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Distal femoral fractures constitute a significant proportion of all femoral fractures and are increasingly common due to the aging population and high-energy trauma in younger individuals. Surgical management is preferred for most cases, with the two predominant modalities being distal femoral locking plates (DFLP) and retrograde intramedullary nailing (RIMN). The choice between plating and nailing remains controversial, with ongoing debate regarding optimal treatment strategies based on fracture characteristics, patient factors, and surgeon preference. The primary objective of this study was to compare the time to radiographic fracture consolidation between patients treated with DFLP fixation and those treated with RIMN. Secondary objectives included comparison of functional outcomes at six months, as measured by the Knee Society Score (KSS), overall union rates, including delayed union and nonunion, and complication profiles, encompassing surgical site infection, implant failure, and postoperative malalignment. A retrospective cross-sectional study was conducted between November 1, 2023, and October 31, 2025, including 46 samples. The key outcome measures included operative time, union rate, time to union, functional scores (KSS), infection rate, malalignment, and implant failure. Plating showed slightly higher nonunion and delayed union rates, especially in cases with poor soft tissue or comminution. Measured by KSS, both groups demonstrated comparable long-term functional outcomes. Plating had higher superficial infection rates due to wider exposure. RIMN showed higher malalignment, often valgus, due to technical limitations during reduction. There is no definitive superiority between distal femur plating and nailing. Both yield excellent outcomes when applied judiciously. DFLP is preferred in intra-articular, osteoporotic, and comminuted fractures. RIMN is ideal for simple, extra-articular fractures and for younger patients. Surgeon familiarity and patient-specific factors remain pivotal in decision-making.

Atrophic non-union is a significant clinical challenge associated with impaired early inflammation resolution and delayed osteogenesis. Although the osteoimmune microenvironment is critical for bone healing, the specific molecular mechanisms regulating this process require further elucidation. We utilized a 6-mm critical-size rat femoral defect model and time-series RNA sequencing to explore potential molecular mechanisms. Additionally, primary mouse bone marrow-derived macrophages (BMMs) were used for in vitro validation of in vivo findings. Histological and transcriptomic analyses identified 1-2 weeks post-fracture as a critical window characterized by significant inhibition of the canonical BMP9-SMAD signaling cascade in the non-union microenvironment. In vivo, this defect was associated with sustained accumulation of M1 macrophages, impaired reparative M2 polarization, and osteoclast-mediated bone resorption. In vitro studies further validated the in vivo results, confirming that BMP9 promotes M2 macrophage polarization, upregulates chemokines Ccl2 and Ccl7, and inhibits RANKL-induced osteoclastogenesis through the canonical SMAD-ID1 pathway. Early loss of canonical BMP9-SMAD signaling disrupts the balance between immune cell recruitment and bone remodeling, contributing to the development of atrophic non-union in critical-size defects. Targeted modulation of the BMP9-driven osteoimmune axis may offer a potential therapeutic strategy for impaired bone healing.

Although triple therapy has been recommended as foundational therapy for heart failure with preserved ejection fraction (HFpEF), residual risk remains high in affected patients. The efficacy of beta-blockers in HFpEF remains controversial. This single-center retrospective cohort study included 600 patients with HFpEF who received triple therapy (as defined per the study protocol) at Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, between January 2018 and January 2025. A 1:1 propensity score matching (PSM) approach was used to balance baseline confounding factors. The efficacy and safety of quadruple therapy were compared with those of triple therapy alone. The primary endpoint was the composite of heart failure hospitalization or cardiovascular death. After PSM, 360 patients were matched, with 180 patients in each group. During a median follow-up of 37.8 months, the incidence of the primary endpoint was significantly lower in the quadruple therapy group than in the triple therapy group [17.8% vs. 25.0%, hazard ratio (HR) = 0.678, 95% confidence interval (CI): 0.432-0.967, P = 0.035]. The quadruple therapy group had significantly lower rates of first heart failure hospitalization (14.4% vs. 20.6%, HR = 0.672, P = 0.030) and recurrent heart failure hospitalization (0.217 vs. 0.325 events per person-year, HR = 0.654, P = 0.015). Subgroup analyses showed that patients with concomitant coronary artery disease (HR = 0.591, P = 0.047) and baseline heart rate ≥70 beats per min (HR = 0.572, P = 0.045) derived greater benefit from quadruple therapy. A trend toward benefit was observed in patients with baseline LVEF of 50%-59%, but no significant interaction was detected. The overall safety profiles were comparable between the two groups. In this real-world observational cohort of patients with HFpEF receiving triple therapy, quadruple therapy was associated with a lower risk of the composite of heart failure hospitalization or cardiovascular death, driven primarily by a reduction in heart failure hospitalizations. No statistically significant difference in cardiovascular or all-cause mortality was observed. The association appeared more prominent in patients with concomitant coronary artery disease and higher baseline heart rate in exploratory subgroup analyses. Given the observational design, these hypothesis-generating findings cannot establish causality and require prospective validation.

