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The role of lifestyle interventions in symptom management and disease modification in Parkinson's disease
No full textEmerging evidence indicates that sustainable lifestyle changes—such as increasing physical activity, adopting healthy dietary patterns, and managing stress—can provide symptomatic benefits and potentially slow neurodegeneration in Parkinson's disease. Combining these interventions could produce synergistic effects, addressing multiple aspects of the pathophysiology. Despite the challenges of long-term adherence, innovative approaches such as digital tools and personalised strategies can support sustained lifestyle modifications. Tailoring interventions to individual needs and cultural contexts is crucial, especially in diverse socioeconomic settings. Future research should focus on large-scale, long-term studies to better understand the disease-modifying potential of lifestyle interventions and explore the biological mechanisms underlying their benefits. Overall, integrating lifestyle modifications into routine care offers a promising, accessible avenue to improve quality of life and potentially alter the progression of Parkinson's disease.</p
Defying the Landlords:Leftwing Radicalism in the Countryside, 1880-1950
No full textRurale gemeenschappen worden in populaire beeldvormingen vaak voorgesteld als conservatieve ecosystemen gehecht aan tradities en bestaande structuren. De geschiedenis van onder andere de Amerikaanse prairies en de Mississippi Delta en de Noord-Nederlandse veen- en landbouwgebieden vertellen echter een ander verhaal. Daar schoot links gedachtegoed wortel aan het eind van de negentiende eeuw
GenSwarm:Scalable Multi-Robot Code-Policy Generation and Deployment via Language Models
No full textThe development of control policies for multi-robot systems traditionally follows a complex and labor-intensive process, often lacking the flexibility to adapt to dynamic tasks. This has motivated research on methods to automatically create control policies. However, these methods require iterative processes of manually crafting and refining objective functions, thereby prolonging the development cycle. This work introduces GenSwarm, an end-to-end system that leverages large language models to automatically generate and deploy control policies for real-world multi-robot systems based on user instructions in natural language. As a multi-language-agent system, GenSwarm achieves zero-shot learning, enabling rapid adaptation to altered or unseen tasks. The white-box nature of the code policies ensures strong reproducibility and interpretability. With its scalable software and hardware architectures, GenSwarm supports efficient and automated policy deployment on both simulated and real-world multi-robot systems, realizing an instruction-to-execution end-to-end functionality that may transform the development paradigm of multi-robot systems in the future
Occurrence of Potential Prescribing Cascades After Hospital Discharge:A Cohort Study
No full textPURPOSE: A prescribing cascade (PC) occurs when a medication (index) causes an adverse drug reaction (ADR), which is addressed by prescribing additional medication (marker). Medication initiated in the hospital may cause post-discharge ADRs and PCs, especially when multiple healthcare providers are involved. The study aimed to assess the cumulative incidence of potential PCs post-discharge and identify the healthcare providers involved in prescribing the marker medication.METHODS: A cohort study was conducted among adult patients admitted in one hospital between 2019 and 2023, who initiated medication associated with preselected PCs (n = 20). A PC was defined as the initiation of a marker medication which may be intended to treat an ADR induced by the index medication. Data from the hospital and the Nationwide Medication Record System were used to identify potential PCs post-discharge. The primary outcome was the cumulative incidence of PCs, estimated for PCs with ≥ 10 patients initiating the index medication. The secondary outcome was the percentage of cases where the marker medication was prescribed by a healthcare provider outside the hospital, for PCs with ≥ 10 patients initiating the marker medication. Descriptive statistics were used.RESULTS: Among 24 282 patients initiating index medication, 502 potential PCs were observed. The cumulative incidence was estimated for 17 PCs, ranging from 0% to 12.3%. Across 12 PCs with ≥ 10 patients, percentages of marker medications prescribed outside the hospital ranged from 31.8% to 92.8%.CONCLUSION: The cumulative incidence of potential PCs post-discharge can be substantial with marker medication often initiated by healthcare providers outside the hospital.</p
Membrane-protein-mediated phase separation orchestrates organelle contact sites
No full textMitochondria and the endoplasmic reticulum (ER) contain large areas that are in close proximity. Yet the mechanism of how these inter-organellar adhesions are formed remains elusive. Tight functional connections, termed "membrane contact sites," assemble at these areas and are essential for exchanging metabolites and lipids between the organelles. Recently, the ER-resident protein PDZ domain-containing protein 8 (PDZD8) was identified as a tether between the ER and mitochondria or late endosomes/lysosomes. Here, we show that PDZD8 can undergo phase separation via its intrinsically disordered region (IDR). Endogenously labeled PDZD8 forms condensates on membranes both in vitro and in mammalian cells. Electron microscopy analyses indicate that the expression of full-length PDZD8 rescues the decrease in inter-organelle contacts in PDZD8 knockout cells but not PDZD8 lacking its IDR. Together, this study identifies that PDZD8 condensates at the lipid interfaces act as an adhesive framework that stitches together the neighboring organelles and supports the structural and functional integrity of inter-organelle communication.</p
