics studies using the METhodological RadiomICs Score (METRICS) and Radiomics Quality Score (RQS), and to evaluate inter-rater reliability (IRR) of both scoring tools among human readers and ChatGPT 5.1 Thinking. Cardiac CT and MRI radiomics studies published up to 28 February 2025 were scored by human readers with complementary expertise in cardiac imaging and radiomics using both scoring systems. IRR was evaluated in 30 randomly selected studies by two independent groups of secondary readers and ChatGPT 5.1 Thinking. Of 781 screened records, 154 were included. The overall median METRICS was 0.60 (IQR, 0.52-0.68), and the median percentage RQS was 0.36 (IQR, 0.19-0.42), corresponding to a median absolute RQS of 13 (IQR, 8-15). The scoring systems highlighted several methodological limitations, such as a lack of external validation, a prospective study design, and open data availability. Between human readers, IRR was good for METRICS (ICC, 0.77-0.88) and moderate to good for RQS (ICC, 0.59-0.82). Between human readers and ChatGPT 5.1 Thinking, IRR was moderate to good for METRICS (ICC, 0.70-0.85) but only poor to moderate for RQS (ICC, 0.46-0.56). Cardiac CT and MRI radiomics research quality was rated as good by METRICS, whereas RQS yielded lower scores. Human readers showed good reproducibility with METRICS and moderate to good reproducibility with RQS. ChatGPT 5.1 Thinking showed potential for automating the evaluation process, but its use requires caution due to potential discrepancies with human evaluations. Research quality in cardiac CT and MRI still suffers from substantial limitations. The application of METRICS and RQS using LLMs requires caution, given the limited reproducibility when compared with human assessments. According to METRICS and RQS, radiomic-based cardiac CT and MRI studies remain affected by substantial methodological limitations. Human readers achieved good reproducibility with METRICS and moderate to good reproducibility with RQS. ChatGPT 5.1 Thinking may be helpful for scoring radiomics research quality, but its results should be interpreted with caution due to potential discrepancies with human evaluations.

Parents of children with achondroplasia face sustained caregiving demands that may affect multiple dimensions of well-being. Despite growing recognition of these challenges, no validated, condition-specific instrument exists to assess the quality of life (QoL) of parents of children with achondroplasia. This study aimed to develop, and pilot test the Quality of Life of Parents of Children with Achondroplasia (QOLA) questionnaire. QOLA was developed using a multi-phase mixed-methods design in accordance with established standards for developing self-reported outcome measures for caregivers and parents. Phase 1 comprised semi-structured qualitative interviews with 17 parents of children with achondroplasia to identify relevant QoL domains and language. Interview data were analysed using qualitative content analysis and informed systematic item generation (Phase 2). Conceptual structure was examined through researcher-led card sorting (Phase 3) and two rounds of international card sorting following translation (Phase 4). The resulting 63-item questionnaire across eight domains was pilot-tested in a cross-sectional, multi-country study with embedded cognitive debriefing in Germany, Italy, and Portugal (total N = 50). The final pilot version of QOLA comprised 63 items across eight domains covering healthcare experiences, challenges and support, physical health, mental health, social life and relationships, coping, family and daily life, and worries and future concerns. Item-level missing data were minimal, and no pronounced floor or ceiling effects were observed. Internal consistency was acceptable to good for domains (α = 0.624-0.821) and good for the total scale (α = 0.798). Inter-domain correlations were generally moderate to strong. Cognitive debriefing was highly acceptable and relevant across countries, with some suggestions for further refinement. QOLA shows strong preliminary evidence of acceptability and internal consistency and addresses a key measurement gap in achondroplasia research. Further large-scale psychometric validation is warranted.

Learning about conflicts of interest should be one of the core aspects aspect of clinical ethics in undergraduate and postgraduate training. However, the focus may direct more to external factors such as ties with, or inducements from, pharmaceutical interests rather than inherent fallibilities and motives of practitioners. At first sight it would appear that there is very limited concentration on the impact of income or private versus public practice on clinical practice in ethics textbooks. A list of clinical/medical ethics textbooks available on open shelves was established in the libraries of Trinity College Dublin, a deposit library alongside Oxford and Cambridge, each of which has rights to a copy of all publications originating in the British Isles. Two researchers independently established the presence and proportion of text relating to income or private practice in each textbook. In cases of disagreement, the senior author adjudicated. Descriptive statistics were used. Of 123 ethics textbooks examined, 304 out of 38,410 pages (mean 2.5 (0.89%), standard deviation 1.73, median 0) were dedicated to the issue of income and private practice. Leaders in clinical ethics should devote more emphasis to scrutiny and debate on the impact of income in addition to private and dual practice in education and research. There is significant opportunity to enhance such teaching by incorporating an informed approach to the wit and wisdom of the reflections on doctors and their income by Plautus, Molière and GB Shaw.

