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The durability of surgical aortic valve replacement prostheses can be limited due to structural valve deterioration over the years. Because of increased patient age and surgical risk, many of these patients are treated with valve-in-valve transcatheter aortic valve replacement (TAVR). Full expansion of the valve is often difficult to achieve in these patients, which might negatively affect the hemodynamic outcome. The aim was to investigate whether incomplete expansion of valve-in-valve TAVR correlates with an unfavorable hemodynamic outcome. A retrospective monocentric study with 152 patients who received a valve-in-valve TAVR between 2014 and 2024 at the University Heart Centre Freiburg-Bad Krozingen, Germany, was performed. The expansion and implantation depth of the TAVR prostheses were measured in the angiographic recordings and correlated with the postinterventional hemodynamic outcome. 69.7% of the patients received self-expanding and 28.9% balloon-expandable TAVR prostheses during the valve-in-valve procedure. Under-expansion in the waist area of self-expanding valve prosthesis was associated with increased postinterventional mean pressure gradients. Post-dilation significantly improved the waist expansion in self-expanding valve prostheses (median increase 7.8%, p&#x2009;<&#x2009;0.0001). Further, a correlation between implantation depth and waist expansion was observed in self-expanding valves (Spearman r&#x2009;-&#x2009;0.4481, p&#x2009;<&#x2009;0.0001), but not in balloon-expandable valves. Under-expansion of the waist area of self-expanding valve-in-valve TAVR was associated with an unfavorable hemodynamic outcome. A periinterventional measurement of the angiographic images after valve release might be useful to assess a relevant under-expansion and to assist in the indication for post-dilation. The study has been registered in the German Clinical Trials Register (DRKS-ID: DRKS00029242), date: 27/03/2023.

Polydopamine (PDA), a mussel-inspired functional polymer, has become a key material for sensors and biomedical systems due to its exceptional adhesion, redox activity, and versatile surface chemistry. Unlike existing reviews that often treat PDA's fundamental chemistry and specific medical uses separately; this article addresses a critical gap by directly bridging PDA's structural properties to its practical performance in advanced technologies. Advances in controlled PDA polymerization have enabled the design of tailored nanostructures such as nanoparticles, hollow nanocapsules, thin films, and hybrid coatings that enhance performance across multiple biomedical platforms. In sensing and biosensing, PDA facilitates efficient biomolecule immobilization, improves electron transfer, and enables selective detection of biomarkers, making it highly effective for electrochemical, optical, and wearable sensor devices. In biomedicine, PDA's biocompatibility, photothermal properties, and ease of functionalization support a wide range of applications, including targeted drug delivery, multimodal cancer therapy, photothermal-chemotherapy combinations, tissue engineering scaffolds, wound healing materials, and controlled-release systems. By integrating recent progress in PDA structure, synthesis, and functionalization strategies, this review provides a comprehensive and application-oriented perspective on the expanding role of PDA in sensing technology and advanced biomedical engineering.

Managing patients with respiratory failure increasingly involves non-invasive respiratory support (NIRS) strategies to support respiration, often preventing the need for invasive mechanical ventilation. However, despite the rapidly expanding use of NIRS, there remains a significant challenge to its optimal use across all medical circumstances. It lacks a unified ontological structure, complicating guidance on NIRS modalities across healthcare systems. In this study, we introduced NIRS ontology to support knowledge representation in acute care settings by providing a unified framework that enhances data clarity and interoperability, laying the groundwork for future clinical decision-making research. We developed NIRS ontology using the Web Ontology Language (OWL) and Prot&#xe9;g&#xe9; to organize clinical concepts and relationships. To enable rule-based clinical reasoning beyond hierarchical structures, we added Semantic Web Rule Language (SWRL) rules. We evaluated logical reasoning using a sample of 6 patient scenarios and used SPARQL queries to retrieve and test targeted inferences. The ontology has 145 classes, 11 object properties, and 18 data properties across 949 axioms that establish concept relationships. To standardize clinical concepts, we added 392 annotations, including descriptive definitions based on controlled vocabularies. SPARQL queries successfully validated all test cases (rules) by retrieving appropriate patients' outcomes: for instance, a patient treated with HFNC (high-flow nasal cannula) for 2 hours due to acute respiratory failure may avoid endotracheal intubation. This NIRS ontology formally represents domain-specific concepts, including ventilation modalities, patient characteristics, therapy parameters, and outcomes. SPARQL query evaluations across clinical scenarios confirmed the ontology's ability to support rule&#x2011;based reasoning and therapy recommendations, providing a foundation for consistent documentation practices, integration into clinical data models, and advanced analysis of NIRS outcomes. In conclusion, this proof-of-concept NIRS ontology demonstrates how clinical concepts can be formally represented and queried, offering a foundation for future validation, EHR integration, and evidence-based refinement of NIRS practices.

