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Outbreak investigations of two carbapenemase-producing bacteria (CPB)-clusters identified a link to utility room wastewater drains (URWD), prompting an investigation into CPB-colonization of the hospital's URWD and into utility room management to identify possible breaches in infection prevention and control (IPC) measures. At the University Hospital Basel, Switzerland, a cluster of four patients with VIM-1-producing Enterobacter hormaechei and two patients with KPC-3-producing Citrobacter freundii, occurred between 07/2022 - 07/2024. A multidisciplinary team (IPC specialists, nurses, cleaning experts) evaluated utility room management. Wastewater drains in affected patient rooms and 25 utility rooms of the hospital building (including two wards in which the two transmission-cluster occurred) affected by the clusters were screened for CPB-colonization and whole genome sequencing was performed on clinical and environmental CPB isolates. The blaVIM-1 and the blaKPC-3 gene corresponding to both clusters were identified in sequences of Citrobacter freundii and Klebsiella pneumoniae isolates colonizing the ward's URWD. Colonized drains were in proximity to affected patient's rooms, while none of the wastewater drains in the respective patient rooms was colonized with CPB. Overall, CPB were identified in 52% of all URWD. Several breaches in utility room management and design facilitating colonization with CPB and potentially leading to contamination of shared medical equipment by dispersal were observed, including lacking separation between clean and contaminated zones in utility rooms (34%), and improper use of contaminated zones for storage of clean shared medical equipment (88.7%). URWD serve as reservoirs for CPB. Breaches in utility room management and design, potentially leading to contamination of shared medical equipment by dispersal from contaminated wastewater drains, represent an intervention target for prevention of CPB-transmission.

HIPAA breaches and unauthorized access to Electronic Health Records (EHRs) have been growing more likely due to the sudden digitalization of the healthcare sector. High endurance, privacy-based security practices have never been more in demand as hospitals and other medical facilities of this type have clung to the electronic system. The given study considers this problem by suggesting an anomaly detection model that determines the presence of abnormal or suspicious access patterns in EHR systems using Variational Autoencoders (VAEs). One of the main weaknesses of creating an efficient security model in the healthcare sector is that access to real-world information is limited and is constrained by privacy policies. To bridge this challenge, a synthetically enriched EHR access log dataset was generated and realistic features, including departmental affiliations, user roles, frequency of access, and timestamps, were ensured; the artificially generated dataset is, therefore, a close simulation of real-world hospital activities. By observing the access patterns of healthcare professionals that are generally typical in a latent space, the proposed VAE model can signal deviations that can indicate a possible security breach or policy violation without revealing or even relying on actual patient data, thus identifying both large and small-scale aberrations by modelling these latent representations. Evidence of the superiority of VAE-based detection over traditional machine learning algorithms, including Isolation Forest and One-Class Support Vector machines, using some key measures, like accuracy (F1-score: 0.93), lower false-positive rates, and greater sensitivity to noisy data, confirms this assertion. As a result, unsupervised deep generative modelling plus synthetic data generation provides a new, privacy-conserving approach to improving the cybersecurity of medical information systems. Based on the results, the VAE-based anomaly detection can become a trusted means of protecting sensitive healthcare infrastructure against the changing cyber risks.

