Collaborative and game-based pedagogical approaches are increasingly applied in physical education (PE) to enhance engagement and support meaningful movement learning. However, empirical evidence remains fragmented across educational levels, instructional models, outcome domains, and methodological designs, limiting coherent synthesis and interpretation. This systematic review followed the PRISMA 2020 guide-lines and was registered in PROSPERO (no. CRD420261306696). It aimed to map quasiexperimental evidence on collaborative and game-based pedagogies implemented in formal Physical Education contexts, as well as to synthesize their associations with movement-related outcomes. A systematic search of Scopus, Web of Science, PubMed, ERIC, and SPORTDiscus was conducted for studies published between January 2011 and December 2025. Seventeen peer-reviewed studies met predefined PICOS-based inclusion criteria. Eligible studies implemented collaborative or game-based instructional models within PE or Physical Education Teacher Education contexts and assessed movement-related outcomes. Data were synthesised using narrative synthesis supported by structured descriptive evidence mapping. Due to substantial heterogeneity in study designs, participant characteristics, pedagogical approaches, and outcome measures, quantitative meta-analysis was not considered appropriate. Methodological quality was appraised using an adapted Joanna Briggs Institute checklist. Seventeen quasi-experimental studies were included, involving preschool (n = 1), primary (n = 4), secondary (n = 4), and university/PETE populations (n = 8). Pedagogical models included cooperative learning, peer teaching, Team Games Tournament, exergame-based learning, and structured game-based movement models (n = 3 each), while tactical or games-based approaches were less frequently examined (n = 2). Sport-specific technical skills were the most commonly assessed outcomes (35.3%), followed by fundamental movement skills, motor competence, game performance, and psychosocial/fitness-related outcomes. Motor or game-performance improvements were reported in 41.2% of studies, mixed effects in 29.4%, and no superior motor learning in 29.4%, with no negative outcomes reported. Collaborative and game-based pedagogies appear pedagogically viable in PE, particularly when instructional design aligns with targeted movement outcomes. However, heterogeneity in study design, outcome measurement, and participant age limits comparative inference. Future research should prioritise adolescent populations, longitudinal designs, and ecologically valid movement assessments. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261306696.
Spontaneous movement analysis provides valuable information about the maturation of the central nervous system and the emergence of motor control strategies in very young babies. Nonlinear measures capture dynamic aspects of movement that cannot be represented by linear methods. However, their implementation in clinical practice faces challenges, including the lack of standardized protocols and accessible tools for routine use. This scoping review aimed to map and characterize the nonlinear measures used to analyze spontaneous infant movement, including assessment context, instruments, data collection protocols, and main variables. The review followed JBI methodology and PRISMA-ScR guidelines. Searches were conducted in PubMed®, Web of Science™, IEEE Xplore®, ScienceDirect®, and Google Scholar for studies published from 1 January 2005 to 31 December 2025. Of 1166 records identified, 18 met the inclusion criteria. The nonlinear measures were grouped into five main methodological families: entropy-based measures (n = 10), state-space and dynamical systems measures (n = 4), recurrence-based analysis (n = 3), symbolic and discrete-state approaches (n = 3), and variance and frequency-based nonlinear descriptors (n = 1). Studies were conducted in laboratory settings (n = 6) and in hospital and/or home environments (n = 10). Two studies did not clearly specify the assessment context. Kinematic assessment was mainly performed using video-based systems (n = 7), accelerometers (n = 4), and wearable sensors (n = 2), with most studies focusing on the upper and lower limbs. Several investigations extended beyond single-joint analyses to examine inter-limb relationships and whole-body configurations, capturing spatial coordination patterns across multiple body segments. Kinetic assessment was conducted using pressure mats (n = 4) and force platforms (n = 1), with the center of pressure displacement as the primary outcome. Future research should prioritise methodological harmonisation and theoretical clarity. Consensus is needed regarding minimal data requirements, parameter selection, and reporting standards for commonly used nonlinear measures. Studies should also move beyond single-metric approaches and adopt multivariate frameworks that integrate complementary nonlinear metrics. The absence of standardised acquisition and analytical protocols currently limits cross-study comparability and hinders the clinical translation of nonlinear movement metrics as objective tools for early neurodevelopmental assessment.