Percutaneous cervical cordotomy (PCC) is a minimally invasive radiofrequency procedure for intractable unilateral cancer pain. Commonly performed under conscious sedation, awake PCC enables real-time patient feedback, potentially improving targeting precision and expanding eligibility for patients in whom sedation poses risks. This article presents the structured protocol for awake PCC implemented at our center, including pre-procedural training, positioning, fluoroscopic guidance, impedance monitoring, sensory and motoric testing, lesioning strategy, and aftercare. The key principle is to create the smallest effective lesion, applied incrementally until spinothalamic tract disruption is confirmed. In our experience, awake PCC enables precise targeting and has yielded up to 90% success in pain relief. The approach requires substantial preparation, including training for both patient and team to ensure cooperation, clear communication, and tolerance of brief intraoperative discomfort. Although these demands can be challenging, we have found awake PCC to be a safe and effective last-resort option for patients facing devastating pain. This technical note provides a practical and stepwise approach to awake PCC. It may assist clinicians in adopting or refining the technique.

Plant viruses are recognized as rapid and effective vectors to deliver CRISPR-Cas reaction components into plants, a strategy termed virus-induced gene editing (VIGE). However, VIGE is limited by the host range of the viral vectors. Development of new viral vectors to target a broad range of plant species will potentially enable the delivery of the editing components to new cultivars. Potyviruses (genus Potyvirus) comprise the largest group of plant RNA viruses. The main limitation of potyviral vectors to express a non-coding RNA consists of potential insertion of stop codons that interrupt the large open reading frame that encompasses most potyviral genome. This is the case with the Streptococcus pyogenes Cas9 sgRNA scaffold, which contains stop codons in all three possible frames. In this work, we first built on a visual reporter system targeting the two homeologs of Nicotiana benthamiana Magnesium chelatase subunit I (CHLI). Second, we developed a tobacco etch virus (Potyvirus nicotianainsculpentis)-derived vector for VIGE by engineering a modified Cas9 scaffold, free of stop codons, to maintain the potyviral polyprotein reading frame while ensuring effective editing. This vector self-replicates and moves systemically, delivering sgRNAs efficiently throughout the plant. This allowed us to obtain plants exhibiting a white phenotype with their four alleles edited through in&#xa0;vitro regeneration from infected leaves, and also to produce edited progeny. We further demonstrated the vector utility in tomato. Given the conserved biological properties within the genus Potyvirus, these findings may be broadly applicable to other potyviruses, expanding the reach of the VIGE technology.

Peptidoglycan Recognition Proteins (PGRPs) are conserved pattern-recognition receptors that detect microbe-associated molecular patterns (MAMPs) and activate host immune responses. Compared to other dipterans, the tsetse fly (Glossina morsitans morsitans) genome encodes only five PGRPs- PGRP-LA, -LB, -LC, -SA, and -SB - far fewer than most dipterans, likely reflecting its sterile blood diet and streamlined microbiota. Here, we identify PGRP-LA as a critical regulator of peritrophic matrix (PM) integrity in the cardia (proventriculus), the tissue responsible for PM production. The PM is a chitinous sleeve-like barrier that separates the midgut epithelium from the ingested bloodmeal, supporting digestive homeostasis and infection resistance. We show that pgrp-la is prominently expressed in the cardia, transiently induced after a bloodmeal in newly eclosed flies, and reinduced following subsequent feedings, likely in response to blood- constituents or mechanical stretch. This induction is sustained during microbial exposure and prolonged in trypanosome-infected flies. RNAi-mediated reduction of pgrp-la significantly increased the prevalence of midgut trypanosome infections, indicating a protective role during early infection. PGRP-LA did not mediate infection resistance via canonical IMD pathway signaling, as its silencing did not affect antimicrobial peptide expression. Instead, PGRP-LA modulated the expression of PM-associated genes and gut barrier integrity. Silencing pgrp-la reduced PM structure, increased midgut weights and enhanced fly survival following oral challenge with entomopathogen Serratia marcescens, likely due to earlier epithelial immune responses through a compromised PM. Similar phenotypes were observed when flies were fed anti-PGRP-LA antibodies, supporting a structural role for PGRP-LA. In addition, soluble variant surface glycoproteins (sVSGs) from trypanosomes and knockdown of microRNA-275 (miR-275), also decreased pgrp-la expression, suggesting that PGRP-LA is part of a broader regulatory network, including the miR-275/Wingless signaling. Collectively, our results identify PGRP-LA as novel regulator of PM biogenesis and vector competence in tsetse, expanding the functional repertoire of PGRPs in insect gut barrier maintenance beyond canonical immune signaling pathways.

