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Inadequate supply of oxygen causing hypoxic cellular stress drives metabolic reprograming across diverse physiological conditions, including cancer. The activation of hypoxia-inducible factors (HIFs) to facilitate adaptation to low oxygen environments is well-characterized; however, post-transcriptional regulation by microRNAs (miRNAs) is poorly understood. Here, we investigated the mRNA and miRNA response in hypoxia-mediating reduced growth and cellular metabolism. Next-generation sequencing revealed the impact of hypoxia in cultured human hepatocellular carcinoma cells and identified over 400 mRNAs and 140 miRNAs that were differentially expressed. Hypoxia upregulated mRNA transcripts associated with glycolysis, DNA replication and the PI3K (phosphoinositide 3-kinase)-Akt pathway, which promote anaerobic metabolism for energy production, decreased cell proliferation and genomic instability, respectively. Upregulated miRNAs included miR-197-3p and miR-766-3p, targeting genes involved in lipid biosynthesis and metabolism. Downregulated miRNAs included miR-33a-5p and miR-15a-5p, targeting genes involved in glycolysis and lactate metabolism. Notably, miR-6834 emerged as a potential regulator of mechanistic target of rapamycin (mTOR) signaling and insulin-like growth factor binding protein-1 (IGFBP-1) signaling; miR-6834 overexpression altered 4E-BP1 phosphorylation levels and IGFBP-1 secretion. These findings provide critical insights into miRNA-mRNA regulation of metabolic adaptation and highlight miRNAs as potential targets for interventions with relevance to tumor biology and other hypoxia-associated conditions.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the buildup of aggregated amyloid-beta (Aβ) peptides. We previously demonstrated that Aβ is produced from APP following its lysosomal internalization via macropinocytosis. However, the regulation of APP macropinocytosis in neuronal cells remained uncharacterized. Arf6 and the Rho GTPases Rac1, Cdc42 and RhoA are known to regulate macropinocytosis in response to signaling at the cell surface. Fe65, an adaptor protein known to interact with APP, may link APP to these regulatory elements. We hypothesized that APP binding/crosslinking recruits Fe65, which recruits/activates Arf6 and then Rac1, Cdc42, and RhoA, driving APP macropinocytosis. We found that antibody-mediated binding/crosslinking APP resulted in the transient recruitment of Fe65 and Arf6 to APP within 30 s of APP binding/crosslinking. Rac1, Cdc42, and RhoA were also recruited at 30 s, but remained recruited through 2 min. The mutation of the APP 'YENPTY' sequence and Arf6 inhibition by NAV-2729 prevented the recruitment of Rac1, Cdc42, and RhoA. Together, these observations are the first to demonstrate that a network of regulatory proteins is recruited to bound/crosslinked APP and regulates its macropinocytosis. Targeting these regulatory proteins to modulate APP trafficking to the lysosome could be a therapeutic strategy to reduce Aβ production in AD.

Clinical guidelines suggest body mass index (BMI) thresholds of ≥25 kg/m² to identify individuals at elevated risk of type 2 diabetes and (T2D) hypertension, however, growing evidence suggests that higher BMI values within the normal weight range may also be associated with increased risks. A systematic search was conducted in PubMed and Scopus, with an updated PubMed search through October 2025, to identify cohort studies from the US and Europe that reported risk estimates of T2D or hypertension for higher normal weight BMI values (e.g., 22.5-24.9 kg/m²) compared with lower normal weight BMI values. Asian studies were excluded because of lower BMI thresholds in Asian populations. Random-effects meta-analysis was performed to estimate summary relative risks (RRs) and 95%CIs. Eleven cohort studies were included, with 23% of participants and 17% of cases being classified as having high normal weight BMI values (22.5-24.9 kg/m²). Compared with lower BMI values within the normal weight range, high normal weight BMI values were associated with a greater risk of T2D (RR = 1.78, 95% CI: 1.30-2.45, I² = 98%; n = 10 studies with 1,818,036 participants and 84,414 cases; moderate certainty evidence). Evidence for hypertension was limited, based on three US cohort studies (RR = 1.42, 95% CI: 1.33-1.51, I2 = 0; n = 3 studies with 129,046 participants and 22,254 cases; low certainty evidence). Compared with lower normal weight BMI values, higher BMI within the normal range was associated with a higher risk of T2D and hypertension, suggesting that current BMI classifications may not fully capture the increased risk among individuals at the upper end of the normal weight spectrum. If replicated, the findings may justify reconsideration of BMI thresholds to better reflect the higher cardiometabolic risk observed among individuals with high normal weight BMI.