This review compares the outcomes of total ankle replacement (TAR) and ankle fusion (AF) in patients with end-stage ankle osteoarthritis (OA) based on recent comparative studies (1 January 2023 to 31 December 2025). Racial/ethnic, socioeconomic, and payer status disparities have been reported in the likelihood of experiencing TAR versus AF for ankle OA. A prospective multicentre study with level II evidence found that the long-term clinical results of TAR and AF were similar. A meta-analysis identified TAR as the superior intervention, demonstrating significant advantages in patient-reported outcome measures. Three systematic reviews have reached the following conclusions: i) postoperative outcomes are similar in TAR and AF; ii) TAR and AF have similar complication rates (both minor and major); iii) both TAR and AF are safe and effective surgical treatments for ankle OA; besides, TAR had notable lower total complications, implant removals, adjacent level fusion surgeries, and non-union/open reduction and internal fixation surgeries after the index procedure. The existence of mixed evidence found in the literature makes it necessary to select the surgical technique to be used (TAR or AF) on an individual basis. To definitively determine which procedure is more appropriate in advanced ankle OA, more and better-designed studies are required, given that the results reported thus far do not permit to determine with absolute certainty which of the two procedures, TAR or AF, is more adequate.

Information on the safety profile of antidiabetic medications is essential for informed treatment decisions in type 2 diabetes mellitus. Although this information is available in regulatory documents of individual drugs, a comprehensive overview across all approved antidiabetics is lacking. Such an overview is important for clinicians and regulators to compare safety profiles across antidiabetics and to understand how safety information evolves over time. Safety information for 27 first-in-class antidiabetics approved in the European Union (1995-2024) was extracted from the summary of product characteristics (SmPCs) and three clinical practice guidelines (CPGs: European Association for the Study of Diabetes, American Diabetes Association and National Institute for Health and Care Excellence). We assessed changes in safety outcomes over time, with these classified using the Medical Dictionary for Regulatory Activities (preferred term [PT] level). A total of 326 unique safety outcomes were identified, with 63 of these also reported in CPGs. The number of safety outcomes increased post-marketing for most classes, notably in SGLT-2 inhibitors (+21 PTs) and GLP-1 RAs (+18 PTs). Hypoglycaemia (96%) and skin reactions (e.g., 59.3% rash) were commonly reported. Less frequent outcomes included genital infections (SGLT-2i) and acute haemolytic anaemia (sulfonylureas). Severe but rare outcomes such as Stevens-Johnson syndrome (DPP-4 inhibitors) and Fournier's gangrene (SGLT-2 inhibitors) were added post-marketing. The safety profile of antidiabetics is similar, with small divergence including some serious safety outcomes, and has expanded over time by approximately one-third. On the contrary, CPGs incorporated only a few safety outcomes, reflecting their distinctive different role in clinical practice.