Crimean-Congo hemorrhagic fever (CCHF) is an emerging tick-borne disease with a growing global distribution. In Armenia, 31 Ixodidae tick species have been identified, including Hyalomma species. While CCHF virus (CCHFV) was previously isolated from ticks in the 1970s, no further studies were conducted until 2016, when antibody to CCHFV was identified.This study aimed to update data on the Ixodidae tick species, detect CCHFV in collected specimens, and perform molecular characterization of viral lineages circulating in Armenia during 2022-2024.Epizootiological investigations were performed across all 10 regions of Armenia. Fieldwork involved the collection of Ixodidae ticks, followed by morphological identification and testing of specimens. A total of 550 animals (including cattle, sheep, and horses) and surrounding open habitats were surveyed, resulting in the collection of 3158 Ixodidae ticks representing 12 species. These samples were organized into 960 pools and tested via reverse transcriptase polymerase chain reaction for CCHFV. Viral RNA was detected in 96 pools, all originating from ticks collected from cattle and representing 8 species. Positive samples were confined to two regions: Syunik and Tavush. Phylogenetic analysis revealed the presence of two CCHFV lineages in Armenia: Europe 1 (Subgroup V) and Europe 3 (Subgroup VII).Armenia's climatic and geographic diversity, expanding land use, population mobility, and growing tourism highlight the need for continued surveillance. The present identification of CCHFV in ticks in two regions emphasizes the importance of ongoing epizootiological monitoring and molecular characterization to assess the broader epidemic risk across the country.

The field of extracellular vesicles (EVs) has advanced considerably in recent years with new findings stemming from technical improvements in their isolation and characterization, expanding their potential as tools in vaccines, drug delivery, and timely diagnosis using biomarkers. Consequently, a new area of interest has recently gained prominence: the study of changes in EV morphology and their potential involvement in diseases. Using cryo-TEM analysis, a technique that helps preserve the near-natural state of EVs, multiple morphological and structural variants have been demonstrated in isolates from bodily fluids, cell cultures, and cell lines of mammals, as well as some protozoa and plants. In addition to the classic sphere with a lipid bilayer and hyaline content, pleomorphic, tubular and sac-like EVs, with double, multilayered or lamellar membranes, and in some cases, with electrodense content, have been described. Furthermore, several studies have found alterations in the morphological pattern and/or proportions of these morphological variants in diseases associated with cellular or metabolic dysfunction such as Parkinson's and diabetes, as well as in infectious diseases such as Zika virus and prions. Here, we review the key findings that have propelled the field, provide a catalog of the EVs variants identified to date, discuss mechanisms underlying their formation and their potential biological implication in the course of various pathologies, and identify key challenges that need to be addressed. The information analyzed demonstrate that EVs are highly variable structures, not only in their content but also in their morphology, and that this variation could be related to cellular, metabolic, and infectious pathologies. This underscore the need to understand the origin, regulation, and function of each morphological type of EVs, which could lead to their possible use as diagnostic or therapeutic tools in the future. Findings from the last decade using cryo-TEM in bodily fluids demonstrate the existence of morphological and structural variants of extracellular vesicles (EVs).Emerging evidence from microorganisms and plants suggests that this phenomenon may represent a widespread biological process across nature.Changes in EV morphological variants and their proportions have been reported in several diseases involving metabolic and cellular dysfunction, as well as in some infectious diseases.