Sequential transplant research is the administration of distinct study interventions in sequential phases (donor, organ, recipient) of the same organ transplant. This guideline provides a framework for assessing the suitability of implementing ≥2 transplant studies sequentially. We applied World Health Organization guideline methodology. The guideline panel included transplant researchers, transplant patients and organ donor family members, randomized trial methodologists and biostatisticians, and research ethics scholars. Three principal themes included the impact of sequential research on patient safety, study findings, and strategies for effective implementation. The panel met on 7 occasions during 4 mo. Patient safety indicates that sequential studies have potential to harm transplant recipients in 3 situations: when investigational drugs are the same in both studies, they have a classic drug-drug interaction, or they have similar adverse effects. Study findings indicates that sequential research might influence study estimates of relative risk only if 1 intervention modifies (ie, amplifies or suppresses) the effects of another. In contrast, with or without effect modification, sequential research can influence the power of a study to detect expected treatment effects. An appreciable impact on study power will only arise, however, when there is a high rate of sequential enrollment in the study population. Implementation indicates that ideally, to maximize research efficiency, independent bodies will judge the suitability of sequential research, and research organizations will develop an equitable approach to support studies found unsuitable for sequential implementation. This guideline represents a starting point to advance the safe implementation of sequential trials in transplantation.

Tumor-associated macrophages are key components of the tumor microenvironment in oral carcinogenesis; however, their role is not yet fully understood. We aimed to characterize the expression of macrophage (M) markers across the spectrum of oral carcinogenesis, including oral leukoplakias (OL) and oral squamous cell carcinomas (OSCCs). This immunohistochemical study analyzed the macrophage density (cells/mm2) based on the expression of CD68 (pan-macrophage), CD163 (M2), and CD80 (M1) in 81 samples, including healthy mucosa (n = 16), OL (n = 30), and OSCC (n = 35), in both epithelial and subepithelial compartments. All markers showed a progressive increase across the study groups, with significantly higher densities in OSCC than in healthy mucosa (p < 0.001), consistently higher in the subepithelial compartment. CD163 was the most expressed marker (increasing from 78.96 cells/mm2 in healthy mucosa to 300.56 cells/mm2 in OSCC), whereas CD80 was the least abundant, particularly in OSCC (35.66 cells/mm2 in healthy tissue to 188.49 cells/mm2 in OSCC). No significant associations were observed between biomarker expression and clinicopathological variables. These results support the involvement of macrophages during oral carcinogenesis, particularly CD163+ (M2) cells, and highlight the potential prognostic and therapeutic relevance of these markers.

Recurrent pregnancy loss (RPL) continues to be a significant challenge in reproductive medicine, particularly in women for whom standard examinations do not reveal a conclusive underlying reason. There is growing evidence that several instances may result from nuanced alterations in the endometrial milieu, particularly with decidualization and maternal-fetal immune tolerance. In recent years, vitamin D has gained recognition for its significance in early pregnancy, serving not only as a regulator of calcium metabolism but also as an active contributor to endometrial and immunological functions. The human endometrium exhibits the vitamin D receptor (VDR) and the enzyme CYP27B1, facilitating the local activation and signaling of vitamin D inside the uterine milieu. Experimental investigations have shown that vitamin D influences many processes critical for effective implantation and placentation, including stromal cell differentiation, cytokine equilibrium, trophoblast invasion, oxidative stress responses, and immune cell communication. Aberrant vitamin D signaling has been associated with heightened inflammatory activity, impaired decidual transformation, altered uterine natural killer cell functionality, and alteration of the Treg/Th17 equilibrium, all of which have been implicated in recurrent pregnancy loss. Concurrently, there is an increasing emphasis on the association between vitamin D and mitochondrial function as well as oxidative stress in decidual and endometrial cells. Interruption of these pathways may influence implantation and early embryonic development by impacting cellular metabolism and immunological control at the maternal-fetal interface. The clinical interest in vitamin D supplementation for women experiencing repeated reproductive failure is increasing; nevertheless, the existing results are conflicting, mostly due to the predominance of research focusing on circulating vitamin D levels rather than localized tissue-specific processes. Our review encapsulates new findings about the function of vitamin D in endometrial biology and reproductive immune regulation, emphasizing its involvement in decidualization, inflammatory signaling, oxidative stress, and maternal-fetal immunological tolerance in recurrent pregnancy loss. The potential ramifications for assisted reproduction and forthcoming tailored therapy techniques are also examined.