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Engaging in moderate-to-vigorous physical activity (MVPA) in early childhood can have both immediate and long-term health benefits. Strategies for consistently supporting this are currently unknown, largely due to the vast number of potentially interrelated and dynamic contributing factors that may also be heterogenous across children. We developed an agent-based model (ABM) that represents children ages 3-9 who can engage in MVPA in a variety of settings in which they spend time. Our model incorporates key theoretical constructs identified in the literature and is grounded in high-quality empirical evidence, primarily participant data from a cohort-based randomized controlled trial with extensive longitudinal accelerometry measurement. We assess the ABM's ability to reproduce patterns of MVPA observed in the cohort. We uncovered a specific model representation of key pathways and settings involved in MVPA for this age group that can closely reproduce real-world MVPA across multiple a priori assessment metrics. This specification provides new insights into modeled contributors to MVPA. Within our model, the most important within-model pathway driving MVPA for girls is the quality of the built environment, while, for boys, it is the social environment; given the relative availability of the two, this might explain observed differences in MVPA in real-world settings. In addition to immediate insights, this article provides proof of principle for a powerful tool that can further explore the etiology of childhood MVPA and inform practices and policies to positively affect early childhood PA, setting the stage for lifelong health.
Continuous subcutaneous foslevodopa/foscarbidopa (FLD/FCD) is the first 24-h levodopa-based subcutaneous infusion therapy for advanced Parkinson's disease (PD). Real-world data from the Middle East region are absent. To report the first Middle Eastern clinical experience with foslevodopa/foscarbidopa, evaluating motor and non-motor outcomes, safety profile, and treatment continuation rates in routine clinical practice. Retrospective, single-center, observational cohort study. Twenty-eight consecutive patients with advanced PD underwent inpatient foslevodopa/foscarbidopa initiation between January 2025 and January 2026 at a quaternary academic medical center in Abu Dhabi, United Arab Emirates. Primary outcomes were Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, daily OFF/ON hours, and Hoehn and Yahr stage; secondary outcomes included Non-Motor Symptoms Scale (NMSS) total and domain scores and MDS-UPDRS Parts I and II. Motor assessments were conducted in the practically defined OFF state at baseline and in the ON state at follow-up on stable foslevodopa/foscarbidopa therapy. Safety was assessed by systematic recording of adverse events. Paired comparisons used Wilcoxon signed-rank tests. Mean age was 61.3 ± 13.5 years; disease duration 10.1 ± 7.4 years; baseline levodopa equivalent daily dose 1018 ± 574 mg. MDS-UPDRS Part III improved from 50.7 ± 14.5 (OFF-state baseline) to 27.1 ± 13.6 (ON-state follow-up; change -23.6 ± 8.3, p < 0.0001), representing elimination of wearing-off disability. Daily OFF time fell from 2.8 ± 1.4 to 0.9 ± 0.6 h (-1.9 ± 1.4 h; p < 0.0001), and good ON time increased by 2.0 ± 1.3 h (p < 0.0001). Hoehn and Yahr stage improved from median 3 (interquartile range (IQR) 3-4) to 2 (IQR 2-3; p < 0.0001). Non-motor symptom burden decreased substantially: MDS-UPDRS Parts I and II fell by 22.7 ± 9.3 points (p = 0.001) and NMSS total score by 29.7 ± 18.7 points (~49% reduction; p = 0.0007). Infusion site reactions occurred in 22 patients (79%) but were generally manageable. Six patients (21%) discontinued therapy (median 4.8 months), primarily because of skin reactions or compliance difficulties. Foslevodopa/foscarbidopa produced clinically meaningful improvements in motor fluctuations and non-motor symptom burden in this first Middle Eastern real-world cohort, supporting its role as an effective and feasible non-surgical device-aided therapy for advanced PD. The first Middle Eastern experience with a new non-surgical pump therapy for advanced Parkinson’s disease Parkinson’s disease causes shaking, stiffness, and slow movement that worsens over time. As the disease advances, standard levodopa tablets stop working smoothly, leaving patients unable to move or function for unpredictable periods each day. Existing advanced treatments, including brain surgery and intestinal tube pumps, require invasive procedures that many patients cannot undergo due to age, cognitive difficulties, or other medical reasons. Foslevodopa/foscarbidopa is a newly approved therapy that delivers levodopa continuously through a small wearable pump placed under the skin, requiring no surgery. This study reports the first real-world experience with this treatment in the Middle East. Twenty-eight patients with advanced Parkinson’s disease were treated at a specialist centre in Abu Dhabi, UAE, and followed for a median of nine months. Patients spent nearly two fewer hours per day unable to move and gained two additional hours of good functional time daily. Motor severity improved substantially. Non-motor symptoms, including anxiety, sleep disturbance, depression, and cognitive difficulties, improved by approximately 49%. Skin reactions at the pump site were common but resolved in all cases. Only 21% of patients discontinued therapy, and 75% reported satisfaction with treatment. These findings show that foslevodopa/foscarbidopa is effective and well-tolerated in a diverse real-world population, supporting its use beyond the settings studied in clinical trials.