Euglena gracilis strain Z is currently used for industrial purposes such as the production of the polysaccharide paramylon, lipids, and carotenoids. This strain shows promise for sustainable bioproduction, but its growth is inhibited at temperatures below 20&#xb0;C, limiting its geographic range for outdoor cultivation. Here, we discovered a new low temperature-adapted E. gracilis ecotype, strains min34 and min41, in freshwater from a northern prefecture of Japan. These strains were isolated during the participatory science project "Everyone's Euglena Project." Strain min41 thrives at 15&#xb0;C, achieving cell densities and dry weights of 5.2- and 7.5-times higher than those of strain Z, respectively. Strain min34 also showed high growth ability at 15&#xb0;C but was inferior to strain min41. Whereas strain Z exhibits reduced bioproduction capacity at 15&#xb0;C (as evidenced by decreased paramylon, lipid, and carotenoid production), strain min41 maintains high bioproductivity at low temperature. Our findings underscore the rich genetic potential within E. gracilis for adaptation to diverse conditions and offer a valuable bioresource for exploring temperature-adapted systems, broadening the prospects for biomass production.IMPORTANCEOutdoor cultivation of microorganisms for bioproduction is often limited by temperature. Industrially useful E. gracilis strain cannot grow well in colder climates, restricting their use in sustainable industries such as food and biofuel production. In this study, we identified a new low temperature-adapted strain of E. gracilis that can thrive and remain productive at 15&#xb0;C. This strain could enable year-round biomass production in regions with colder weather, expanding the potential of environmentally friendly biomanufacturing. Our discovery also highlights the untapped natural diversity of this microorganism, which may hold the key to developing more resilient and efficient bioproduction systems.

Culturally adapted parent training prevention interventions are critical for supporting the mental health and resilience of Latine immigrant families. Following the onset of the COVID-19 pandemic, parent training programs transitioned to online delivery, increasing flexibility and expanding access. This qualitative study explored the experiences of first-generation Latine immigrant caregivers (N = 22) in central Texas-86.4% of whom were of Mexican origin-who participated in a culturally adapted, synchronous online parent training program during the pandemic. Most participants were mothers (21 of 22). Through thematic analysis of focus group data, four key themes were generated: (a) immigration-related experiences and parenting challenges, (b) intervention components that addressed these challenges, (c) barriers and facilitators to participation, and (d) ongoing parenting needs. Caregivers reported increased parenting confidence and skill acquisition, alongside a sense of validation and support through the online community. While the virtual format enhanced accessibility, some participants encountered technological barriers. Key facilitators included the cultural competence of interventionists and the creation of a safe space for sharing immigration experiences. Participants highlighted the needs for further adaptation, including more father engagement, adolescent-focused content, and support in addressing intergenerational parenting patterns. Findings underscore the importance of creating therapeutic spaces that acknowledge immigration-related trauma and stress while building parental resilience and family well-being. These findings provide valuable insights for improving online synchronous delivery formats to enhance accessibility while maintaining program effectiveness and cultural responsiveness, promoting mental health equity for immigrant communities. Clinical and empirical implications are discussed. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Quantifying collagen in histological slides is essential for diagnosing and monitoring fibrosis. However, the combination of PicroSirius Red staining with polarized light microscopy, one of the standard techniques, requires expensive equipment and time-consuming procedures. This study investigated whether supervised machine learning algorithms applied to bright-field images could provide an automated and accurate method for collagen segmentation, reducing the dependence on polarized imaging. A total of 140 histological images of renal, cardiac, and tendinous tissues from mice and rats stained with PicroSirius Red were analyzed. The images were fragmented into smaller patches, and the green channel was selected for non-polarized analysis. The reference standard was generated from polarized images binarized using ImageJ. Two supervised models were evaluated: (1) a Multilayer Perceptron (MLP) trained using five features (RGB intensities, median filter, and Wavelet), and (2) a U-Net architecture adapted to the image dimensions. Both models performed well, with the best results observed in rat tendon samples (Dice and precision&#x2009;>&#x2009;80%). Performance was lower in mouse kidney images, possibly due to weaker staining and thinner collagen fibers. Overall, the MLP slightly outperformed the U-Net, which still showed comparable results. The proposed methodology proved effective for collagen segmentation highlighting the potential of supervised learning to reduce costs and processing time in histological analysis. Future improvements include expanding the dataset and refining the reference standard to enhance robustness in biological tissue evaluation.