To date, evidence suggesting the optimal timing of antibody testing in human T-cell lymphotropic virus type 1 (HTLV-1)-exposed infants is lacking. Testing HTLV-1-exposed infants must balance the need for repeat testing if done too early while minimizing loss to follow-up with protracted follow-up intervals. Single-center, retrospective cohort analysis of HTLV-1 serologic testing and breastfeeding practices in infants born to HTLV-1 seropositive pregnant individuals between 01/01/2016 and 10/03/2026. Nineteen children were identified, of whom 5 had positive serological tests for HTLV-1 when first tested, and 14 were seronegative on the first sample, with a median age at first negative test of 18.4 months (95% confidence interval: 6.9). None have been confirmed infected. Six children were known to have breast/chest-fed for an average of 4.5 months. Serologic testing of HTLV-1-exposed infants can be done at 18 months, minimizing persistent transplacental positives and follow-up attrition.

Background/Objectives: To examine adherence to the specific goals of the nutrition component of a healthy lifestyle intervention program during pregnancy (the Nutrition and Exercise Lifestyle Intervention Program; NELIP) from baseline at 12-18 weeks gestation to trial midpoint (24-25 weeks gestation) and endpoint (34-36 weeks gestation). Methods: A convenience sample of 90 individuals were included in the secondary analysis. Participants completed the pregnancy intervention in one of three groups: NE, nutrition and exercise introduced simultaneously; N+E, nutrition introduced first followed by exercise introduced at midpoint; or E+N, exercise introduced first followed by nutrition introduced at midpoint. A meal plan with guidelines for carbohydrate and protein consumption was included in the nutrition component, and adherence to the specific meal plan goals was tracked using a novel rubric developed especially for the meal plan in the NELIP intervention. Results: All groups had improvements in nutrition adherence from baseline to midpoint, with the NE group scoring highest in adherence (12.9 &#xb1; 2.0 points) at midpoint compared to the N+E (11.2 &#xb1; 1.8 points) and E+N (11.8 &#xb1; 2.0 points) groups (F(2, 85) = 6.08, p = 0.00, &#x3b7;2 = 0.13). From midpoint to endpoint, N+E was the only group with no decline in adherence. Conclusions: The N+E group had the most stable improvements in adherence over the course of the intervention, despite better improvements in adherence from baseline to midpoint in groups NE and E+N. Time of intervention component introduction may have a differential impact on adherence score fluctuation, with baseline nutrition scores potentially influencing nutrition habits over time.