ConspectusEnzymes and nucleic acid processing machines are among the most sophisticated molecules evolved by nature. These include several vital enzymes such as polymerases, nucleases, topoisomerases, and RNA enzymes. These enzymes exhibit complex structures and multicomponent assemblies that enable an exceptional efficiency and specificity in carrying out the fundamental chemical reactions required for life. Yet, these structures pose a challenge to our understanding of their catalytic precision, as this requires atomistic insight into how they operate on DNA or RNA. Indeed, the static or quasi-static view from experiments fails to fully explore the conformational space that these enzymes traverse during catalysis. Thus, advanced molecular simulation techniques are increasingly integrated with experimental results to overcome such sampling limitations and to explore the configurational space, thereby defining the functional dynamics of structural motions and rearrangements that would otherwise remain unclear.In this Account, I will examine how atomistic multiscale molecular simulations and free energy calculations─recently coupled with AI-guided enhanced sampling methods─have contributed to clarifying enzymatic mechanisms that could only be hypothesized by examining structures, as evidenced by increasingly complex structural biology results. This is a time when we can simulate ultralarge realistic model systems comprising proteins, nucleic acids, ions, and water molecules, all of which are critical components for enzymatic function. Remarkably, such modeling and simulations can nowadays enable the prospective exploration of increasingly structurally complex systems.In this scenario, there is today a relevant body of work that defines function through motion as a key element in these enzymes. My group has generated a broad collection of results on a range of nucleic acid processing enzymes, from polymerases to nucleases and RNA enzymes, which altogether highlight how dynamics define function, with specific residues─often evolutionarily conserved and localized in the second coordination shell of the catalytic core─that are strategically positioned to operate in a cooperative and highly coordinated fashion for specific enzymatic actions on nucleic acids. These coordinated residue motions, near the reaction center, appear distinct from large allosteric movements of distal domains. Instead, they resemble finely tuned, small-scale mechanisms that marry complexity with the precise, clocklike efficiency evolution has built into the catalytic core. How such elaborate enzymatic architectures move-to-function, captured and demonstrated by the most recent computational work and structural data, will therefore be the core topic discussed in this Account. While the concept of "function through motion" can obviously be extended to other catalytic systems, what is particularly remarkable about these enzymes─even if not unique─is that their functional complexity is handled with extraordinary accuracy through precise motions, despite the system's architectural complexity, on the move. These recent mechanistic findings also provide insights into how to engineer or modulate these enzymes, with implications for several scientific activities centered on nucleic acid chemistry.
First mobilization plays a critical role in reducing and preventing common postoperative complications such as atelectasis, deep vein thrombosis, and constipation following arthroplasty. However, many patients experience substantial fear and anxiety related to their first postoperative mobilization. Kinesiophobia associated with fear of movement may negatively affect patients' quality of life and delay the mobilization process. Consequently, avoidance of mobilization can lead to decreased physical activity and functional independence, resulting in increased dependency on others. In this context, nurses play a crucial role in alleviating patients' fears, ensuring a safe mobilization process, and enhancing motivation. Therefore, the aim of this study was to evaluate the effectiveness of a first mobilization protocol developed for patients undergoing total knee arthroplasty. This was a single-center, parallel-group, single-blind randomized controlled trial. The study sample consisted of 78 patients (control: 39, intervention: 39). The study was conducted at the Orthopedics and Traumatology Clinic of one of the University Health Research and Application Centers (blinded for peer review). Data were collected via the Patient Information Form, State-Trait Anxiety Inventory, Tampa Kinesiophobia Scale, and First Mobilization-Related Symptoms Assessment Form. Additionally, the first mobilization protocol was applied to the intervention group. The data obtained from the participants were analyzed via SPSS 26.0 software. Statistical significance was set at p<0.05. The degree of feeling ready for first standing was greater in the intervention group than in the control group. Participants in the intervention group completed both the first and last mobilization in a shorter time and had lower levels of anxiety, stress, fear of falling, and fear of being unable to walk or move, with statistically significant differences observed between the groups. The first mobilization protocol applied to patients who underwent knee arthroplasty was effective in terms of their ability to feel ready, mobilization time, anxiety, stress, fear of falling, and fear of not being able to walk/move. The application of the first mobilization protocol developed by orthopedics and trauma nurses to patients undergoing knee arthroplasty should be expanded. This study was retrospectively registered at Clinicaltrials.gov on 12.03.2024 (Clinical Trials ID: NCT06268899).