Regulatory agencies may require industry sponsors of new drugs or biologics to conduct clinical trials that assess the benefits versus the risks of these new medicines in pediatric patients as a means of facilitating their development and availability for children when there is a medical need. Amgen Inc. (henceforth "the company") agreed to conduct a randomized, controlled trial (RCT) in pediatric subjects with Glucocorticoid-induced Osteoporosis (GiOP) under a Paediatric Investigation Plan (PIP) and Pediatric Study Plan (PSP) with the European Medicines Agency (EMA) and the United States (US) Food and Drug Administration (FDA), respectively, as one of the pediatric studies that were a condition of registration for Prolia (denosumab). Enrollment of pediatric subjects with GiOP into the agreed clinical study was exceedingly low despite the implementation of multiple mitigation measures. As a result, the company explored the use of real-world epidemiological analyses of the disease in children with GiOP for further insight into the clinical feasibility challenges with the RCT design. We initiated a phase 3 randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of denosumab in pediatric subjects with GiOP (Study 20140444). Following difficulties in recruiting we re-assessed the enrollment potential and overall clinical trial feasibility of Study 20140444 using real-world epidemiological analyses evaluating the size of the pediatric GiOP population using real-world data (RWD) from 3 different databases: (1) the US MarketScan, (2) the United Kingdom (UK) Clinical Practice Research Datalink (CPRD), and (3) the IQVIA Disease Analyzer (Germany). The results from the RWD show that very few pediatric patients met the clinical diagnosis of GiOP, irrespective of the database used. In sum, approximately 1 eligible subject per 1,000,000 people per year was estimated to be available for Study 20140444. The results suggest a lack of feasibility of conducting an adequate and well-controlled randomized trial in a population of pediatric patients with GiOP. The results also called into question the feasibility of other types of clinical trial designs, including potential single-arm or hybrid study designs, to fulfill the regulatory requirements. Recommendations include considering the use of RWD-based epidemiological analyses prior to agreeing with health authorities to conduct postmarketing required pediatric studies or studies in other rare diseases. This approach to clinical trial feasibility using RWD helps ensure research goals are balanced with the needs of the individual patient, further ensuring the ethical conduct of clinical trials. CLINICAL TRIAL REGISTRATION (STUDY 20140444): ClinicalTrials.gov / NCT03164928 / URL: https://clinicaltrials.gov/search? term=NCT03164928 . EudraCT / 2016-003083-39 / URL: https://www.clinicaltrialsregister.eu/ctr-search/search? query=2016-003083-39 .

Prostate cancer (PCa) is the second leading cause of cancer-related deaths among American men. Striking disparities persist in PCa incidence and mortality, with African American (AA) men experiencing a 1.7-fold higher incidence and more than two-fold higher mortality rate compared to European American (EA) men. Despite this disparity, the Black community remains underrepresented in PCa research and clinical trials. As PCa progresses to high-grade and metastatic castration-resistant stages, treatment options become increasingly limited and median overall survival falls below two years, underscoring the urgent need for novel therapeutic strategies. One promising yet underexplored avenue is the circulatory microenvironment, which consists of platelets (PLTs) and immune cells that interact directly with circulating tumor cells (CTCs) during intravasation. Mounting evidence supports a bidirectional relationship in which tumor cells activate platelets to promote thrombosis, and platelets in turn activate tumor cells to promote tumorigenesis. In PCa, reciprocal signaling between tumor cells and platelets is increasingly being recognized. Recent transcriptomic profiling (RNA-Seq) has identified transmembrane signaling proteins mediating these interactions, broadly categorized into four groups: (1) integrin-ligand, (2) EPH receptor-ephrin, (3) immune checkpoint receptor-ligand, and (4) miscellaneous receptor-ligand interactions. Notably, many components of these signaling axes are overexpressed in platelets and/or PCa cells from individuals of African ancestry and are associated with poorer clinical outcomes. These findings highlight platelet-mediated signaling pathways as a source of novel biomarkers and pharmacologically actionable targets, offering opportunities to address both aggressive disease biology and persistent PCa disparities.