Simplifying fractional polynomials in Bayesian network meta-analysis via variable powers
No full text Aim: Fractional Polynomial (FP) models are widely used in survival analysis for health technology assessment and network meta-analysis (NMA). However, current implementations rely on a fixed set of pre-specified powers, which may constrain model flexibility, limit predictive performance and increase computational cost in Bayesian settings. This study introduces and evaluates a Bayesian FP modeling approach in which the powers are estimated as continuous parameters rather than fixed, aiming to simplify model selection and improve fit. Materials & methods: Second-order Bayesian FP models were implemented in STAN, allowing the time transformation powers ( p1, p2) to be estimated from the data. Model performance was evaluated across three oncology NMA datasets; in advanced non-small-cell lung cancer, metastatic prostate cancer and early breast cancer. The performance was assessed using visual fit, leave-one-out-information-criteria, root mean square error, incremental survival estimates and computational efficiency. Validation steps included posterior predictive checks, sensitivity analyses and long-term extrapolation. Results: Across all datasets, variable power models consistently achieved better statistical fit (lower leave-one-out-information-criteria and root mean square error) than fixed power models. Incremental survival estimates were also more stable and clinically plausible, particularly in datasets with complex hazard dynamics. While variable models required slightly more time per run, the approach greatly reduced the number of required model configurations, leading to lower overall computational burden. Conclusion: Bayesian FP models with variable powers not only improve model fit and simplify model selection but also reduce structural uncertainty by replacing exhaustive grid searches with a unified, data-driven estimation of transformation powers, while retaining interpretability and computational efficiency. By producing robust, well-calibrated survival projections and streamlining model selection, this approach strengthens survival analysis for health technology assessment and supports more reliable decision-making in comparative effectiveness research. </p
Magnetic soft robots toward non-invasive diagnosis and therapy
No full textMagnetic soft robots have emerged as promising platforms for biomedical applications owing to their miniature size, mechanical compliance, andwireless actuation capabilities. Their capacity to emulate natural locomotion and navigate through conffned, dynamic, and heterogeneous environments positions them as ideal candidates for tasks such as targeted drug delivery, minimally invasive diagnostics and interventions, and in vivo sensing.Recent studies have demonstrated signiffcant potential in achieving multimodal locomotion and integrating medical functionalities. Nevertheless,the clinical translation of these systems necessitates a more comprehensiveunderstanding of their environmental adaptability, multifunctionality, andintegrated sensing performance
Hyperglycaemia does not modify the efficacy of endovascular therapy in the late time window (6–24 hours)
No full textIntroduction: Hyperglycemia is common in ischemic stroke. Admission glucose modifies the effect of endovascular therapy (EVT) in patients with ischemic stroke of the anterior circulation, who are treated 0 to 6 hours since onset. Whether this also applies for late-window EVT (6–24 hours since symptom onset or last known well) is unknown. In this study, we assessed whether admission glucose level and/or hyperglycemia modifies the EVT effect in patients with ischemic stroke of the anterior circulation in the late time window. Methods: We used data from the MR CLEAN LATE trial. The primary outcome measure was the modified Rankin Scale (mRS) score at 90 days. Secondary outcome measures were symptomatic intracranial hemorrhage and mortality at 90 days. Treatment effect modification of EVT by either glucose or hyperglycemia on admission was assessed by multiplicative interaction factors with logistic regression analysis and adjusted for potential confounders. Hyperglycemia was defined as glucose level >7.8 mmol/L on admission. Results: On admission, median glucose was 7.0 mmol/L (IQR 6.0–8.3 mmol/L), and 147 patients (32%) were hyperglycemic. We found no interaction of either hyperglycemia or serum glucose on admission with treatment effect on functional outcome (p = 0.76 and p = 0.79, respectively), symptomatic intracranial hemorrhage (p = 0.29 for hyperglycemia; p = 0.57 for glucose on admission), and for mortality (p = 0.52 for hyperglycemia; p = 0.69 for glucose on admission). Conclusion: We found no evidence for effect modification of EVT by admission glucose level or hyperglycemia in patients with acute ischemic stroke and large-vessel occlusion of the anterior circulation in the late treatment window.</p