Emergency medical services (EMS) staff worldwide have long been at risk of encountering violence and aggression (V&A) at work, including threats, verbal, physical and sexual assault, and on rare occasions, fatalities occur. Exposure to V&A can result in stress, fear and burnout. This is an international problem and EMS employers, trade unions and others are working towards tackling it. The aim of this research was to conduct an exploratory qualitative interview study of EMS staff focusing on experiences, perceptions and interpretations of V&A directed towards them. This study took place in 2022 in one UK ambulance service covering a population of three million people. Individual, one-to-one semi-structured interviews were conducted with EMS staff via a Voice over Internet Protocol. Data were thematically analysed drawing on evolved grounded theory methodology concepts. 10 EMS staff were interviewed, and the following categories emerged: Rusted, busted and inevitability of V&A in EMS environment, Tolerable or intolerable V&A in EMS, Gendered V&A and genderisation in EMS, Modifiable factors and harm reduction of V&A in EMS, Professional, ethical and clinical judgments of V&A in EMS and Sociocultural and system frustrations of V&A in EMS. The basic social process that emerged was one of Systemic frustration and gender-based V&A in EMS. Protecting EMS staff from V&A is complex and multifaceted, and we have conducted a thematic analysis drawing on evolved grounded theory concepts that proposes V&A in EMS may be borne out of, and sustained, by systemic frustration and gender-based issues. We draw on Dollard's et al (1939) frustration-aggression hypothesis and Kelly's 'Continuum of Violence' (1988). Experiences of sexual V&A revealed in our study, supported by a wider body of knowledge, lay bare a caring context of rampant gender-based V&A directed towards EMS staff by members of society, colleagues and within the context of a patriarchal EMS. Our study revealed how EMS has not effectively tackled V&A and the many sociocultural constructs within EMS. We advocate for purposeful efforts, further research and systemic interventions beyond punitive measures to tackle this issue.

BACKGROUND Supracondylar humerus fractures are the most common elbow fractures in children and are frequently treated with closed reduction and percutaneous pinning when displaced. Because this procedure relies heavily on intraoperative fluoroscopy, surgical setup can influence operative time, radiation exposure, and workflow efficiency. However, comparative evidence on different fluoroscopic positioning strategies and antisepsis protocols remains limited. This retrospective, non-randomized study was designed to compare a conventional technique with a modified fluoroscopic approach in pediatric Gartland type II supracondylar humerus fractures. MATERIAL AND METHODS This retrospective, non-randomized comparative study included 91 children aged 1 to 13 years with Gartland type II supracondylar humerus fractures treated between 2019 and 2023. Patients were divided into 2 groups according to the surgical method: conventional method (CM, n=49) and modified method (MM, n=42). Demographic data, operative duration, fluoroscopy exposure, preparation time, radiological alignment, pin removal timing, complications, and Mayo Elbow Performance Scores were compared. RESULTS There were no significant differences in age, sex distribution, or radiographic alignment between the groups. The MM group had significantly shorter operative time, preparation time, and fluoroscopy duration. No infections or neurovascular complications were observed. Functional outcomes and fracture union were similar in both groups. CONCLUSIONS The modified technique appears to be a safe and efficient alternative to the conventional method, providing shorter operative and fluoroscopy times while maintaining comparable early clinical and radiological outcomes.

Dyslipidemia, characterized by abnormal lipid levels including low high-density lipoprotein cholesterol (HDL-C), high triglycerides, and elevated low-density lipoprotein cholesterol&#xa0;(LDL-C)&#xa0;or total cholesterol (TC), poses a significant cardiovascular threat in India amid rapid urbanization and lifestyle shifts. To assess the prevalence of various components of dyslipidemia in India using data from the large, nationally representative, Indian Council of Medical Research-India Diabetes&#xa0;(ICMR-INDIAB) study. The ICMR-INDIAB study employed a stratified multistage cluster sampling design across representative urban and rural clusters in all Indian states and union territories, targeting adults (n&#xa0;=&#xa0;121,078) aged &#x2265;20 years. In every 5th participant (23,665-urban: 7026 and rural: 16,636), fasting venous blood samples were analyzed for lipids using standardized enzymatic methods. Dyslipidemia was defined using the Lipid Association of India&#xa0;guidelines [high TC &#x2265;200&#xa0;mg/dL, high triglycerides &#x2265;150&#xa0;mg/dL, high LDL-C &#x2265;100&#xa0;mg/dL, and low HDL-C (<40&#xa0;mg/dL men, <50&#xa0;mg/dL women)]. Generalized obesity was defined as BMI &#x2265;25&#xa0;kg/m&#xb2; (World Health Organization Asia Pacific guidelines). The overall weighted prevalence of dyslipidemia was 87.3%, significantly higher in urban areas and among females. The burden of dyslipidemia in India was predominantly driven by low HDL-C (66.8%). Dyslipidemia prevalence increased with worsening glycemic status, rising body mass index (BMI), and the presence of hypertension; it was also present in 40% of individuals without diabetes, hypertension, or obesity.&#xa0;Younger age, female sex, sedentary lifestyle, obesity, hypertension, and diabetes were associated with dyslipidemia. Dyslipidemia is highly prevalent among Indian adults, especially at younger ages and among those with adverse glycemic status, obesity, and hypertension. However, there is a substantial burden of dyslipidemia among metabolically normal individuals, highlighting the need for broader lipid screening strategies and early preventive interventions to curb the rising trend of cardiovascular disease risk in India.