This paper contributes to a broader survivor-led program of research on second violence: the institutional reproduction of harm through systems formally designed to respond to violence. Within that broader program, the paper focuses on one police station encounter to examine how police contact can operate as a modifiable public health exposure in family and domestic violence response. Survivor-led autoethnographic case study. Data were drawn from The Second Violence, a four-year, ethics-approved autoethnographic study documenting lived experience of navigating police and other institutions after separation from an intimate relationship characterised by coercive control and violence. Focusing on a help-seeking episode in which I attended a local police station to report apparent breaches of a Family Violence Intervention Order, I analysed a vignette of this encounter, fieldnotes and analytic memos using feminist autoethnography and Cultural-Historical Activity Theory (CHAT) to examine how objects of work, rules and division of labour shaped safety outcomes. In this case, police contact operated as a second exposure to harm by intensifying psychological distress through disbelief, minimisation and dismissive institutional responses; delaying safety when patterns of coercive control were not recognised or recorded; leaving risk insufficiently addressed when apparent breaches were not enforced; and eroding trust in systems expected to be protective, with consequences for future help-seeking and engagement with services. This case suggests that violence prevention and public health responses should address not only perpetrators and primary incidents, but also institutional arrangements that may amplify or attenuate harm. Conceptualising policing as a modifiable public health exposure can inform trauma- and violence-informed practice, integrated risk assessment and survivor-led co-design of responses in which "do no further harm" is treated as a core outcome of family violence systems.

Robot-assisted and navigation-guided spinal instrumentation technologies have transformed spine surgery by improving precision and intraoperative safety. Despite widespread adoption, their relative performance across perioperative efficiency, radiographic accuracy, and complication profiles remains insufficiently clarified. A systematic search of PubMed, Scopus, Cochrane Library, and Google Scholar was conducted through December 2025. Sixteen comparative studies involving 59,474 patients (robot-assisted&#x2009;=&#x2009;11,059; navigation-guided&#x2009;=&#x2009;48,787) were included. Extracted outcomes included operative time, blood loss, length of stay, radiation exposure, fluoroscopy duration, screw deviation, endplate breach, facet violation, Cobb angle correction, and intra- and postoperative screw revision and complication rates. Pooled effect estimates were calculated for continuous and dichotomous variables. Subgroup analyses were performed according to underlying spinal pathology (degenerative lumbar fusion, thoracolumbar posterior instrumentation, and spinal deformity). Robot-assisted surgery demonstrated significantly shorter fluoroscopy time (MD&#x2009;-&#x2009;3.44&#xa0;s; p&#x2009;=&#x2009;0.03), lower pedicle screw deviation (MD&#x2009;-&#x2009;0.16&#xa0;mm; p&#x2009;=&#x2009;0.003), and fewer intraoperative screw revisions (RR 0.42; p&#x2009;=&#x2009;0.009). Navigation-guided surgery showed lower endplate breach rates (RR 2.32; p&#x2009;=&#x2009;0.007). No significant differences were observed in operative time, blood loss, length of stay, total radiation exposure, facet violation, Cobb angle correction, or overall complication rates (all p&#x2009;>&#x2009;0.05). Subgroup analyses showed overall consistency across pathology types: in degenerative lumbar fusion cohorts, robotic assistance was associated with reduced radiation exposure (MD&#x2009;-&#x2009;5.27 mSv; p&#x2009;<&#x2009;0.001) and fewer intraoperative screw revisions (RR 0.41; p&#x2009;=&#x2009;0.02), whereas in deformity cohorts, navigation-guided techniques demonstrated shorter operative time (MD 11&#xa0;min; p&#x2009;=&#x2009;0.01) and lower radiation exposure (MD 11.42 mSv; p&#x2009;<&#x2009;0.001). Most other outcomes remained comparable across subgroups. Current evidence suggests broadly comparable short-term outcomes between robotic-assisted and navigation-guided spinal surgery. However, while each modality demonstrated selective technical advantages, the overall strength of evidence remains insufficient to support definitive comparative conclusions. High-quality randomized trials are warranted.

Ca2+-dependent repair of plasma membrane breaches is essential for animal cell viability. An initial passive influx of extracellular Ca2+ triggers the formation of a protein plug that rapidly seals breaches. However, the mechanism of extracellular Ca2+ requirement for subsequent repair remains undefined. EHD2 protein stabilizes the plasma membrane caveolae, which sustain membrane repair, and maintains high surface levels of the caveolae-resident Ca2+ channel Orai1. We establish the requirement of both Orai1 and EHD2 for repair of plasma membrane lesions induced by mechanical injury or by a model bacterial pore-forming toxin. We demonstrate rapid EHD2 recruitment and Orai1-mediated Ca2+ entry at plasma membrane sites of localized mechanical stimulus, the latter requiring EHD2 and CAV1. EHD2 and Orai1 are necessary for mechanosensitive YAP/TAZ-TEAD activation and positive feedback for CAV1 expression that promotes membrane repair. Our studies establish EHD2 and Orai1 as novel components of mammalian plasma membrane repair and mechanoadaptation.