Animals move through their environments using remarkably diverse locomotor behaviors, which are critical for their survival and success. All movement, including locomotion, requires the coordinated function of three components: the central nervous system (CNS), the peripheral nervous system (PNS), and the musculature. Although evolutionary change in any one of these components can alter locomotion, how these changes arise and combine to generate behavioral diversity remains poorly understood. Larval insects are an exceptional system for addressing this question: they combine extensive behavioral and morphological diversity with relatively simple, stereotyped anatomy, enabling cell-level homology inferences and quantitative cross-tissue comparisons. We first review anatomical evidence for the long-standing peripheral change hypothesis, which posits that locomotor diversity is primarily driven by modifications to peripheral structures, such as muscles, while central circuits remain conserved. We then propose an alternative hypothesis, the motor neuron bottleneck hypothesis, which draws on comparative neurodevelopmental data to suggest that motor neurons are disproportionately conserved relative to both upstream sensory neurons and interneurons and downstream muscles. Finally, we consider how connections are maintained between the CNS, PNS, and musculature when these components change in number. Throughout, we assess relative rates of evolutionary change in cell number across nested phylogenetic scales, from the Drosophila genus to the Diptera order to the Holometabola supraorder. By integrating anatomical, developmental, and functional perspectives, larval insects emerge as a powerful comparative model for uncovering general evolutionary principles.
Background/Objectives: Hospital-wide bed pooling is widely used in bed-management reform to reduce ward-level mismatch and improve the use of scarce inpatient capacity. However, formally pooled beds are not automatically usable beds. Cross-ward reassignment may require coordination, placement judgment, and timely execution, especially when several wards are under pressure. This study examines hospital bed governance as a healthcare management problem of where to draw the boundary between local protection and centralized pooling. Methods: We develop an α-based governance framework that places full decentralization, bounded centralization, and full centralization within a common design space. The parameter α determines how much ward-level capacity is pooled and how much remains locally protected. The analysis first establishes a frictionless pooling benchmark, and then introduces coordination friction, stress-state pooled-allocation imperfection, and the protective value of local capacity. Scenario-based computational experiments examine the mechanism across operating conditions, alternative friction specifications, and multi-ward extensions. Results: In the frictionless benchmark, full centralization weakly dominates because it has the broadest feasible allocation set. When pooled allocation remains fully effective, full centralization is not substantively outperformed. Coordination friction can move the raw maximizing boundary inward, but this movement does not necessarily imply a meaningful improvement over full centralization. When reassignment becomes less reliable in high-pressure states, however, an interior governance boundary can become substantively attractive by preserving some locally accessible capacity. Conclusions: The findings do not reject centralized pooling. They suggest that bed reform should evaluate both the formal scope of pooling and the operational usability of pooled capacity under pressure.
Research data services (RDS) have expanded in academic libraries but can be challenging to develop, particularly in teaching-intensive and less-resourced institutions. Learning communities offer a promising model for building skills, fostering collaboration, and aligning services with local needs. This case report describes the development and implementation of three learning communities-a library group, a faculty group, and a student group-at a teaching-focused institution. These communities brought together library professionals, faculty, and students from diverse disciplines-including health sciences, education, data science, and engineering-to collaboratively explore the All of Us dataset. By working with the same dataset, participants were able to move quickly from abstract concepts to hands-on practice, while developing a shared understanding of tools, workflows, and challenges. The learning communities also served as platforms for building institutional capacity in data-intensive research. The learning communities model proved to be an effective strategy for fostering cross-disciplinary collaboration, promoting data literacy, and building institutional readiness to support research using the All of Us dataset. By centering on local expertise, learning communities provide a sustainable, resource-conscious framework for developing RDS. This approach also demonstrates how academic libraries can act as conveners and catalysts for equitable data engagement. Lessons learned from this case may inform similar efforts at other institutions seeking to build collaborative, inclusive models for engaging with various data resources.