The recognition and positioning of characters on the water gauge are important components of artificial intelligence system for reading ship draft weighing. Meanwhile, the manual annotation of oriented objects has a large workload and low accuracy. To address these issues, this paper proposes a novel oriented detection framework. It introduces three additional parameters to refine the horizontally detected bounding boxes from the model and employs two symmetric functions to confine the angles and scales within specified ranges. In the training and testing of the model, only the horizontal annotation information of the object is needed, reducing the workload of annotation of the target in the dataset. A residual network has been added to the backbone of object detector(YOLO) to enhance the feature extraction capability of deep modules and improve the sensitivity to small objects. For more accurate oriented estimation, we utilize improved Intersection over Union(IoU) to the bounding box regression loss.This method is particularly effective for objects with a dominant orientation and approximately rectangular shapes, such as the characters, vehicles, and buildings commonly found in aerial imagery. A simple implementation of our method has achieved state-of-the-art performances on aerial objects datasets, with a negligible reduction to detection speed. After applying the novel oriented detection method to the intelligent system, real-time testing was conducted on 120 drone videos, resulting in a 35.3% improvement in the accuracy of the system's water gauge readings.

Lymph nodes (LNs) in medical images often have fuzzy boundaries, vary in size and shape, and have intensities similar to those of neighboring tissues, making accurate segmentation challenging. To address this issue, we propose a multi-scale attention-enhanced network (MSA U-Net) that integrates channel-wise and spatial attention mechanisms for automatic segmentation of metastatic pelvic LNs associated with uterine malignancies from sagittal magnetic resonance imaging (MRI). This network integrates a U-Net backbone, fuses features from different encoder levels at skip connections, and feeds the fused features into the decoder at each layer. Different receptive fields are used at the bottleneck nodes to capture multiscale contextual information. A detection head is added to the bottom layer of the network and the detection results are used to assist in the final segmentation of the image. A lightweight design of the convolutional block attention module is also implemented to optimize feature representation. The experimental results demonstrate that the proposed network achieves better segmentation performance compared to the baseline model. The proposed network achieves a mean intersection over union of 0.76, an average pixel accuracy of 0.97, a precision of 0.78, a recall of 0.97, a Dice coefficient of 0.82, and a Hausdorff distance of 2.21. The proposed MSA U-Net segmentation network effectively segments LNs in uterine MRI images, outperforming existing segmentation methods. This study provides a reliable and automated method to help clinicians detect LN, thus improving clinical decision-making.

Capacity management plays an increasingly important role in healthcare delivery, both at national and supranational level, in increasing value for money. In this paper, we propose using cross-border patient mobility across European Union (EU) countries to pool demand and reduce excess capacity. In a setting where the number of patients requiring a specific treatment is fixed but the facility requires a fixed capacity that cannot be adapted to demand, we show that cross-border patient mobility may improve welfare. From a legal perspective, we demonstrate that such mobility is compatible with existing EU law (comprising both EU primary and secondary law, namely the Patient Mobility Directive and the Social Security Coordination Regulation) and the case law of the European Court of Justice. These judgments confirm that planning and cost control objectives may justify not only restricting but also encouraging patient mobility, provided non-discrimination and proportionality are respected. In conclusion, this paper offers interdisciplinary solutions for reconciling patients' preferences with member states' planning goals, showing that cross-border healthcare cooperation can enhance efficiency, equity, and solidarity within the current EU legal framework.