Giant cell tumor (GCT) of bone is a benign but locally aggressive neoplasm, most commonly affecting the epiphyseal region of long bones. Involvement of the hand bones is rare and is known to exhibit more aggressive behavior with higher recurrence rates compared to conventional sites. Optimal reconstruction following tumor excision in the hand remains challenging, as, along with the reconstruction of the bone defect, the function of the hand should also be addressed. A 19-year-old right-hand-dominant female presented with a progressively enlarging, painful swelling over the dorsum of the right hand. Radiological evaluation revealed an expansile, lytic lesion involving the ring finger metacarpal with cortical breach. Magnetic resonance imaging showed an aggressive lesion with soft-tissue involvement. Histopathological examination confirmed the diagnosis of GCT of bone. The patient underwent wide excision of the tumor followed by reconstruction using a non-vascularized autologous cortical bone graft from the ulna. GCT of the metacarpal is rare and requires aggressive surgical management due to its high recurrence potential. Non-vascularized ulnar bone graft provides a reliable, simple, and effective reconstructive option following tumor excision.

To investigate which pedicle level and wall were most affected by screw malposition in osteoporotic and non-osteoporotic patients undergoing thoracolumbar stabilization, and to determine whether significant differences existed between the groups. This retrospective study analyzed pedicle screw malpositions and the specific walls involved in thoracolumbar stabilization procedures performed between 2014 and 2025 using the freehand technique with fluoroscopic guidance by the same surgical team. A total of 972 patients were included: those with a T-score &#x2264;-2.5 (osteoporotic group) and those with a T-score > -2.5 (non-osteoporotic group). Indications for surgery included traumatic vertebral fracture, spinal stenosis, recurrent disc herniation, spinal tumor, or spondylolisthesis. All patients underwent preoperative MRI, CT, bone mineral densitometry, and X-rays, as well as postoperative CT and X-rays. Patients with acute decompression without preoperative densitometry and those treated with vertebroplasty/kyphoplasty were excluded. In cases of malposition, postoperative CT scans were used to evaluate superior, inferior, lateral, medial, and anterior cortical breaches, and comparisons were made between groups. Screw malposition rates were significantly higher in osteoporotic patients across all levels, particularly in thoracic vertebrae. The medial pedicle wall was most frequently affected in this group. In osteoporotic patients, transpedicular screw fixation using the freehand technique with fluoroscopic guidance was associated with higher malposition rates, especially involving the medial pedicle wall. These complications may be reduced through greater surgical experience and careful intraoperative technique.

This study examined how job embeddedness (EM) serves as a moderating factor and how organizational identification (OI) functions as a mediator in the relationship between psychological contract breach and intention to leave the organization. This study employed a survey and collected data from 305 respondents in the United States. The findings reveal that psychological contract violation (PCV) is positively associated with turnover intention (TI) and negatively related to organizational identification (OI). Moreover, in the relationship between PCV and TI, EM plays moderating and mediating roles, respectively, in the relationship between PCV and OI plays a mediating role. In terms of its contribution to the literature, this study advances research on the relationship between PCV and TI by validating the mechanism of OI and establishing the boundary condition for EM. This study also offers practical guidelines for mitigating TI by enhancing employees' organizational commitment within routine work environments.