Peripheral neuropathy (PN) is one of the most common disorders of the peripheral nervous system, affecting around 10% of the general adult population. PN results in pain, paraesthesia, and sensory loss, negatively impacting patients' quality of life. The condition is characterised by damage to peripheral nerves and is often linked to risk factors, among which diabetes is the most common cause. The incidence rate of patients suffering from PN has significantly increased in the last three decades, yet there are currently no pharmacological treatments to reverse or prevent the development of PN. Therefore, neurotropic B vitamins, specifically vitamins B1, B6, and B12, which are essential for protecting nerves from damage, nerve regeneration, and maintaining nerve health, are promising treatment options. Other biofactors with therapeutic potential are vitamin D3, which has been described as a regulator of neuroplasticity and neuroinflammation with indications to promote neuronal regeneration following injury, as well as alpha-lipoic acid (ALA), a well-described treatment option in PN. The regenerative capacity of vitamins B1, B6, B12, and D3 and ALA was determined following neurite degeneration in vitro induced by either hydrogen peroxide (H2O2) or homocysteine. In line with previous studies, the results show that a combination of vitamins B1, B6, and B12 has a significantly better effect on neurite extension following homocysteine-induced degeneration. In H2O2-insulted neural cells, the combination of all three neurotropic B vitamins was also shown to be superior to that of individual B vitamin treatment, demonstrated by longer neurite length after insult. Vitamin D3 also demonstrated a neuro-regenerative effect on neurites in healthy and insulted neural cells, whereas ALA only appears to provide a protective effect, preventing ongoing damage and supporting neurite outgrowth in healthy cells. No synergistic effects were seen with any treatment combinations. We have established an in vitro model of homocysteine-induced degeneration, and using this model alongside H2O2-induced degeneration, we provide evidence of the neurite regenerative capacity of vitamins B1, B6, B12, and D3.

Nickel-based cathodes are widely used in alkaline water electrolysis, yet the nature and stability of the active surface under operating conditions remains unclear. In particular, the role of metal/oxo-hydroxo interfacial structures in governing hydrogen evolution activity is not well understood. Here, we employ a multimodal, depth-sensitive approach combining operando Ni L-edge X-ray absorption spectroscopy, depth-sensitive X-ray absorption measurements in total electron yield and Auger electron yield modes, X-ray photoelectron spectroscopy, isotopically labeled nano secondary ion mass spectrometry, and online electrochemical mass spectrometry to directly track the evolution of Ni/NiOxHy interfaces during the hydrogen evolution reaction. Using well-defined sputtered Ni thin films as a model system, we show that progressive reduction of near-surface oxide/hydroxide species is accompanied by a gradual loss of hydrogen evolution activity. Depth-resolved measurements reveal a predominantly metallic outermost surface under cathodic bias, while NiOxHy forms on the surface upon relaxation to open-circuit conditions. Importantly, mild anodic pre-conditioning regenerates subsurface NiOxHy species, resulting in a sustained increase in hydrogen evolution activity upon subsequent cathodic polarization. These results establish the crucial role of metal/oxo-hydroxo interfaces as active phases for hydrogen evolution and provide a framework for engineering robust, Earth-abundant HER cathodes capable of operating under dynamic, real-world electrolysis conditions.

Background/Objectives: The levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used as a long-acting reversible contraceptive and as a therapeutic option for heavy menstrual bleeding, endometriosis, adenomyosis, and endometrial hyperplasia. Although its predominant effect is local, systemic levonorgestrel exposure has raised questions regarding its potential influence on cancer risk. This review aims to summarise and critically appraise the available evidence on the association between LNG-IUD use and gynaecologic, breast, and selected non-gynaecologic malignancies (including colorectal, lung, pancreatic, gastric, thyroid, skin [melanoma], and haematological cancers). Methods: A structured narrative review was developed by a multidisciplinary expert group affiliated with the European Society of Gynaecological Oncology (ESGO) and the European Society for Gynaecological Endoscopy (ESGE). PubMed/MEDLINE, Embase, and Scopus were searched in December 2024 without publication-date restrictions. We critically appraised epidemiological and clinical evidence on LNG-IUD use and breast, endometrial, ovarian, cervical, and selected non-gynaecologic cancer risks, prioritising population-based cohorts, registry-based studies, case-control studies, systematic reviews, and meta-analyses. Results: The strongest and most consistent evidence supports a substantial reduction in endometrial cancer risk among LNG-IUD users, with a possible protective association also suggested for ovarian cancer. Available data do not indicate a clear increase in cervical cancer, CIN3+, or invasive cervical disease. In contrast, evidence for breast cancer remains heterogeneous, with some registry-based studies suggesting a modest relative increase and other cohort or case-control studies showing no significant association. Evidence regarding non-gynaecologic cancers remains limited and inconclusive. Conclusions: Overall, current evidence suggests that the LNG-IUD has a favourable oncological safety profile, with the strongest evidence supporting a significant reduction in endometrial cancer risk and a potential protective effect against ovarian cancer. There is no evidence pointing to increased risk of cervical cancer. However, results related to breast cancer are mixed, and a slight risk increase cannot be ruled out; thus, counselling should be personalised based on the indication, menopausal status, duration of use, and individual breast cancer risk.