Clinical decision support using heterogeneous electronic health records (EHRs) is a well-established yet rapidly expanding research area. Large language model (LLM)-driven approaches have shown dominant performance in processing unstructured data such as clinical notes for disease phenotype classification. However, the absence of a unified reasoning framework capable of integrating structured laboratory results with unstructured clinical notes under zero-shot conditions limits progress in multimodal clinical decision support. To address this gap, we propose MediPhen, a novel reasoning framework that transfers LLMs for multi-morbidity disease phenotyping using multimodal clinical data. MediPhen introduces a framework for adapting LLMs to zero-shot disease phenotyping by incorporating extracted clinical entities, their relations, and lab narratives from EHRs, integrating a clinical knowledgebase to guide phenotype classification and enhance LLM transfer learning performance, and an explanation module that leverages chain-of-thought prompting to improve clinical reasoning. Comprehensive experiments conducted on MIMIC-III and MIMIC-IV benchmarks across multiple LLMs demonstrate the effectiveness of MediPhen. Notably, MedGemma-27B achieved state-of-the-art performance, improving micro averaged F1 scores by 19.92% on MIMIC-III and 16.68% on MIMIC-IV compared to fine-tuned baselines. These results highlight MediPhen as a zero-shot screening tool for multi morbidity phenotype classification, scalable within research infrastructures, advancing integration of structured and unstructured EHR data in clinical AI.

By 2050, adults aged 65 and older will comprise roughly one-quarter of the United States population, heightening the importance of understanding factors that shape older adults' residential choices. While most prefer to remain in familiar homes and communities, many relocate to senior-living communities such as retirement homes, board-and-care residences, or nursing homes. Among the factors that may shape these transitions, declining driving ability may be especially relevant in the US, where older adults remain heavily dependent on private vehicles to meet everyday needs, access healthcare, and maintain social connections. As driving becomes more difficult or impossible, older adults may face growing challenges to independent living. Yet the role of driving decline in residential transition has received limited empirical attention. This study uses nine waves of the National Health and Aging Trends Study (NHATS) from 2011 to 2019. A discrete-time event-history model was used to examine whether older adults' driving status and experiences of driving-related challenges predict residential transitions to senior-living communities. Non-driving status strongly predicts residential relocation. However, individuals who voluntarily self-regulate driving face relocation risks similar to those who have already ceased driving entirely. Among non-drivers, timing matters: older adults who recently ceased driving are substantially more likely to relocate than peers who stopped over a decade earlier, whose risk approximates that of current drivers. These findings suggest that policy interventions aimed at expanding alternative transportation options may help older adults maintain independence and reduce the risk of entering senior-living communities.

Humans are uniquely adept at cultivating positive, xenophilic relationships beyond their immediate group, forming bonds through various mechanisms such as trade, exogamy, and shared defense. Despite the significance of intergroup cooperation, synthetic approaches to understanding the evolutionary, ecological, and institutional drivers of xenophilia remain underdeveloped compared to the wealth of research on intergroup conflict. Here, I synthesize ethnographic, archaeological, psychological and comparative evidence to argue that xenophilia is supported by recurrent human cognitive and social capacities whose expression and stability depend on ecological, economic and institutional contexts. The aims of this paper are threefold: first, to clarify the selective pressures and incentives that favour peaceful intergroup relations, with particular attention to factors contributing to amicable intergroup ties and expanding the circle of tolerance and cooperation, including economic interdependence through trade and reciprocity, information exchange, exogamy, and the necessity of collective defense against external threats; second, to examine how these different drivers of xenophilia interact and under what conditions they generate, stabilize or fail to sustain intergroup tolerance; and third, to place human xenophilia in comparative perspective by highlighting both parallels and distinctions with non-human primates in their strategies for fostering intergroup peace. By distinguishing between mechanisms that generate cooperation and those that stabilize it in the face of freeriding and defection, this synthesis highlights how humans uniquely scale and institutionalize intergroup peace. This perspective is particularly timely, as uncovering the evolutionary roots of tolerance and cooperation across group boundaries remains crucial for addressing pressing global challenges such as climate change, poverty, famine, conflict, and disease.