As Denmark continues to move towards a more decarbonized future, Power-to-X (PtX) technologies are becoming an important part of green energy and fuel. These technologies also have significant impacts on land and social equity. This study combines spatial analysis, qualitative case studies, and stakeholder mapping to analyze how PtX expansion interacts with land allocation and existing socio-economic inequalities within Denmark. Spatial mapping using geographical information systems (GIS) reveals that PtX infrastructure is more heavily sited in rural areas, heightening competition for land, environmental impacts, and economic impacts on local communities. These burdens affect rural communities more than urban ones. Case studies of three PtX facilities highlight how different planning and community engagement strategies produce varying outcomes. Stakeholder analysis identifies key tensions between developer actions and public response. Findings show that, while PtX can improve Denmark's energy security, a proactive policy is needed to ensure benefits are shared equally and community concerns are addressed. Recommendations include mandating early community engagement, prioritizing existing industrial sites, strengthening local benefit-sharing programs, enhancing environmental and social impact assessments, and expanding community education. This approach is crucial for Denmark to integrate PtX at scale while addressing spatial and socio-economic tradeoffs.
Heatwaves are becoming more frequent, intense, and prolonged in Europe, creating a predictable clinical stressor for multimorbid patients and increasing pressure on Internal Medicine services. Current disease-specific guidelines provide limited practical guidance on how to prevent heat-related admissions and decompensations in patients exposed to polypharmacy, frailty, chronic kidney disease, heart failure, diabetes, cognitive impairment, or social vulnerability. This Editorial proposes the concept of thermopharmacological frailty, a dynamic state in which environmental heat modifies the risk-benefit balance of chronic medication by impairing thermoregulation, hydration, renal perfusion, cardiovascular compensation, cognition, and metabolic stability. We argue that heatwaves should be approached as drug-environment interaction periods, not merely as meteorological events. To move beyond generic heat advice, we outline a pragmatic Internal Medicine pathway based on anticipatory identification of vulnerable patients, mechanism-based medication review, early recognition of warning signals, selective monitoring, and explicit restart criteria after temporary treatment adjustments. Preventing heat-related acute kidney injury, hypotension, falls, delirium, dysglycaemia, heart failure decompensation, and medication toxicity will require exposure-aware medication safety protocols embedded in ambulatory, inpatient, and transitional Internal Medicine care.
The Arp2/3 complex has long been considered to only assemble branched actin structures in the cell (lamellipodia, endocytic patches, comet tails, and many more). We show for the first time by single-molecule tracking (SMT) that the Arp2/3 complex and SPIN90, which activates Arp2/3 complex to nucleate unbranched filaments, bind to and move in the basal cortex with stress fibers and focal adhesions (FA) that, unlike known sites of Arp2/3 enrichment, employ linear actin bundles. SPIN90 knockout in U2OS cells significantly increases the rate of collective cell migration while decreasing cellular traction (myosin-II and actin speeds) and adhesion (FA size and maturation markers). SPIN90's SH3 domain, similar to its adapter protein Nck1, shows enrichment in FAs, suggesting a possible location for SPIN90-Arp2/3 complex activity. Together, our findings indicate that SPIN90-Arp2/3 nucleated filaments also function in stress fibers where they help define the mechanics of traction and adhesion to regulate cell motility. The Arp2/3 complex, the branched actin nucleator, drives pushing forces in the cytoplasm, yet its diffuse cortical localization has obscured its functions within unbranched structures. In conventional microscopy, associations of molecules with specific structures are impossible to verify when there is little enrichment over the cytoplasm. Whereas other methods fail to provide convincing evidence of such associations, we used single molecule tracking in live cells to identify molecules that track the motions of stress fibers. Thus, we were able to discover that the Arp2/3 complex and SPIN90, proteins whose roles in cell biology have been thus far limited to branched actin networks, directly integrate within the unbranched stress fiber network to promote cell adhesion and traction for cell migration.