Critical care research focuses on life-threatening conditions such as sepsis, trauma, hemorrhage, and burn injury, which account for millions of hospitalizations and hundreds of thousands of deaths annually in the United States alone. Recent policy initiatives by the U.S. Food and Drug Administration (FDA) and the National Institutes of Health (NIH) have promoted New Approach Methodologies (NAMs), including organoids, organ-on-chip platforms, and computational models, as alternatives to animal research. While NAMs offer valuable tools for mechanistic investigation and screening applications, this review examines whether current NAM technologies can adequately replace animal models in critical care research. Critical illness involves the whole organism, including dynamic organ-organ interactions, immune-microbiome crosstalk, and adaptive systemic feedback loops. By examining major domains in critical care research and targeted organ injuries, it becomes clear that while NAMs excel at interrogating isolated subsystems, they cannot currently replicate integrated physiological responses. Animal models remain essential for questions requiring assessment of multi-organ dysfunction, therapeutic safety evaluation, and clinically relevant disease trajectories. Premature policy shifts away from animal research will impede advances in critical care medicine. This review proposes a "methodological pluralism" approach that integrates NAMs with appropriately designed animal studies through harmonized endpoints and reverse-translation frameworks. Recommendations include continued refinement of animal models to better represent the heterogeneity of human populations, adoption of quality standards for preclinical research, and strategic deployment of both NAMs and animal models based on fit-for-purpose criteria. We believe this approach will satisfy ethical considerations, scientific rigor, and public health needs in critical care research.

Urolithin A (UA) is a gut microbiota-derived metabolite formed from dietary ellagitannins and ellagic acid. It has drawn sustained interest because it can influence mitochondrial quality control, but the evidence does not support a simple anti-aging or anticancer label. In this review, UA is examined across microbial metabolism, urolithin metabotypes, pharmacokinetic exposure, mitophagy biology, aging-related phenotypes, and cancer. The emphasis is placed on what has been shown, what remains model-dependent, and where translational claims are still premature. Preclinical work links UA to PINK1/Parkin-, TFEB-, AMPK-, sirtuin-, and Nrf2-associated pathways, with reported improvements in mitochondrial turnover and inflammatory signaling. Human data are narrower: most trials have been short and have focused on safety, muscle performance, mitochondrial signatures, and circulating biomarkers. Evidence for cancer prevention or cancer therapy still comes mainly from cell and animal studies. Because mitophagy can limit early mitochondrial damage but may also help established tumors survive hypoxia, nutrient restriction, dormancy, and therapy-induced stress, UA is better regarded as a microbiome-dependent mitochondrial modulator whose effects depend on biological setting. The next step is to define direct molecular targets, test native and conjugated UA at human-relevant exposure ranges, account for UM-A, UM-B, and UM-0 metabotypes, and evaluate cancer-specific endpoints before making therapeutic claims.

Two mRNA vaccines (V1 and V2) from our previous study, encoding different CHIKV structural proteins, exhibit distinct immune effects and protective efficacy. However, the immune mechanisms underlying these differences remain unclear. In this study, we use an integrated multi-omics approach (single-cell RNA sequencing, immune repertoire sequencing, and Olink cytokine profiling) to elucidate the differential immune cell activation states induced by the two vaccines and the potential structural basis of the antigens that may account for these differences. We find that V2 induces sustained B cell activation, predominantly IgG-type memory antibodies, and a robust recall response following viral challenge. By contrast, V1 elicits only transient B cell activation and relatively weak T cell responses. These findings delineate a mechanistic pathway linking mRNA antigen structure to immune activation, functional differentiation, immunological memory, and protective efficacy. This work enhances our understanding of the immunological mechanisms underlying CHIKV mRNA vaccination and offers insights for rational vaccine antigen design.

We present a high-speed force microscopy platform mounted on a confocal microscope with a z sample stage enabling long-range, high-speed force spectroscopy measurements on biological samples. The control software is built on a field-programmable gate array&#xa0;(FPGA)-based data acquisition and processing system, complemented with a custom graphical user insterface (GUI). We introduce smart algorithms based on probe-engagement prediction algorithms that leverage previously measured probe-sample contact to accelerate the probe engagement to mm/s and decelerate it in proximity of contact to user-defined &#x3bc;m/s velocities. This significantly reduces long-range force curve acquisition time and data density. Using this system, we provide proof-of-concept mechanical maps of cell clusters to extract topography and viscoelastic parameters. To further explore the versatility of our system, we probed the forces required to extract membrane tethers from monocytic cells using ultrashort cantilevers functionalised with adhesion molecules. Our system allowed us to cover retract velocities from ~1&#x2009;&#x3bc;m/s up to ~6000&#x2009;&#x3bc;m/s, and to explore the dynamics of tether formation at physiologically relevant velocities. Our results show that coupling extended z displacement with the prediction-based engagement algorithms enables rapid, quantitative mechanical mapping of heterogeneous biological samples with large topography variation and supports measurements requiring long distances at high velocities.