Climate-sensitive hazards-heat, wildfire smoke, floods, and hurricanes-increase morbidity and mortality and disrupt routine care, yet US policy centers on disaster declarations rather than day-to-day hazards. We outline a practical framework to integrate climate adaptation into health insurance coverage, using public indicators such as heat alerts and air quality indices to trigger regional activations that last for the duration of the hazard window. Actions follow two pathways: reduce exposure during short high-risk periods by providing supports such as cooling access and indoor air filtration, and when routine channels fail, preserve care by expanding access during hazard windows using exceptions such as early refills and temporary network flexibilities. Near-term implementation channels include Medicaid Section 1115 demonstrations and "in lieu of services" provisions (which allow a state to substitute cost-effective services outside of its federally approved state Medicaid plan); Medicare Advantage supplemental benefits and Special Needs Plans; existing emergency authorities; and commercial plan flexibilities, following comparable domestic and international precedents. As climate risks grow, embedding adaptation in health insurance systems may be among the most practical and scalable strategies to protect population health.

To explore the role of ischemic cryptogenic vascular dissection (CVD) in a patient presenting with overlapping symptoms of amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia (SCA), and the impact of endovascular treatment on posterior circulation hypoperfusion, cerebellar atrophy, and clinical symptoms. A 22-year-old male patient with progressive neurological symptoms underwent MRI, CTA, and genetic testing, revealing cerebellar atrophy, a novel TGM6 gene variation associated with SCA type 35, and SETX gene deletions linked to ALS type 4. Ischemic CVD was diagnosed via dynamic contrast-enhanced CT (DCE-CT) and treated with endovascular stent repair followed by dual antiplatelet therapy. Following endovascular treatment, posterior circulation hypoperfusion and cerebellar atrophy were significantly improved. MRI follow-up showed increased cerebellar size and reduced interlobar spacing, with cerebellar dimensions expanding by up to 26.98% and interlobar spacing narrowing by up to 27.14%. Concurrently, the patient experienced marked improvement in clinical symptoms. At the 21-month follow-up, the patient's Modified Rankin Scale (MRS) score was rated as favorable. Ischemic CVD may underlie overlapping ALS and SCA symptoms, suggesting a genetic-vascular link. Endovascular treatment of CVD led to improvements in posterior circulation hypoperfusion, cerebellar atrophy, and clinical symptoms, supporting further investigation into this potential pathogenic nexus.

Hearing is a vital part of human experience. It serves as a medium for communication, shapes perception of the world, and facilitates the formation of meaningful relationships. Thus, when hearing loss occurs, it can have a profoundly life-altering and detrimental impact on an individual. Hearing loss can be attributed to a variety of causes, including genetics, aging, medications, and disease processes. Commonly used medications, such as antibiotics, diuretics, and antineoplastics, can damage the inner ear's delicate internal structures, leading to hearing loss-a condition known as ototoxicity. Early recognition and treatment are crucial in preventing irreversible damage from these medications, and nurses play a vital role in this process. In the home healthcare setting, nurses serve as advocates, fostering trusting relationships with patients to promote patient safety and ensure effective monitoring and education. Numerous studies have discussed ototoxicity and emphasized the need for consistent monitoring, guidelines, and protocols; however, there is a notable lack of research investigating nursing-based interventions and acknowledging the critical role of nurses in implementing these preventive measures in home healthcare. The objective of this manuscript is to discuss an individual's experience with permanent hearing loss due to ototoxicity, highlighting the vital role nurses play in preventing these devastating effects. It emphasizes expanding the nurse's role in home healthcare to improve the timely detection and monitoring of ototoxicity. Proposed strategies include nursing assessment checklists, structured patient education handouts, and symptom diaries. By outlining key nursing interventions and proposed evaluation strategies, this manuscript raises awareness of how medication-induced, irreversible hearing loss can be mitigated through proper patient education and nursing-based monitoring in the home healthcare setting.