Health literacy is acknowledged as a critical determinant of equitable health outcomes. However, its social patterning among populations experiencing legal precarity, irregular mobility, and administrative exclusion remains insufficiently examined in the sub-Saharan African context, particularly in Ghana. This study addresses this gap by examining health literacy among unaccompanied migrants and persons prone to statelessness in Ghana. Data were derived from a cross-sectional survey conducted in two purposively selected districts in Ghana, characterized by mobile and heterogeneous populations. Health literacy was assessed using the HLS19-Q12 instrument and analyzed in SPSS (version 27). Analyses comprised descriptive statistics and binary logistic regression modelling. Statistical significance was set at p < 0.05, with adjusted odds ratios (AORs) and 95% confidence intervals (CIs) reported. Health literacy was predominantly low, with 62.6% of respondents reporting inadequate literacy, while 37.4% demonstrated sufficient literacy. In the multivariable binary logistic regression analyses, sufficient health literacy was significantly associated with formal employment (AOR = 4.05, p < 0.001, CI: 2.21-7.42), ease of healthcare access (AOR = 2.52, p < 0.01, CI: 1.47-4.34) and language proficiency particularly in Akan/Twi (AOR = 3.49, p < 0.01, CI: 1.43-8.48), Ga/Dangme (AOR = 4.76, p < 0.001, CI: 1.61-14.13), and Gonja/Dagbani (AOR = 4.28, p < 0.001, CI: 1.63-11.21). Other factors including social network, place of residence, health information sources, age, and access to basic amenities equally demonstrated significant associations but with comparatively modest effects. These findings suggest that health literacy among mobile and documentation-insecure populations in Ghana is structured less by demographic factors than by structural and intermediary conditions. While employment, language proficiency, and healthcare access are key determinants, other factors also contribute. Effective interventions therefore require coordinated policy responses that move beyond individual barriers and group identity to address these intersecting constraints that condition access to enabling resources.
Advances in our understanding of hormone action and disease pathophysiology are enabling increasingly personalised therapeutic strategies and expanding treatment options for common endocrine and metabolic disorders, which are major contributors to the global burden of chronic disease.This Review highlights three topics of particular relevance to clinical practice in internal medicine and summarises key developments over the past year.The most rapid progress has been made in the field of obesity, where incretin-based therapies are fundamentally reshaping clinical management. Beyond achieving substantial and sustained weight loss, these agents offer new opportunities to prevent and treat a broad range of obesity-related complications. At the same time, emerging diagnostic frameworks that move beyond the traditional body mass index (BMI)-based classification are prompting a reassessment of how obesity is defined and clinically stratified, with the aim of improving risk assessment and guiding treatment decisions.Recent evidence has also refined the diagnostic evaluation and management of adrenal incidentalomas and endocrine causes of hypertension. In parallel, the development of selective aldosterone synthase inhibitors introduces a potential new treatment option for primary aldosteronism, the most common cause of secondary hypertension.A similar paradigm shift is occurring in the management of thyroid nodules and thyroid cancer. Contemporary strategies increasingly emphasise risk-adapted diagnostic and therapeutic approaches that enable accurate identification of clinically significant disease while reducing overdiagnosis and unnecessary intervention. In patients with low-risk thyroid cancer, organ-preserving surgery, more selective use of radioiodine therapy, and, in carefully selected cases, active surveillance are increasingly incorporated into clinical practice. Collectively, these developments aim to reduce treatment-related morbidity while maintaining excellent oncological outcomes and preserving long-term quality of life. Neue Erkenntnisse zur Hormonwirkung und Krankheitsentstehung ermöglichen zunehmend individualisierte Therapiestrategien und erweitern die Behandlungsmöglichkeiten bei häufigen endokrinen und metabolischen Erkrankungen, die zu den zentralen Treibern der großen Volkskrankheiten zählen.Der vorliegende Beitrag beleuchtet exemplarisch drei für die internistische Praxis besonders relevante Themenbereiche und fasst die wichtigsten Entwicklungen des vergangenen Jahres zusammen. Besonders dynamisch ist der Erkenntnisgewinn im Bereich der Adipositas, deren Behandlung durch moderne inkretinbasierte Medikamente derzeit einen grundlegenden Wandel erfährt. Diese Therapien eröffnen nicht nur neue Perspektiven für eine effektive Gewichtsreduktion, sondern auch für die Prävention und Behandlung zahlreicher adipositasassoziierter Begleiterkrankungen. Gleichzeitig rücken neue diagnostische Konzepte in den Fokus, die über die klassische BMI(„body-mass index“)-basierte Einteilung hinausgehen und eine differenziertere