Plastic enables anesthesiology through packaging, syringes, tubing, catheters, endotracheal tubes, and ventilator circuits. Created inexpensively from fossil fuels, plastic is easily sterilized and allows healthcare providers to reliably deliver life-saving therapies. However, a growing body of evidence demonstrates that small, often invisible plastic particles are accumulating in human bodies, with potentially serious health consequences. The perioperative period introduces plastics through two primary exposure routes, intravenous and inhalational, that bypass patients' natural toxin defense mechanisms. Moreover, this occurs during surgery, when there are often intense physiologic stressors. Anesthesia providers also face chronic inhalational plastic exposure in the operating room via masks and ambient plastic particles. Although evidence of direct adverse effects from microplastics on human health is limited, associations with disease are emerging while animal studies have shown harm. There are also indirect implications for human health and well-being of breaching the novel entities (which include plastics) planetary boundary. It therefore falls upon all of us to advocate for both more information and safer alternatives-for the health of both patients and providers.

Drug delivery to the gastrointestinal (GI) tract necessitates overcoming multi-level physiological barriers from organ to cellular levels, which exhibit significant heterogeneity under pathological conditions. Conventional delivery strategies, constrained by single-function capabilities, struggle to achieve cross-scale coordination, severely limiting therapeutic efficacy. Modular design (MD) offers an innovative approach to synergistically breaching multiple barriers by decoupling complex functions into standardized units and enabling intelligent assembly. This review systematically analyzes the characteristics and delivery challenges of each barrier level within the GI tract, establishing a materials library that encompasses functional modules for organ-level regulation, mucosal penetration, cellular delivery, and environmental responsiveness. Utilizing GI inflammation and infection as exemplars, the text goes on to highlight the mechanisms and applications of modular assembly strategies in achieving breakthroughs in organ-mucosa, organ-cell, and full-layer barrier technologies. Additionally, it assesses the challenges and prospects for clinical translation. This paper aims to provide design strategies for developing next-generation intelligent oral delivery systems capable of spatiotemporal programming and dynamic response to the multi-level barriers and pathological microenvironments of the digestive tract. This should drive a paradigm shift towards precise drug delivery within complex physiological settings.

The nuclear envelope protects the host genome, yet many viruses must breach this barrier to access nuclear replication machinery. The nuclear pore complex (NPC), the sole gateway for nucleocytoplasmic transport, is therefore a central target for viral nuclear entry. For decades, the mechanisms by which large viral genomes and subviral assemblies traverse this selective channel remained unclear. This was due to limited accessibility to intact nuclear pores, the NPC's massive architecture, and the transient nature of viral nuclear entry. The advent of cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) has transformed this landscape, enabling visualization of NPC architecture and virus-NPC interactions at unprecedented detail. This review summarizes structural insights into NPC architecture and the strategies viruses employ to enter the nucleus. We examine how viruses engage canonical import pathways involving importins and phenylalanine-glycine-nucleoporins, as well as noncanonical mechanisms by which viral components mimic karyopherin. Finally, we offer perspectives on cryo-EM/cryo-ET capturing viral complexes during the entry process, revealing mechanisms of host-machinery exploitation by viruses.

