Over the past 35 years, my work has focused on developing and studying robotic technologies to promote hand and arm recovery after stroke. In this Point-of-View, written for a special issue honoring Steven L. Wolf, I reflect on the personal and theoretical factors that shaped my research path, and how they intersect with Steve's pioneering contributions to stroke rehabilitation. I first provide a brief overview of the personal factors that influenced my research journey. Then, I turn to theoretical factors, highlighting conceptual synergies between Constraint-Induced Movement Therapy (CIMT) and robot-assisted therapy, including the principles of dose, task-specific training, shaping, prevention of slacking, participant selection, and the critical role of proprioception. Finally, I discuss 5 implications for future directions in robotic therapy consistent with Dr. Wolf's vision of intensive, patient-centered, and mechanistically grounded therapy: (1) the use of shared principles from CIMT and robot-assisted therapy to guide the design of advanced rehabilitation technologies; (2) precision rehabilitation that prioritizes proprioception; (3) the design of practical, widely adoptable robotic systems; (4) the development of real-time biomarkers and closed-loop training systems that optimize recovery; and (5) the need for deeper collaboration with people with lived experience of disability to address unsolved challenges. Steve's impactful results, driven by his curiosity, rigor, and openness to diverse approaches, have profoundly influenced my career, the ideas I present here, and the broader field of robotic therapy.
Accurate grading and prognostic assessment of glioma requires integrating key molecular biomarkers, including IDH mutation status and the Ki-67 proliferation index. However, current radiomics studies often focus on single-task predictions and rely on manual tumor segmentation, which fails to capture intratumoral spatial heterogeneity. This study proposes an automated whole-tumor segmentation-based multimodal MRI approach integrating habitat radiomics to achieve noninvasive, multitask prediction of WHO grade, IDH mutation, Ki-67 labeling index (LI), and 2-year postoperative survival in glioma. This retrospective study enrolled 185 patients with pathologically confirmed glioma. Preoperative multimodal MRI - including T1-weighted imaging (T1WI), T2-weighted fluid-attenuated inversion recovery (T2W-FLAIR), and T1-weighted contrast-enhanced imaging (T1W CE) - was acquired for analysis. Using the uAI Research Portal platform, we performed automated whole-tumor segmentation and subsequent feature extraction, deriving 2,264 radiomics features and 61 habitat-based features. Predictive models were developed using multiple machine learning algorithms, and feature selection was rigorously performed within the training folds of a five-fold cross-validation to prevent overfitting. Model performance was evaluated using AUC, accuracy, sensitivity, and specificity, with statistical comparisons conducted performed DeLong's test. The habitat model exhibited superior sensitivity in capturing tumor heterogeneity across all four prediction tasks. Building on this, the integrated model combining habitat and conventional radiomics features, achieved the highest overall predictive performance, with AUCs of 0.916 (95% CIs: 0.858-0.975) for glioma grading, 0.877 (95% CIs: 0.828-0.926) for IDH mutation status, 0.859 (95% CIs: 0.788-0.930) for Ki-67 LI, and 0.906 (95% CIs: 0.837-0.974) for 2-year survival prediction, consistently outperforming single-modality models. SHAP interpretability analysis revealed that patient age exhibited strong correlation with tumor grade, IDH mutation status, and Ki-67 LI. Furthermore, tumor grade, IDH status, and Ki-67 LI demonstrated potential predictive value for 2-year postoperative survival. The automated habitat radiomics framework effectively quantified intratumoral spatial heterogeneity in glioma. When combined with conventional radiomics, it significantly enhanced accuracy in predicting key molecular and clinical endpoints.
Quality improvement and cost-reduction efforts among health systems have led to critical evaluation of acute dialysis delivery models. To understand the clinical and financial impact of transitioning from contracted third-party (outsourced) dialysis services to health system-owned (insourced) dialysis services. Real-world dialysis data at a regional hospital before and after insourcing using the Tablo Hemodialysis System (Outset Medical, Inc) were compared. Previous outsourcing data were compared with data from the first 12 months of insourced dialysis (presented by quarter). Analysis included number of treatments, success of treatments (by clinician determination and by successful fluid removal), and central line (catheter)-associated bloodstream infection (CLABSI) rates. Satisfaction surveys of patients and staff also were collected. Insourced dialysis achieved higher treatment success, lower CLABSI rates, and high patient and staff satisfaction. Amid a posttransition increase in the number of treatments of 279%, insourced dialysis achieved a 27% increase in treatment success by clinician determination, with more than 97% of treatments considered successful. Successful fluid removal improved from 50.8% to more than 70% across all quarters. The CLABSI rate decreased 72.7% (from 1.1 to 0.3). Retention of dialysis staff was 100% for 12 months. High staff satisfaction with their role in dialysis and insourcing was complemented with high patient satisfaction scores. Capital secured upfront was paid for within the first quarter of insourcing. Insourcing dialysis with the Tablo Hemodialysis System at a regional hospital markedly improved multiple clinical and financial metrics with high staff and patient satisfaction.
Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder. Up to 90% of children have epilepsy. Epilepsy surgery is a treatment option. However, the seizure and neurodevelopmental outcomes following this are not well defined. This study aimed to determine the outcomes for children undergoing epilepsy surgery for SWS in relation to seizure control, cognition, language, motor function and social communication. A retrospective case-note review was completed for children with SWS undergoing epilepsy surgery at Great Ormond Street Hospital from 1993 to 2022. Results of standardised developmental assessments for cognition, language and motor function were analysed. 36 children were operated on (17 hemispherotomies, 13 multilobar surgeries, 6 lobectomy/lesionectomies) with a median follow-up time of 66 months (range 8-198). 77.2% had Engel 1 outcomes (88.2% hemispherotomy, 46.2% multilobar surgery, 83.3% lobectomy/lesionectomy). Older age at surgery (OR for 1-year increase = 1.46, 95% CI 1.08-1.97, p = 0.013), but not type of surgical procedure, was independently associated with worse seizure outcomes. Good seizure control was still achieved in patients who had small residual pial angiomatoses following surgery. Most individual children showed no change or an improvement in their cognitive (67.8%) and language (72%) trajectories, although at group level this was not significant. All children undergoing hemispherotomies had a pre-existing hemiparesis. Following surgery, only 10% of children showed a decline in gross motor functional skills, but 60% had a deterioration in fine motor abilities. This is the second largest SWS epilepsy surgery case series. Epilepsy surgery for SWS resulted in good seizure control, with evidence that younger age is associated with improved outcomes. Most children had stabilisation of their developmental trajectory following surgery. Multicentre studies are needed to better define the factors associated with improved seizure and developmental outcomes.
Alzheimer's disease (AD) is characterized by progressive cognitive decline, with synaptic dysfunction as the strongest correlate of clinical symptoms. The apolipoprotein E ε4 (ApoE4) allele is the most potent genetic risk factor for late-onset AD. Beyond its roles in amyloid-β aggregation and tau hyperphosphorylation, ApoE4 disrupts synaptic integrity by perturbing lipid metabolism, neuroimmune regulation, mitochondrial dynamics, and activity-dependent plasticity. These ApoE4-driven mechanisms impair presynaptic vesicle trafficking, destabilize postsynaptic receptor and scaffolding networks (including PSD-95, SynGAP, and Shank3), and accelerate complement- and microglia-mediated synaptic pruning. Collectively, these processes converge to destabilize neuronal circuits and drive early cognitive decline. In this review, we synthesize current evidence on the molecular mechanisms by which ApoE4 compromises synaptic function, with particular emphasis on lipid microdomain instability, mitochondrial failure, and the collapse of postsynaptic density proteins. We also discuss therapeutic strategies to enhance synaptic resilience, including modulation of glutamatergic transmission, restoration of lipid homeostasis, augmentation of neurotrophic signaling, and regulation of microglial activity. Targeting synaptic preservation in APOE ε4 carriers holds promise as a disease-modifying approach to mitigate cognitive decline in AD.
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Musculoskeletal pain is common in children and adolescents and is associated with disability. Although multiple Patient-Reported Outcome Measures (PROMs) are used to assess disability, no previous review has evaluated both risk of bias and certainty of the evidence. This study aimed to appraise and summarise the evidence on PROMs for disability in children with musculoskeletal pain. We conducted a systematic review following the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN). We included studies of measurement properties of disability PROMs in children aged 3-19 years with musculoskeletal pain. Evaluation was conducted in three steps: (1) risk of bias; (2) quality criteria for each measurement property; and (3) certainty of evidence using a modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We also reported overall recommendations (strong, weak, inconclusive). We included 24 studies of 20 PROMs. Measurement properties ranged from very low certainty of evidence of insufficient to high certainty evidence of sufficient measurement properties. The Functional Disability Inventory (FDI) had a weak recommendation in favour of use, while the Oswestry Disability Index (ODI) and Patient-Reported Outcomes Measurement Information System (PROMIS) had weak recommendations against use. There are 20 PROMs available to measure disability in children and adolescents with musculoskeletal pain. Overall, measurement properties showed considerable variability, with most instruments supported by low or very low certainty of evidence. Consequently, there is insufficient evidence to recommend most PROMs for use. The FDI appears to be the most promising instrument.