klinische Risikostratifizierung dieser chronisch progredienten Erkrankung ermöglichen sollen.Auch bei Nebennierenraumforderungen und hormonell bedingten Hypertonieursachen tragen aktuelle Erkenntnisse zu einer präziseren Diagnostik und einem gezielteren Management bei. Darüber hinaus eröffnen selektive Aldosteron-Synthase-Inhibitoren neue therapeutische Optionen für den primären Hyperaldosteronismus, die häufigste Ursache einer sekundären Hypertonie.Ebenso zeichnet sich bei Schilddrüsenknoten und Schilddrüsenmalignomen ein Paradigmenwechsel ab. Im Mittelpunkt stehen risikoadaptierte diagnostische und therapeutische Strategien, die eine zuverlässige Identifikation klinisch relevanter Befunde ermöglichen und gleichzeitig Überdiagnostik sowie unnötige Therapien vermeiden sollen. Insbesondere beim Niedrigrisiko-Schilddrüsenkarzinom gewinnen organerhaltende Operationsverfahren, die selektivere Anwendung der Radiojodtherapie und in ausgewählten Fällen sogar aktive Überwachungsstrategien zunehmend an Bedeutung. Ziel dieser Entwicklungen ist es, bei unverändert hoher onkologischer Sicherheit die therapiebedingte Morbidität zu reduzieren und die Lebensqualität der Betroffenen langfristig zu erhalten.
Under China's county medical consortium system, this study explores how level of care integration and other key attributes of medical institutions influence patients' healthcare choices and examines differences in preferences among population subgroups. This study constructed a virtual medical institution choice set using a discrete choice experiment (DCE) with eight institutional attributes. A total of 676 respondents were recruited via an online convenience sample on the Credamo platform using a self-developed questionnaire. The conditional logit model and fixed effects model were adopted to analyze 10,816 valid observations. Medical quality emerges as the primary factor influencing patients' healthcare choices, followed by the level of care integration. Heterogeneity analysis reveals that rural residents and individuals with lower educational attainment prioritize practical factors such as convenience and medical costs. Individuals with higher education levels and female patients demonstrate greater concern for medical care quality. All findings reflect stated preferences in hypothetical scenarios rather than observed healthcare-seeking behavior. Within this stated-preference framework, higher levels of integrated care, streamlined referral procedures and higher levels of information sharing were consistently associated with stronger patient choice. Importantly, we make no causal claim that these preferences directly predict real-world care-seeking or system-level outcomes. To move from stated preference to observed behavior, future research combining offline representative sampling with real utilization data is needed to validate and extend these patterns.
Epithelial-mesenchymal transition (EMT) is a flexible cell-state program that supports tumor invasion, metastasis, immune escape, and therapy resistance. It is not a simple switch from an epithelial to a mesenchymal phenotype. Instead, cancer cells often move through intermediate or partial EMT states, which allow them to retain cell-cell adhesion while gaining motility and stress tolerance. Recent studies show that RNA modifications, including N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), A-to-I RNA editing, pseudouridine (Ψ), N4-acetylcytidine (ac4C), and N7-methylguanosine (m7G), add an important post-transcriptional layer to EMT regulation. These modifications control RNA stability, translation, splicing, export, and innate immune sensing. They therefore connect environmental cues, such as hypoxia, TGF-β signaling, inflammatory cytokines, and therapeutic stress, to EMT-related gene expression programs. This review summarizes how major RNA modification systems regulate EMT in cancer. Rather than listing individual findings, we compare common regulatory patterns across tumor types. m6A has the strongest evidence base and acts through writer-reader-eraser modules that regulate EMT transcription factors and signaling pathways such as TGF-β/SMAD, Wnt/β-catenin, PI3K/AKT, EGFR/STAT3, and Notch. m5C and ac4C mainly promote EMT by stabilizing transcripts and enhancing translation, whereas m7G influences EMT through translational reprogramming and codon-biased protein synthesis. A-to-I editing has more complex effects because it can either support immune evasion and plasticity or generate tumor-suppressive RNA isoforms. Ψ-related mechanisms remain less developed, but early evidence suggests roles in RNA stability, stress adaptation, and invasive behavior. We also discuss how EMT and RNA modifications interact with the tumor microenvironment, especially immune suppression and checkpoint resistance. Finally, we evaluate therapeutic opportunities and key challenges. Current studies are limited by reliance on bulk assays, incomplete site-specific validation, weak causal evidence, and insufficient clinical standardization. Future work should integrate single-cell and spatial epitranscriptomics, functional RNA editing tools, and clinical cohorts to define which RNA modification events are true drivers of EMT and which are only associated markers.