Constraint-based modeling is a well-established modeling methodology used to study biological networks at both the medium-scale and genome-scale. Due to their large size and complexity, such steady-state flux models are typically analyzed using constraint-based optimization techniques, such as Flux Balance Analysis (FBA). The Flux Balance Constraints (FBC) Package extends SBML Level 3 to provide a standardized format for encoding, exchanging, and annotating constraint-based models. It includes support for modeling concepts such as objective functions, flux bounds, and annotation of model components that facilitate reaction balancing. Version two extended the original release by adding support for encoding gene-protein associations. Version three builds upon and maintains backwards compatibility with Version two by introducing new elements and attributes that include: user-defined constraints, a new quadratic variable type and key-value pair annotation that can be used to store additional information relevant to constraint-based modeling. The only changes to existing attributes are that a Species charge is no longer restricted to an integer value and chemicalFormula can now include generic components. In addition to providing the elements necessary to uniquely encode constraint-based models, the FBC package provides an open platform that facilitates the continued, cross-community development of an interoperable, constraint-based model encoding format.

Background/Objectives: Acupuncture is effective for labor pain yet rarely used in the UK. Midwife-delivered acupuncture (commonplace in Europe) is cost-effective but typically demands a protocol-based approach. Randomized controlled trial (RCT) protocols have varied greatly in terms of acupuncture rationale/style, needle number/location and retention time. The aim of this study was to determine the intrapartum acupuncture experience of professional UK acupuncturists specializing in pregnancy/childbirth and compare their treatment recommendations with research evidence regarding acupuncture "dose" during labor. Methods: Fifty self-identified obstetric acupuncturists (various styles) with 10 [4, 6] years of experience (median [interquartile range]) were surveyed about their personal intrapartum acupuncture experience and recommendations regarding traditional acupuncture point selection and overall treatment approach. Results: Of 50 respondents, 36% (n = 18) had never attended a labor. For those with experience, the median number of labors attended was 0.4/year [interquartile range 0.1-0.3]. Only 12% (n = 6) had attended &#x2265;10 labors. Recommendations included using between 2 [1, 2] and 8 &#xb1; 4 (mean &#xb1; standard deviation) needles left in situ for 5 [1, 10] to 30 [30, 30] min. Only 32% (n = 16) advised retention throughout labor, of which 25% (n = 4) would tape needles down. The remainder advised interval treatments, typically 1-2 hourly. Most practitioners highlighted the need to vary the treatment according to individual needs/sensitivity. Regarding points, only SP6 and LI4 were ubiquitous, although 41/51 RCT points were mentioned, which were most often segmental and/or so-called major points for central effects (SP6/LI4/BL32/BL60/LR3/BL67/PC6/BL31/ST36/Shenmen). Regarding needle stimulation, 18% (n = 9) recommended none, 20% (n = 10) elicitation of de qi only, and 54% (n = 27) repetitive manual manipulation (every 5-15 min). Only 8% endorsed electroacupuncture use. Conclusions: UK experience with intrapartum acupuncture appears limited. Most practitioners recommended short periods of needling using relatively few needles, i.e., low-dose acupuncture.