Understanding drivers of tuberculosis (TB) associated lung pathological damage is vital in identifying targets for host directed therapies (HDT). NETosis is a neutrophil specific cell death characterized by release of neutrophil extracellular traps (NETs). The role of NETosis in TB-associated lung damage and disease pathogenesis is still poorly understood. We analysed human lung TB granuloma samples using a proteomics approach, which revealed enrichment of neutrophil-associated proteins in necrotic regions of caseous and cavitary granulomas. Using immunohistochemistry (IHC), we validated the abundance of neutrophil-associated proteins, including myeloperoxidase (MPO), cytochrome b-245 beta chain (CYBB) and neutrophil cytosolic factor 1(NCF1), as well as NETosis markers, neutrophil elastase (NE) and citrullinated H3, in necrotizing caseum of human TB granulomas. MPO protein expression was also more abundant in the plasma of TB patients compared to healthy and latently infected (LTBI) participants. MPO directly correlated with an inflammatory disease marker, IP-10. In addition, MPO and IP-10 colocalized in caseous lesions. In-vitro drug inhibition assays were used to investigate potential drivers of NETosis, with pharmaceutical inhibition of MPO, NE and CYBB resulting in reduction of NETosis induced by Mycobacterium tuberculosis (Mtb). Using RT-qPCR we analysed the expression of 18 neutrophil associated genes in the blood of healthy (n = 20), latent TB infection (LTBI) (n = 20) and TB (n = 30) participants. We found that MPO, NCF1 and NCF2 were upregulated in the TB group. Furthermore, the NETosis-associated genes were induced in a human standardized antigen challenge model. Our data shows evidence of NETosis as an associate of lung pathological damage in TB and identifies key drivers of the neutrophil cell death that can be intercepted as potential HDT targets to reduce neutrophil driven lung pathological damage.
Interleukin-17A (IL-17A) is a key Th17 cytokine involved in mucosal defense and chronic inflammation and serves as an important biomarker and therapeutic target in autoimmune, cardiovascular, and infectious diseases. Emerging evidence indicates that immune regulation may differ by sex, which may influence disease susceptibility, biomarker interpretation, and treatment response. However, few studies have examined sex-specific determinants of IL-17A. This study aimed to identify the sociodemographic, clinical, and inflammatory correlates of circulating IL-17A, with a specific focus on elucidating sex-specific determinants. We conducted a cross-sectional study in a cohort of adults attending routine clinic from Livingstone University Teaching Hospital in Zambia. Plasma levels of IL-17A and a panel of inflammatory cytokines were measured. Sociodemographic, metabolic and clinical data, including HIV status and ART regimen, were collected. Sex-stratified multiple linear regression models were used to identify independent correlates of IL-17A levels with statistical significance p < 0.05. A total of 225 participants were recruited, comprising 71 males and 154 females, with median ages 50 (41, 59) vs. 48 (40, 58) years, respectively. Distinct sex-specific factors associated with IL-17A were identified. In males, IL-17A levels were significantly associated with a recognized inflammatory cytokine network, including positive correlations with IL-6 (Beta: 43.96, 95% CI: 30.58-57.34, p < 0.001) and IL-1β (Beta: 0.02, 95% CI: 0.02-0.03, p < 0.001), and a negative association with IFN-γ (Beta: -1.21, 95% CI: -1.65 - -0.77, p < 0.001). However, living with HIV was not a predictor of IL-17A (Beta: -1248.07, 95% CI: -2752.35-256.21, p = 0.101). Among females, none of the cytokines or HIV status predicted IL-17A; instead, plasma potassium (Beta: 9.81, 95% CI: 5.31-14.30, p < 0.001) was the only significant determinant of IL-17A. The determinants of IL-17A are fundamentally different between males and females. These findings underscore the importance of considering biological sex as a key variable in immunology research. They suggest that IL-17A may require sex-specific interpretation as a biomarker of inflammation, particularly in HIV-associated and cardiometabolic conditions, and highlight the potential for sex-tailored therapeutic strategies targeting IL-17A-related pathways. Further studies are needed to validate these findings and explore their mechanistic and clinical implications.