This study investigates the heterogeneity of tuberculosis (TB) treatment outcomes across 75 countries by applying quantile regression modeling to a comprehensive multimodal dataset from Kaggle, encompassing socioeconomic, demographic, and comorbidity factors collected annually. Our objective is to move beyond average-centric analyses and characterize the full conditional distribution of TB incidence and treatment success, thereby revealing critical determinants at both high- and low-risk extremes. By integrating features such as HIV prevalence, GDP, healthcare expenditure, and comorbidity rates, the quantile regression framework facilitates nuanced risk stratification, uncovering complex interactions between predictors and outcome variability. Model evaluation using mean absolute error, R-squared, and quantile loss confirms robust predictive performance and enhanced interpretability relative to traditional linear regression approaches. Key findings highlight the outsized influence of HIV prevalence and healthcare spending on unfavorable TB quantiles, while favorable outcomes correlate more strongly with higher GDP and expanded health infrastructure. These insights provide actionable guidance for policymakers and global health stakeholders seeking to allocate resources efficiently and design targeted interventions for diverse epidemiological profiles. The primary contribution of this work is a statistically rigorous, distribution-aware approach for evaluating and explaining multinational TB prognoses, advancing both methodological and practical understanding of global TB disparities.
Rural communities face widening mortality gaps driven less by geography than by policy choices shaping care delivery, workforce distribution, and investment. Informed by the 2025 Dartmouth Rural Health Symposium, this article synthesizes evidence and field experience to outline a practical reform agenda. The authors propose redefining rural hospitals around essential, financially viable services; scaling team-based and artificial intelligence-supported care; modernizing payment models; and rebuilding trust through community partnership. A phased implementation plan proposes near- and long-term actions and highlights responsibilities across sectors. Durable progress will depend on aligning incentives with prevention and local relevance, allowing proven innovations to move from isolated pilots to routine practice nationwide.
The global discourse surrounding menopause has undergone a seismic shift, transitioning from clinical silence to a hyper-visible cultural phenomenon. However, this "menopausal turn" has introduced a significant paradox: while visibility reduces stigma, it frequently replaces clinical nuance with market-driven, reductive narratives. This paper provides a comprehensive bio-psycho-social synthesis of the menopause transition, bridging the gap between emerging neurobiological evidence and contemporary public discourse. We examine the neuroendocrine basis of perimenopausal mood changes, illustrating how fluctuating ovarian steroids - specifically oestradiol and progesterone - modulate serotonergic, dopaminergic, and GABAergic systems to create a window of psychiatric vulnerability. Challenging the "oestrogen deficiency" monocausal model, we integrate epidemiological data from major longitudinal cohorts, such as the Study of Women's Health Across the Nation, to highlight the "domino effect" of vasomotor symptoms, sleep fragmentation, and pre-existing psychosocial stressors. A critical focus is placed on the diagnostic attribution bias prevalent across medical specialties. We argue that primary care and psychiatry often operate through divergent "disciplinary lenses," leading to the misattribution of symptoms and fragmented care pathways. Furthermore, we critique the commercialisation of the "wellness" industry, which often leverages "femvertising" to promote non-clinical solutions that mask complex neurobiological realities. Ultimately, this paper advocates for a nuanced, interdisciplinary framework. By reconciling physiological evidence with the lived sociocultural experience, healthcare providers can move beyond superficial public narratives to deliver individualized, evidence-based care that addresses the holistic mental and physical wellbeing of women navigating this profound midlife transition.