To prospectively compare treatment outcomes for orthograde canal obturation using Ortho MTA III (OMTA) with the continuous wave of compaction (CWC) using gutta-percha (GP) and AH Plus sealer, and to identify associated predictive factors. Informed consent was obtained (110 patients), and single- or two-rooted permanent teeth (n&#x2009;=&#x2009;120) diagnosed with pulp necrosis (or previously treated) and asymptomatic apical periodontitis or chronic apical abscess (periapical index, PAI&#x2009;&#x2265;&#x2009;3) were randomly assigned to two groups (n&#x2009;=&#x2009;60/group). The canals were prepared to a minimal apical size #40 (ISO) based on their initial file size, disinfected and obturated by either CWC or OMTA using an enhanced disinfection protocol (GP disinfected, new gloves after each intraoperative radiograph and before starting obturation). Clinical and periapical radiographic examinations were conducted by two calibrated, independent endodontists during follow-up periods of at least 12&#x2009;months. Success rates and associated predictive factors (tooth-, operator- and patient-related) were analysed statistically using binary and multiple logistic regression (p&#x2009;<&#x2009;0.05). The median recall period was 30&#x2009;months (14-48&#x2009;months), and 104 teeth were finally analysed (recall rate: 86.67%). No significant differences in success rate were observed between the groups (p&#x2009;>&#x2009;0.05) under both loose (OMTA: 88.24%, CWC: 83.02%) and strict criteria (OMTA: 64.71%, CWC: 58.49%). Multivariate analysis revealed that age (OR&#x2009;=&#x2009;5.735, 95% CI: 1.286-25.577, p&#x2009;=&#x2009;0.022), periapical lesion size (OR&#x2009;=&#x2009;6.596, 95% CI: 1.397-31.138, p&#x2009;=&#x2009;0.017) and PAI score (OR&#x2009;=&#x2009;2.081, 95% CI: 1.047-4.136, p&#x2009;=&#x2009;0.036) were significant predictors of treatment failure. Orthograde obturation of infected canals with Ortho MTA III demonstrated comparable success and treatment outcomes to those filled with GP and sealer by CWC, supporting its potential as a clinically viable alternative for the obturation of infected root canals. cris.nih.go.kr registration number: KCT00099939.

In accelerometer-based measurement, the inclusion of upper extremity (UE) activity during walking can overestimate real-world functional UE use in people post-stroke. This study introduces a comprehensive, accelerometer-based approach to examining real-world UE use, including the contribution of UE activity during walking, and compares UE use during walking versus ADL-based activities. People with subacute stroke wore bilateral wrist and ankle inertial measurement units (IMU) for one week (24 h/day). Agreement between UE-Total, UE-Continuous Walking and UE-ADL measures were assessed using Bland-Altman analyses. Variables were modeled using linear regression to explore step count, mobility aid use and UE motor impairment as predictors of IMU measures of real-world UE use. Agreement between UE-Total and UE-ADL measures showed minimal bias. Differences between UE-Continuous Walking and UE-ADL varied by mobility aid. UE-Continuous Walking was associated with increased UE activity and relatively greater paretic arm use compared with UE-ADL. Across UE-Continuous Walking and UE-ADL, step count was the strongest predictor of real-world UE use. UE activity during continuous walking exhibits different use patterns as compared to ADL-based activity. Accordingly, separating continuous walking-related UE activity from ADL-based UE use may improve clinical interpretation of IMU measures of real-world UE use in individuals with subacute stroke.

Cardiovascular diseases (CVDs) remain the foremost cause of death globally, responsible for 19.2 million deaths and 437 million disability-adjusted life years in 2023, with prevalent cases having more than doubled since 1990. No approved therapy restores myocardium lost to infarction. The adult heart replaces cardiomyocytes at approximately 1% per year in young adults, declining to about 0.45% per year with ageing, far below what is needed to recover the more than one billion cells destroyed by a large myocardial infarction. Cell-based regenerative strategies have been investigated for more than two decades, encompassing bone marrow mononuclear cells (BM-MNCs), mesenchymal stromal cells (MSCs), cardiac progenitor cells, cardiosphere-derived cells (CDCs), skeletal myoblasts, and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Safety has been consistent. Efficacy has been modest and variable: the CADUCEUS trial demonstrated scar mass reduction with CDCs without proportionate ejection fraction improvement; the Phase 1/2 POSEIDON trial confirmed MSC safety in 30 patients; and the Phase 3 DREAM-HF trial, enrolling 537 patients, failed its primary endpoint (HR 1.2, p = 0.406). Mechanistic work has established that transplanted cells engraft poorly and exert their benefit principally through paracrine signalling mediated by secreted extracellular vesicles and exosomes carrying microRNAs, trophic factors, and immunomodulatory proteins. For iPSC-CMs, electrophysiological immaturity and arrhythmogenic risk in primate models remain unresolved barriers. Emerging strategies include CRISPR-engineered hypoimmune iPSC lines, bioengineered cardiac patches, injectable hydrogel scaffolds, and engineered exosome platforms. This review provides a comprehensive synthesis of preclinical and clinical evidence, examines translational barriers, and identifies the scientific and regulatory priorities required before these therapies can enter routine clinical practice.