Objective: This paper examines the development of an evidence-based health communication campaign about college students' perceptions of alcohol use and sexual consent. Participants: Data were collected in three phases from two public Southwestern universities: 131 undergraduate students in phase 1, 264 in phase 2, and 21 in phase 3 interviews. Methods: Phase 1 involved an online survey assessing alcohol use, sexual activity, and consent perceptions. Phase 2 tested campaign concepts, with students evaluating content effectiveness, alcohol-related beliefs, and sexual behaviors. Phase 3 refined and piloted "Your Level" vs. "Their Level" and "Q&A Cards," through social media posts and online interviews. Results: Students exposed to the concept, "Your Level" vs. "Their Level" endorsed marginally lower intoxicated consent thresholds than those who were not, indicating an implicit understanding of its consent-related content. Students also emphasized normalizing alcohol and consent conversations and consistent language across campaigns. Both concepts were seen as effective in showing how alcohol impairs consent. Conclusions: Interventions should integrate alcohol and consent in communication efforts.
Donor-derived cell-free DNA (dd-cfDNA) is a validated marker of graft injury following isolated heart or lung transplantation. However, no such studies exist for heart-lung transplant (HLTx) recipients. HLTx recipients at a single center were screened for enrollment between August 2022 and September 2024. Heart transplant (HTx) and lung transplant (LTx) recipients from the same center served as comparison groups. Plasma dd-cfDNA samples were collected before surveillance bronchoscopies and clinically indicated evaluation for graft dysfunction during the first-year post-transplant. Stable patients demonstrated no evidence of rejection, infection, or injury at any time. Pulmonary function test results (PFTs) were monitored and compared. In total, 92 HTx, 39 LTx, and 10 HLTx recipients were enrolled. The HLTx cohort had a significantly different dd-cfDNA profile compared to LTx and HTx (median dd-cfDNA in HLTx: 0.14, LTx: 0.34, and HTx: 0.06, p<0.001), with values lower than LTx in both stable and unstable groups. One-year post-transplant, 31% of HLTx patients were unstable, compared to 84% of LTx recipients. Acute rejection occurred in 10%, 10.5%, and 22.3%, of the HLTx, HTx, and LTx cohorts, respectively. PFTs at 1-year were also significantly different; in the HLTx group, percent predicted FEV1 values were increasing, but these parameters were decreasing in the LTx cohort. This study indicates that dd-cfDNA could be a useful tool for monitoring allograft health following HLTx, though sample size was limited. Further research is underway to elucidate the mechanisms that account for these findings and to establish thresholds for detecting graft injury in this distinct cohort.
Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) colon cancers are associated with reduced lymph node (LN) metastasis and improved outcomes in early-stage disease; however, whether these associations vary by patient age remains unclear. Using the National Cancer Database (2018-2021), we identified 116,623 patients with stage I-III colon adenocarcinoma undergoing upfront surgery and stratified them by age (<65 vs. ≥65 years) and MSI status (MSI-H/dMMR vs. microsatellite stable). Multivariable linear regression assessed LN positivity and lymph node ratio, and Cox proportional hazards models evaluated overall survival, including an interaction term between age and MSI status. MSI-H tumors were more common in older patients (24.9% vs. 13.6%). MSI-H status was independently associated with 0.53 fewer positive lymph nodes (95% CI -0.73 to -0.34), and older age was associated with 0.37 fewer positive lymph nodes (95% CI -0.47 to -0.28). A significant interaction between age and MSI status demonstrated attenuation of the MSI-associated nodal protection in older adults. In node-negative disease, MSI-H was associated with improved overall survival in younger but not older patients, whereas in stage III disease MSI-H was associated with worse survival in older patients. The age-MSI interaction remained significant in adjusted survival models. These findings suggest that the prognostic and biologic implications of MSI-H in stage I-III colon cancer are meaningfully modified by age and should be interpreted within an age-specific context.