Malnutrition is highly prevalent among hospitalized older adults and is associated with adverse clinical outcomes. However, the determinants of nutritional improvement and clinical implications of such improvement in oldest-old hospitalized patients remain insufficiently characterized. This study aimed to identify factors associated with nutritional improvement and to evaluate the relationship between this improvement and clinical outcomes among hospitalized patients aged &#x2265;80&#x202f;years who were at nutritional risk. This multicenter prospective cohort study included hospitalized patients aged &#x2265; 80&#x202f;years at nutritional risk (Nutritional Risk Screening 2002 score &#x2265; 3) from geriatric wards of tertiary hospitals in China. Nutritional status was assessed using the Mini Nutritional Assessment-Short Form (MNA-SF) at admission and at 90-day follow-up. Nutritional improvement was defined as an improvement in MNA-SF category at 90&#x202f;days. Multivariable logistic regression analyses were performed to identify factors associated with nutritional improvement and to examine the association between nutritional improvement and adverse clinical outcomes, including mortality, readmission, falls, and infection. Among 675 patients included in the final analysis (mean age 88.5&#x202f;&#xb1;&#x202f;4.8&#x202f;years; 63.7% male), 251 (37.2%) achieved nutritional improvement at 90&#x202f;days. In multivariable analyses, a higher Charlson Comorbidity Index was associated with a lower likelihood of nutritional improvement (odds ratio [OR]&#x202f;=&#x202f;0.751, 95% confidence interval [CI]: 0.665-0.849, p&#x202f;<&#x202f;0.001). Achieving energy adequacy (OR&#x202f;=&#x202f;2.424, 95% CI: 1.511-3.887, p&#x202f;<&#x202f;0.001) and good adherence to nutritional interventions (OR&#x202f;=&#x202f;1.921, 95% CI: 1.303-2.834, p&#x202f;<&#x202f;0.001) were independently associated with nutritional improvement, whereas protein adequacy was not. Nutritional improvement was independently associated with reduced risks of readmission (OR&#x202f;=&#x202f;0.545, 95% CI: 0.351-0.847, p&#x202f;=&#x202f;0.007) and new infection (OR&#x202f;=&#x202f;0.388, 95% CI: 0.225-0.671, p&#x202f;<&#x202f;0.001) but was not significantly associated with mortality or falls. Among hospitalized oldest-old patients at nutritional risk, achieving adequate energy intake and maintaining adherence to nutritional interventions were independently associated with nutritional improvement. Nutritional improvement was associated with lower risks of readmission and infection. These findings highlight the potential clinical relevance of sustained nutritional monitoring and management in oldest-old hospitalized populations.

Culturability remains the predominant method for assessing bacterial viability in tuberculosis research and clinical practice. However, growth-based detection provides only a limited and context-dependent dimension of Mycobacterium tuberculosis (MTB) survival. MTB populations may evade recovery by standard culture while retaining molecular, metabolic, or functional features inconsistent with irreversible cellular death, resulting in persistent discrepancies between culture outcomes and other biological or clinical indicators. This review explores viable but non-culturable (VBNC)-like phenotypes and differentially culturable tubercle bacilli (DCTB) as detection-defined frameworks for interpreting such growth-invisible populations. We analyze their methodological foundations and interpretative limitations, emphasizing that neither reflects a discrete or stable physiological state. Integrating evidence from resuscitation assays, molecular viability measurements, and clinical observations, we propose a continuum-based interpretation of MTB viability in which bacterial populations occupy diverse physiological states spanning survival potential and growth competence. Within this framework, apparent non-culturability is more accurately conceptualized as a conditional result of physiological limitations and methodological sensitivity, rather than as conclusive evidence of bacterial death or dormancy. This perspective provides a coherent conceptual foundation for interpreting bacterial persistence, clearance, and treatment response in tuberculosis.