The purpose of this study was to evaluate the effects of a clinician-implemented video-enhanced activity schedule and an embedded Premack contingency on on-task behavior, independent task completion, and challenging behavior for preschool-aged children with ASD. Participants included four preschool-aged children with ASD and four registered behavior technicians in one clinic. The study utilized a concurrent multiple baseline across participants design to evaluate the effects of the video-enhanced activity schedule on child on-task behavior, independence, and challenging behavior. Results indicated a functional relation between the implementation of the intervention and an increase in on-task behavior and independence; however, the results suggest a functional relation was inconclusive for reductions of challenging behavior. Social validity results indicated that participants perceived the intervention to be socially valid for instructional contexts. Study findings suggest that video-enhanced activity schedules may be an effective instructional modification for increasing on-task behavior and independence for young children with ASD. Implications for future research and practice are discussed.

In this research, we have utilized similarity analysis, synthetic accessibility assessment, and fragment design strategies to examine fluorescent chromophores. An experimental database of optical properties containing greater than 7,000 unique chromophores was utilized to assess the distribution of compounds with high photoluminescence quantum yield (PLQY). The SYnthetic Bayesian Accessibility (SYBA) scoring system was utilized to determine compounds with high fluorescence efficiencies and synthetic accessibility. Three representative compounds of high PLQY (H6, H7, H10) were utilized as standards and compared to the Harvard Organic Photovoltaic Database (HOPV15), demonstrating their structural uniqueness compared to a wide range of organic compounds. Chemical network analysis of the compounds demonstrated diversity in the structure of the compounds and their relation to fluorescence efficiencies. Fragment design using the BRICS algorithm generated greater than 2,600 compounds, some of which exhibited high structural similarity to high-efficiency fluorescent compounds and high synthetic accessibility scores.

Prophylactic dressings for pressure injury (PI) prevention have been investigated in a range of hospital settings, but there is limited evidence supporting their use in long-term acute care (LTAC) hospitals. To evaluate patient and nurse perceptions of incorporating a bordered silicone superabsorbent polymer (SAP) dressing into an LTAC PI prevention protocol. This pilot study included 50 adult patients at risk for sacral PIs, with intervention and data collection occurring between January 2024 and April 2025. Dressings were applied to the sacrum, with assessments at least daily and dressing changes no less than every 7 days. Patient- and nurse-reported outcomes (primary outcomes) included comfort, satisfaction, and usability indices. Secondary outcomes included PI incidence, adverse events, and dressing utilization. The median follow-up was 15 days, with a median of 6 dressings used per patient. Patients reported minimal discomfort, and approximately 90% rated comfort and satisfaction as good-to-excellent. Nursing staff also reported high usability. No PIs or device-related serious adverse events occurred. The bordered silicone SAP dressing was well-tolerated by patients and nursing staff within an LTAC PI prevention protocol. These findings support its consideration for integration into prevention protocols. Further research is needed to evaluate comparative PI reduction and adverse events.

Research focused on studying Hippo signaling up- and downregulation in a model of mouse lung cell regeneration. The cell-specific role of the activation and inhibition of Hippo signaling is demonstrated at the cellular level within the context of a unified bronchoalveolar lung organoid model. We used pharmacological modulators of Hippo pathway components-TRULI and verteporfin. The findings revealed that inhibition of Lats1/2 kinases via TRULI leads to different levels of Hippo gene expression for different lung cell types. The inhibition of Lats1/2 kinases enhances cell proliferation in the bronchiolar epithelium, while verteporfin suppresses it. However, no changes in the cellular composition of the bronchiolar epithelium (except ciliated cells) were observed with either TRULI or verteporfin. Inhibition of Lats1/2 kinases in the alveolar epithelium leads to a decrease in type 2 alveolocytes and alters their differentiation trajectories. The results demonstrate a cell-specific influence of Hippo modulation on the lung cells and may prove useful for the development of novel therapeutic approaches for the treatment of respiratory pathologies.