Malnutrition is a recognized but insufficiently investigated concern in children with childhood interstitial lung diseases (chILD). The relationship between nutritional status and pulmonary function in this population remains poorly understood. This study aimed to evaluate the frequency and impact of malnutrition in chILD and to identify associated clinical factors. We analyzed baseline and follow-up data from the chILD-EU registry, including anthropometric measurements, disease severity scores, pulmonary function tests, and treatment information. Malnutrition was defined as a weight-for-age (WFA) z-score < -2. Multivariable linear regression models were used to assess the association between malnutrition and lung function after adjustment for potential confounders. Longitudinal mixed-effects models were applied to evaluate the relationship between time-varying nutritional status and lung function over time. A total of 3351 visits from 766 children were analyzed. At baseline, 38.9% of children were malnourished. Children with malnutrition had significantly lower lung function compared with those without malnutrition (both p < 0.001). In multivariable analyses adjusting for age, sex, prematurity, diagnostic category, and disease severity, malnutrition remained independently associated with reduced lung function (zFEV1 β = -0.83, p = 0.007; zFVC β = -1.35, p < 0.001). In longitudinal mixed-effects models including baseline and follow-up visits, improvements in WFA z-scores were associated with improved lung function over time (zFEV1 β = 0.33, p < 0.001; zFVC β = 0.37, p < 0.001). Malnutrition is common among children with chILD and is independently associated with impaired lung function and greater disease severity. Improvements in nutritional status are associated with improved pulmonary outcomes during follow-up, highlighting the importance of routine nutritional monitoring and multidisciplinary care.
Understanding the evolution of life-history strategies within a taxonomic guild offers critical insights into how species allocate energy toward growth, reproduction, and survival in response to environmental pressures. We examined 42 odontocete whale species using six key life-history traits and three major environmental variables- latitude, bathymetry, and sea ice -to identify broad patterns in ecological and evolutionary strategies. While controlling for body size and phylogenetic relatedness, we used archetypal clustering analysis to identify three groups of species according to shared life-history characteristics: bet-hedging, slow, and fast. We then assessed environmental associations among these three life-history strategies. Ancestral state reconstruction was used to disentangle the roles of phylogenetic constraint and ecological adaptation in shaping these strategies. Our results reveal convergence in life-history traits among distantly related species occupying deep, offshore habitats, suggesting that environmental similarity can drive parallel evolutionary outcomes. In contrast, species inhabiting more ephemeral, high-latitude environments with seasonal sea ice exhibit lineage-specific adaptations, reflecting a stronger influence of evolutionary history. These findings offer a framework for tailoring conservation strategies to the distinct ecological profiles of odontocete groups, accounting for factors such as exposure to anthropogenic stressors, reliance on specialized habitats, and inherently slow recovery rates following human exploitation.
Mechanical ventilation is lifesaving yet harmful when paired with deep sedation and immobility. The ABCDEF, or intensive care unit liberation bundle (assessment and treatment of pain, spontaneous awakening and breathing trials, judicious choice of analgesia/sedation, delirium prevention/management, early mobility, and family engagement) mitigates these risks, improving survival, reducing delirium and coma, shortening time receiving ventilation, and promoting recovery. This article synthesizes evidence for the awake-and-walking intensive care unit, in which wakefulness and mobility are the default. We define the role of the advanced practice registered nurse in reliable implementation of this model: embedding bundle elements into workflows, aligning sedation and mobility targets, coordinating interprofessional teams, and driving culture change through measurement and feedback. A case example illustrates a patient's trajectory under high versus low adherence. We close with pragmatic strategies to overcome workflow fragmentation, staffing variability, and safety concerns, mapping barriers to solutions such as protocol standardization, nurse-respiratory therapist coleadership, daily goal alignment, and data transparency.
Developing tuberculosis drug regimens requires coordinated discovery of multiple, mechanistically distinct agents, which challenge traditional single-asset models. The Tuberculosis Drug Accelerator (TBDA) was established as a multi-organizational consortium to enable collaborative discovery across academia, industry and research institutions. Over more than a decade, the TBDA has demonstrated how such collaborations can align incentives, manage uncertainty and maintain portfolio discipline. This manuscript examines the operational and governance mechanisms that enable sustained collaboration. Although shaped by a global health context, this model can inform collaborative drug discovery efforts in other research settings requiring coordinated, multi-institutional approaches.