Effective motor neurone disease (MND) management depends on patient and carer involvement in decisions about interventions and future care. Communication and cognitive impairments are common in MND and have under-recognised consequences for shared decision making and autonomy. This narrative conceptual review draws on empirical qualitative research with people living with MND and unpaid family carers and the literature specifically concerning shared decision making and communication in MND. Themes relating to communication, information use, and decision making styles were mapped onto an ALS/MND multidisciplinary decision making model. Enhancements to the model include expanding the decision making context beyond in clinical activity, embedding communication and cognitive skills and accommodations across stages, and acknowledging risks to collaborative decision making. Practical strategies for clinicians, healthcare services, people living with MND, and family carers are proposed to ensure that communication is foregrounded in-person-centred MND care. Observational and implementation research is required to evaluate and refine the proposed approaches.

Background/Objectives: Falls-prevention advice in primary care does not always lead to a practical next step. We evaluated a brief, non-clinical Falls Conversation package at one urban NHS general practice. Methods: During a 12-week quality improvement/service evaluation, patients aged 65 years or older were offered a baseline reflection survey, written information, a home-safety checklist and, in later Plan-Do-Study-Act (PDSA) cycles, a one-action prompt. The package did not include clinical assessment, treatment, referral or medication review. Matched pre-post outcomes were analysed, with actions and balancing outcomes recorded at four to six weeks. Results: Of 510 eligible patients, 442 were approached, 334 engaged, 295 provided matched pre-post data and 256 completed follow-up. The mean project-specific knowledge score was 1.83 (SD 1.02) before and 2.60 (SD 0.95) immediately after the package, a paired difference of 0.77 out of 4 (95% CI 0.65 to 0.88; Cohen's d_z = 0.79; p < 0.001). Worry changed by -0.07 out of 5 (95% CI -0.13 to -0.01; d_z = -0.13), and activity avoidance by -3.4 percentage points (95% CI -7.5 to 0.7; p = 0.144). At follow-up, 157/256 participants reported at least one action (61.3%, 95% CI 55.2% to 67.1%); actions were heterogeneous and unverified. Action selection and completion rose descriptively across non-randomised PDSA cohorts. Conclusions: The package appeared feasible to embed in one practice and was associated with higher immediate knowledge scores and patient-reported action. It did not demonstrate reduced falls or clinically meaningful change in fear-related outcomes. Controlled studies using validated measures, objective outcomes and longer follow-up are required.

Ruthenium oxide (RuO2) is the most promising alternative to iridium oxide (IrO2) catalyst in proton-exchange-membrane water electrolysis (PEMWE). However, its practical application has been hindered by poor stability. Here, we developed an interface-growth-assisted molten salt synthesis (MSS) strategy for the preparation of stable cobalt (Co)-embedded RuO2 (Co-RuO2) nanorods using a lanthanum cobaltate (LaCoO3) template. The MSS environment is beneficial for anisotropic growth and the exposure of highly active RuO2 crystal planes. Moreover, the in situ topological transformation arising from the interface growth of RuO2 on LaCoO3 can further enhance these effects and incorporate Co into the RuO2 lattice. The PEMWE electrolyzer with Co-RuO2 as the anode catalyst can operate steadily for over 300 h at 500 mA cm-2. Theoretical simulations indicate that Co substitutions would stabilize oxygen vacancies and increase metal-oxygen covalency, thereby lowering cell voltage and improving the stability of the PEMWE electrolyzer. This work pioneers template-directed interface growth in an MSS environment to prepare anisotropic RuO2 catalysts for practical PEMWE applications.