The Rating-of-Fatigue (ROF) scale is increasingly used to quantify subjective sensations of fatigue in exercise science. However, despite its growing international use, its psychometric properties have not yet been examined in Arabic-speaking populations. This study aimed to translate the ROF into Arabic and evaluate its content validity, face validity, and construct validity relative to perceived exertion and heart rate (HR) responses during graded exercise and subsequent passive recovery. The study was conducted in Tunisia and followed established international best-practice guidelines for cross-cultural adaptation. The ROF and its instructions were forward-translated, synthesized, and back-translated using blinded translators, with linguistic and conceptual equivalence evaluated using Sperber's framework and expert committee review. Face validity was assessed in 68 Arabic-speaking adults. Construct validity was examined in 43 adult participants during a modified Bruce treadmill test followed by 10&#xa0;min of seated recovery, with the Arabic Rating-of-Fatigue scale (ROF-Ar), Borg CR10, and HR recorded at each exercise stage and during recovery. Within-participant correlations were pooled using Fisher's r-to-z transformation. Sperber-based ratings indicated high linguistic and conceptual equivalence between the ROF-Ar and the original scale, with no item exceeding the predefined revision threshold. Face validity findings showed that participants predominantly interpreted the ROF-Ar as a measure of fatigue rather than exertion and that standardized instructions improved descriptor-related comprehensibility and reduced perceived difficulty. During graded exercise, ROF-Ar demonstrated very strong pooled correlations with Borg CR10 (r&#x2009;=&#x2009;0.94; 95% CI 0.92-0.95; p&#x2009;<&#x2009;0.001) and HR (r&#x2009;=&#x2009;0.95; 95% CI 0.93-0.96; p&#x2009;<&#x2009;0.001). During recovery, the association between ROF-Ar and Borg CR10 attenuated substantially (r&#x2009;=&#x2009;0.35; 95% CI 0.15-0.52; p&#x2009;<&#x2009;0.001), whereas the association with HR remained moderate (r&#x2009;=&#x2009;0.63; 95% CI 0.49-0.74; p&#x2009;<&#x2009;0.001). The Arabic version of the ROF demonstrated high linguistic and conceptual equivalence, adequate face validity, and strong construct validity. The recovery-phase dissociation between perceived fatigue and perceived exertion supports the intended conceptual distinction of the ROF and justifies the use of ROF-Ar for assessing subjective fatigue during exercise and recovery in Arabic-speaking research and applied settings.

In this study, we examined the effectiveness of Theory of Mind (ToM) intervention programs on the ToM skills of individuals with Autism Spectrum Disorder (ASD) through a systematic review and meta-analysis. A comprehensive search was conducted in Web of Science, Scopus, EBSCO ERIC, Academic Search Complete, PubMed, ProQuest, and the T&#xfc;rkiye Council of Higher Education Thesis Center, completed on January 5, 2024. Studies were included if published in English or Turkish, involved participants with ASD, implemented interventions targeting ToM, used at least one ToM assessment tool, employed a randomized controlled trial (RCT) or quasi-experimental design, and provided sufficient data for meta-analysis. Methodological quality was evaluated using What Works Clearinghouse (WWC) standards. The meta-analysis used a fixed-effects model with Hedges' g in Comprehensive Meta-Analysis Software 4. We identified 20 studies (n&#x2009;=&#x2009;924) meeting the inclusion criteria, of which 15 were included in the meta-analysis. Most interventions targeted understanding first- and second-order false beliefs and frequently used role-play and picture-based storytelling techniques. The results indicated a moderate positive effect (g&#x2009;=&#x2009;0.492, 95% CI [0.322, 0.662]). Subgroup analyses showed no significant differences based on study characteristics. Findings should be interpreted cautiously due to publication bias, small sample sizes, and the lack of IQ, language, or prerequisite skill assessments. Crucially, insufficient reporting of social validity and generalization represents a major barrier to assessing real-world utility. Future research must prioritize rigorous RCTs and systematic functional reporting to strengthen the evidence base.