Nutrition is critical for diabetes management, yet evidence about healthcare providers' knowledge, attitudes, and practices (KAP) in sub-Saharan Africa, including the Democratic Republic of the Congo (DRC), remains limited. We evaluated healthcare providers' KAP related to nutrition management for patients with type 2 diabetes in Kinshasa and explored links between knowledge, attitudes, and practice. We conducted a descriptive correlational cross-sectional study between November and December 2024 among healthcare providers in diabetes care in Kinshasa, DRC. Using probabilistic multi-stage sampling of healthcare facilities across all 35 health zones, 877 healthcare providers were interviewed. KAP scales were scored across sociodemographic and professional characteristics and family history of diabetes. Structural equation modelling estimated direct and indirect effects among knowledge, attitude, and practice and evaluated determinants. Among 877 healthcare providers, there were 267 doctors, 574 nurses, and 36 nutritionists. The median age was 39 years (IQR = 32-46), and a minority had received diabetes-related training within the past 12 months (232/877; 26%). Mean scores for knowledge were 11.9/19 (SD = 2.6), for attitude 11.9/14 (SD = 2.9), and for practice 10.0/17 (SD = 5.4). While most healthcare providers (809/877; 89%) agreed that nutrition is fundamental for diabetes care, many healthcare providers viewed nutritional management for hospitalised patients as the nutritionist's sole responsibility. Many healthcare providers reported that they did not utilise any record form for nutritional assessment (499/877; 56.9%) or any record for nutrition-related issues or diagnoses (446/877; 50.9%). Structural equation modelling showed that both knowledge (β = 0.54, p < 0.001) and attitudes' scores (β = 0.81, p < 0.001) significantly influenced practices, with attitude mediating the effect of knowledge on practice. Professional category and training were the strongest predictors of higher KAP scores, whereas female sex was negatively associated with scores for both knowledge and attitude. The study revealed major gaps in healthcare providers' knowledge and practices on nutrition management in Kinshasa, shaped by both knowledge and attitudes. Differences by profession and sex highlight training inequities. Despite its cross-sectional and self-reported limitations, the study highlights the need for targeted, context-specific interventions to strengthen frontline healthcare providers' skills and attitudes on that aspect in urban sub-Saharan Africa.
Overdrainage of the cerebrospinal fluid (CSF) is a known complication of hydrocephalus shunt treatment. The concept of CSF overdrainage has evolved alongside advancements in shunt technology and hydrocephalus management. A systematic literature review identified 22 descriptions of CSF overdrainage, highlighting the lack of a universally accepted definition. To address this ambiguity, we conducted a multicentre consensus study to establish a clinically relevant definition of CSF overdrainage that can guide future research and clinical decision-making. A modified Delphi consensus process was conducted with 18 neurosurgeons and neuroscientists specialising in hydrocephalus from centres in Africa, Europe, India, and USA. Participants had at least ten years of clinical experience and/or significant publications in the field. The previous systematic literature review identified 32 clinical and radiological manifestations of CSF overdrainage, which were evaluated by the consensus-panel. The process included multiple rounds of structured questionnaires and virtual discussions. Consensus was achieved if a manifestation gained more than 70% support throughout the process. Finally, through iterative refinement the definitions were established. The panel agreed that CSF overdrainage presents differently in various patient populations and should be defined by cardinal symptoms/findings rather than additional less frequent symptoms/findings. Three age-dependent definitions were established for paediatric patients: infants (age < 1 year), children with a growing skull (age 1 to 7 years), and children with a fixed skull (age > 7 years). A separate definition was formulated for adults (age ≥ 18 years). Across all age groups, CSF overdrainage was characterised by posture-related symptoms, primarily headache or in infants' irritability consistent with headache relieved in supine position. Radiological findings include ventricular collapse (age < 18 years) and non-traumatic subdural collections (all age groups). Consensus-based definitions provide a standardised framework for future research and clinical management of hydrocephalus. It addresses the longstanding variability in diagnosis and treatment of CSF overdrainage in shunt-treated patients.
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This perspective marks the commemoration of the 2024 Nobel Prize in Medicine for miRNA discovery and reflects on more than two decades of research linking miRNAs to islet biology and diabetes. We very briefly summarize key roles of islet miRNAs in β-cell development, function, and immune interactions and identify major gaps in current knowledge. We discuss emerging concepts in miRNA regulation, cellular heterogeneity, and therapeutic targeting, alongside ongoing challenges in biomarker validation. Our view underscores that integrating mechanistic, single-cell, and translational approaches will be essential to advance miRNA-based therapies.