Targeted microbubbles (MBs) have emerged as pivotal dual-functional agents for molecular ultrasound (US) imaging and US-triggered targeted drug delivery. However, the efficacy of traditional ligand-directed MBs is often compromised by the inherent heterogeneity of tumor receptor expression and physiological barriers. Herein, we report a robust targeting platform based on dibenzocyclooctyne-functionalized MBs (MB-DBCO) that leverages metabolic glycoengineering and bioorthogonal strain-promoted azide-alkyne cycloaddition (SPAAC). This strategy decoupled targeting efficiency from genetic receptor expression by pre-installing azide chemical handles onto the tumor cell surface. Our results demonstrate that MB-DBCO provides a stable "chemical anchor" in both 4T1 tumor cells and vascular endothelial cells, significantly enhancing contrast-enhanced ultrasound (CEUS) sensitivity and tumor cell specificity. Crucially, the synergistic combination of SPAAC-mediated covalent tethering and US cavitation-induced sonoporation breaches the endothelial cell barrier and tumor stromal barriers, driving the deep penetration of the paclitaxel (PTX) payload. In vivo studies showed that the MB-DBCO + US treatment leads to profound tumor regression, extensive vascular depletion, and a significantly prolonged survival time in aggressive 4T1 tumor models. This study establishes a modular, chemically-defined, and scalable targeting platform that overcomes the critical biological barriers of solid tumors, offering a promising paradigm for CEUS imaging and US-triggered chemotherapy. STATEMENT OF SIGNIFICANCE: Contrast-enhanced ultrasound (CEUS) imaging and US-triggered targeted chemotherapy efficacy of dual functional microbubbles (MBs) is often compromised by heterogeneous receptor expression and the endothelial cell barrier of solid tumors. This study introduces a modular bioorthogonal platform that decouples tumor targeting from genetic markers by converting metabolic flux into a robust chemical interface for MBs anchoring. We demonstrate that this stable chemical-mechanical coupling enables localized cavitation to physically breach the tumor stroma, providing a scalable and universal framework for CEUS imaging and US-triggered targeted chemotherapy.

Day-of-surgery cancellation of elective surgery causes patient harm, wastes theatre capacity, and reflects wider perioperative system pressure. In England, the principal public source for routine surveillance is the NHS England Quarterly Monitoring of Cancelled Operations (QMCO) collection, but direct comparison between NHS trusts and independent-sector providers remains methodologically difficult. This revised narrative review synthesised 10 publicly available NHS England datasets/documents and 13 supporting peer-reviewed or policy sources relevant to elective surgery cancellation and independent-sector provision. Publicly available national time-series data show that last-minute non-clinical cancellation rates have generally remained around 1% of elective admissions since the early 2000s, whereas the proportion of cancelled patients not treated within 28 days increased substantially after the COVID-19 pause in data collection. In the latest official commentary, 21,456 operations were cancelled at the last minute in the third quarter (Q3) 2025/26, and 4,821 patients (22.5%) breached the 28-day standard. Recent provider files identify only a small number of independent-sector organisations. Across the public extracts reviewed from 2021/22 to 2025/26 (Q1-Q3), identifiable independent-sector providers accounted for 296 cancellations versus 337,004 in NHS organisations, contributing under 0.2% of recorded cancellations in each year examined. However, the public files do not provide matched provider-level denominators or case-mix adjustment, and the reporting scope has changed over time. The main conclusion is therefore methodological: current public English data are suitable for surveillance of NHS-funded last-minute cancellations, but they do not permit a fair denominator-matched comparison of day-of-surgery cancellation rates between NHS trusts and private providers. Future comparative work will require linked activity denominators, transparent provider classification, and standardised sector-wide reporting.

The global rise in mental health problems has outpaced the availability of trained professionals, prompting interest in digital solutions such as mobile mental health applications (apps). These apps offer potential benefits including cost-effectiveness, accessibility, and personalized care. Here we provide expert consensus recommendations for evaluating mental health apps, developed by a taskforce of the European College of Neuropsychopharmacology (ECNP) Digital Network using a Delphi process. The consensus group agreed that minimum evaluation criteria should include measures of efficacy, usability, acceptability, user satisfaction, and monitoring of potential adverse effects. Dropout rates were identified as a critical indicator of real-world app use. Accordingly, the task force emphasized the importance of examining barriers to user engagement, as well as patterns of app usage and attrition, as essential components of evaluation. App assessments must also address data security and explicitly report any breaches or other iatrogenic effects. Where feasible, evaluations should track time spent on the app and frequency of use. In addition, app development should incorporate equity and psychosocial considerations that may restrict access to digital technologies, highlighting the importance of co-design with end users. By establishing minimum standards and promoting evidence-based evaluation, this consensus seeks to support the responsible integration of mental health apps into care systems, ensuring they are safe, effective, and equitable tools within the mental health landscape.