Interacting disturbances involving wildfire, drought, heat extremes, insect outbreaks and wind events are increasingly reshaping ecosystem structure, regeneration and biodiversity. This review synthesises evidence on how climate change alters disturbance regimes, how wildfire interacts with other natural disturbances, and which management responses are most likely to sustain ecosystem resilience. Literature was retrieved from major academic databases and search platforms, screened using explicit eligibility criteria, and synthesised narratively. The review was guided by the Scale for the Assessment of Narrative Review Articles (SANRA). Thirty-seven (37) core studies formed the principal evidence base, supplemented by recent comparative literature used to strengthen interpretation. Across biomes, wildfire-drought interactions emerged as the most consistently documented pathway of resilience decline, commonly reducing regeneration, accelerating vegetation stress and shifting community composition. Interactions with windthrow and insect outbreaks also amplified structural damage and altered fuel conditions, although their effects depended strongly on disturbance sequence, timing and severity. Recent work on megafires, prescribed burning and fire-flammability feedbacks further shows that management cannot rely on single-disturbance assumptions. Instead, resilience depends on maintaining structural and compositional diversity, anticipating cascading effects, and aligning interventions with future climate trajectories. Overall, interacting disturbances research indicates that climate adaptation must move beyond suppression-focused strategies toward context-specific, ecologically informed management.

Metallic atrial septal defect (ASD) occluders are associated with various mid- to long-term complications. To address this, our team developed a novel biodegradable Pansy ASD occluder, and this multicenter RCT aimed to evaluate its effectiveness and safety. A prospective, multicenter, randomized controlled trial was carried out on adult and pediatric patients using the Pansy occluder with a biodegradable polydioxanone (PDO) framework. The primary efficacy endpoint of this clinical trial is the closure success rate at six months post-operation. From May 2021 to March 2023, a total of 127 patients were screened across seven research centers, with 112 patients (including 71 pediatric patients; 57 to the experimental group, 55 to the metal occluder control group) ultimately underwent occluder implantation. In these patients, the average defect size was 8.48&#x2009;&#xb1;&#x2009;2.86&#xa0;mm in the experimental group and 10.41&#x2009;&#xb1;&#x2009;5.21&#xa0;mm in the control group. The closure success rate at six months post-operation was 100% for both groups, and no residual shunt greater than 5&#xa0;mm was detected at any follow-up time point. In the experimental group, one patient required device explantation at 10 months postoperatively due to abnormal tissue hyperplasia. Pathological analysis confirmed near-complete degradation of the PDO framework with smooth endothelial coverage. A total of 109 patients completed the 12-month post-operative follow-up, with both groups again demonstrating a closure success rate of 100%. The Pansy occluder shows promising safety and efficacy outcomes at 12 months, though longer-term data are needed to confirm durability.

Cephaeline (CPL), a bioactive compound derived from the medicinal plant Ipecacuanha, has demonstrated inhibitory effects on several tumor types. Nevertheless, its role in breast cancer and the underlying molecular mechanisms remain largely unexplored. This research aimed to investigate the anti-cancer potential of CPL in breast cancer cells. The IC50 of CPL was determined using the CCK-8 assay. Subsequently, the effects of CPL on cell migration and proliferation were assessed through wound healing (scratch) and colony formation assays, respectively. Additionally, MDA and GSH levels were quantified using ELISA, while ROS production was visualized via DHE staining. Intracellular iron content was measured using an iron assay kit. Furthermore, the expression levels of p53, SLC7A11, and GPX4 were evaluated using Western blot. All experiments were performed in triplicate and independently repeated at least three times, and data were analyzed using Student's t-test or one-way ANOVA, as appropriate. CPL significantly inhibited the proliferation and viability of 4T1 and MDA-MB-231 breast cancer cells in a dose-dependent manner, with IC50 values of 38.89&#xa0;nM and 50.29&#xa0;nM, respectively, and concomitantly suppressed cell migration and colony formation at higher concentrations. It also increased intracellular MDA and ROS and downregulated GSH, SLC7A11 and GPX4, inducing ferroptosis. siRNA knockdown of p53 attenuated CPL's effects, indicating p53's key role in CPL's anti-cancer activity. This study provides evidence that CPL exerts anti-breast cancer effects by promoting ferroptosis through the p53/SLC7A11/GPX4 axis, highlighting its therapeutic potential as a novel agent for cancer treatment.

Early-career academics (ECAs) constitute a substantial part of the teaching workforce in health professions education (HPE), yet their teacher identity is often marginalized in academic and clinical workplaces and may therefore remain underdeveloped. This study investigates how ECAs, with teaching responsibilities in HPE, construct and negotiate their teacher identities in relation to valuing teaching. Qualitative data from 11 ECAs across three Danish research-intensive universities were collected through semester-long audio diaries and exit interviews. Teacher identity was theorized using Kelchtermans' (2009) Personal Interpretative Framework as a sensitizing concept for understanding what it means to be a teacher, while Dialogical Self Theory (Hermans, 2001) was used to analyze the findings with attention to the dynamic processes of identity formation. Key findings showed that ECAs' teacher identity constructions and negotiations were shaped by tensions between internalized institutional priorities that often devalue teaching, a lack of community and support that can lead to loneliness, and their own personal motivation and moral commitment to teaching. The study contributes two constructs central to explaining this: (1) institutionally imposed template identities to not prioritize teaching, and (2) loneliness related to imagined teacher communities. The study recommends supporting teacher identity through recognition of teaching as a relational and moral practice. Faculty development should address loneliness, and institutions should avoid exploiting ECAs' altruism and ensure that institutional recognition of teaching holds real weight in reward and career systems.

Community-academic partnerships are increasingly recognized as essential for advancing equitable public health outcomes. Yet many partnerships struggle to move beyond short-term, project-based collaboration toward sustained, trust-based engagement with communities. This commentary draws on the experience of the University of California San Diego Center for Community Health (CCH) and its long-standing partnerships with immigrant, refugee, and other underserved communities in San Diego County. Over more than two decades of practice, CCH and its community partners developed the Community-Led Transformation (CLT) approach to guide authentic community-academic collaboration. We describe three interdependent pillars of CLT: valuing community expertise, fostering trust-based partnerships, and ensuring fair access to resources and power-sharing. Examples from CCH programs, coalitions, and research collaborations illustrate how these principles are operationalized in practice. We also reflect on structural challenges within academic institutions, including funding instability, administrative barriers, and limitations in partnership infrastructure, and strategies used to navigate these constraints while sustaining community partnerships. We provide specific recommendations for academic partners, community partners, and funders to facilitate community-academic partnerships via increased capacity building, infrastructural supports, and greater relationship and trust building. The CLT framework has therefore been a success within CCH, and can provide practical insights for a variety of partners and institutions seeking to build authentic, durable partnerships that meaningfully advance public health and health equity.

Alzheimer's disease (AD) is the most common form of dementia, driven by complex interactions among aging-related biological changes, neuronal degeneration, mitochondrial dysfunction, and environmental factors. Despite extensive research, effective disease-modifying therapies remain unavailable. Increasing evidence highlights the gut-brain axis as an important contributor to AD pathogenesis, particularly through amyloid-producing gut microbes that promote immune activation, neuroinflammation, and cerebral amyloid accumulation. This review summarizes current evidence linking gut microbiota (GM) dysbiosis to AD, focusing on microbial metabolites, neuroinflammatory pathways, and microbiota-targeted therapeutic strategies. A systematic analysis of experimental and clinical studies reveals that altered gut microbial composition is associated with systemic and neuroinflammation, blood-brain barrier dysfunction, oxidative stress, and neuronal damage. Key microbial metabolites, including short-chain fatty acids and indole derivatives, exhibit neuroprotective effects by regulating immune responses, maintaining barrier integrity, and supporting neuronal energy metabolism; disruption of these metabolites may accelerate neurodegeneration. Microbiota-based interventions such as probiotics, prebiotics, dietary modification, and fecal microbiota transplantation show beneficial effects in preclinical models by restoring microbial balance and reducing neuropathological features, although clinical evidence in humans remains limited. Overall, current findings support a contributory role of gut dysbiosis in AD and suggest that targeting the GM may offer a promising complementary strategy for disease modification and future therapeutic development.

C.H. Waddington (1905-1975) was a British biologist and perhaps the major figure in developmental biology between the 1940s and 1960s. He is one of the few pre-molecular-age developmental biologists still widely remembered. This is for his pioneering work on using mutations to probe embryogenesis, for his deep analysis of how gene activity drives developmental change (summarised in his illustration of the epigenetic landscape), for his exploration of the mechanics of evolutionary change in the developing phenotype and for his terminology, much of which remains in common usage. Waddington died some 50&#x2005;years ago, and this short article examines some of his key research papers that underpin these achievements and still remain significant. The supplementary material, available online, includes songs composed for Waddington's 50th birthday.