bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of porcelain aorta on outcomes in transfemoral aortic valve implantation (TAVI) with balloon-expandable valves
Authors: Lauten Philipp , Kreutz Julian , Costello-Boerrigter Lisa C , Schreiber Mathias , Boerrigter Guido , Albert Christian , El Garhy Mohammad , Göbel Björn , Schieffer Bernhard , Lapp Harald , Owais Tamer , Kuntze Thomas , Markus Birgit 
Published: January 2025

BackgroundCurrent guidelines recommend transcatheter aortic valve implantation (TAVI) for patients with aortic stenosis and porcelain aorta (PA). Neurological outcomes of patients with PA undergoing TAVI with modern valves require clarification as most trials examined balloon-expandable valves (BEV) and self-expandable valves in intermediate or high-risk patients, but not specifically in patients with PA. Our aim was to compare outcomes, including stroke and mortality, in well-matched patients with and without PA who received BEV during transfemoral TAVI procedures.MethodsConsecutive patients undergoing TAVI were entered into a registry. For this single-centre (Zentralklinik Bad Berka, Germany), retrospective analysis, we only selected patients who received BEV. PA diagnosis was made when non-contrast axial CT images fulfilled Valve Academic Research Consortium-2 criteria for PA. There was 2:1 nearest neighbour matching of patients without and with PA. The primary outcome measure was 30-day mortality or stroke within 72 hours. Secondary outcome measures were 30-day mortality, stroke within 72 hours, technical success and 30-day device success.ResultsAfter matching patients with (n=141) and without PA (n=282), the primary outcome of mortality at <30 days or stroke within 72 hours was higher in PA versus non-PA (7.8% vs 2.5%; OR 3.32 (95% CI 1.25 to 8.85); p=0.019). With regard to secondary outcomes, PA was not associated with mortality at 30 days (4.3% vs 2.1%; OR 2.04 (95% CI 0.65 to 6.48); p=0.23); however, stroke within 72 hours was significantly higher in PA versus non-PA (3.5% vs 0.4%; OR 10.33 (95% CI 1.17 to 91.12); p=0.017). Technical and device success were uninfluenced by PA.ConclusionsTransfemoral TAVI with BEV in patients with PA was associated with a higher risk of the primary combined endpoint of mortality at 30 days or stroke within 72 hours, which was primarily driven by stroke within 72 hours. These findings might influence cerebral embolic protection device use in patients with PA.
Efficacy and safety of anti-thrombotic therapy after surgical mitral valve repair: a scoping review
Authors: Babadagli Hazal Ece , Ye Jian , Chen Jenny , Turgeon Ricky , Wang Erica HZ 
Published: January 2025

BackgroundMitral valve repair (MVr) is the gold standard treatment for degenerative mitral regurgitation, yet there is ongoing controversy regarding optimal anti-thrombotic therapy post-MVr. This scoping review aimed to summarise current evidence on the safety and efficacy of anti-thrombotic therapy after MVr, identify knowledge gaps and propose a future study design.MethodsWe searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, the WHO International Clinical Trials Registry Platform and bibliographies of included trials, guidelines and other reviews from inception to 17 September 2024. Randomised controlled trials (RCT) and cohort and case-control studies assessing any anti-thrombotic therapy with any outcomes after MVr were included. Using a predefined collection form, two authors independently extracted data on study characteristics and results were summarised narratively into themes based on the PICO elements.ResultsOf 1296 screened references, we included 11 studies (10 cohort and one non-inferiority RCT). All studies compared vitamin K antagonist (VKA) to an anti-platelet, direct oral anti-coagulant or no anti-thrombotic therapy for median duration of 90 days. Thromboembolic and bleeding event incidences ranged from 0% to 14.3% and 0% to 9.1%, respectively. Seven studies reported no difference in thromboembolic events, and three reported reduced rates with VKA compared with control, while results for bleeding events varied widely. The RCT found edoxaban was non-inferior to warfarin for thromboembolic outcomes, but not for bleeding. Substantial methodological and clinical heterogeneity, high risk of bias and insufficient mitigation of confounders, such as concomitant atrial fibrillation, were prevalent across studies.ConclusionBased on this scoping review, existing literature on anti-thrombotic therapy after MVr is inconclusive due to design limitations. We proposed a study design for a pragmatic RCT that addresses prior study limitations and that could provide definitive evidence to guide anti-thrombotic management in MVr patients.
Simulation models verification and validation: Recent development and challenges: A review
Authors: Biazen Melkamu Ambelu , Woldeyohannes Abraham Debebe , Gebeyehu Sisay Geremew 
Published: January 2025

Nowadays, verification and validation activities have become the prominent parameters to check the acceptability of a simulation model by the users for the intended purpose. This review paper aims to identify and analyze the recent development and challenges of simulation model verification and validation. To achieve this objective, a systematic review of the literature was carried out which mainly consisted of the methodological development of verification and validation process paralleled with simulation model development. Initially, a cumulative total of 980 records was found sourced from Google Scholar via an advanced search method, Science Direct, Web of science and from Scopus. Through a rigorous screening process about 72 sources or publications were included for analysis. The verification and validation techniques that have been developed so far were classified into five categories methodologically. From intensive analysis, it is found that researchers extensively scrutinize the traditional methods and graphical/ statistical tools, escalating interest in data-driven and automation techniques, and limited focus on agent-based and hybrid models. Though agent-based and hybrid models are increasingly vital in the realm of complex system simulations, their verification and validation processes remain relatively under-explored. Though reasonable efforts have been exerted on the verification and validation methods development, still academicians and researchers agreed on the lack of verification and validation methodology for the recently developed simulation model paradigms such as agent-based and hybrid models, autonomous robotics models, high fidelity and data-driven models, and real-time prediction models such as digital twins. As a challenge of verification and validation processes, lack of universal methodologies, lack of reliable real-world data for validation, inaccuracy of real-world data for the intended purpose, different world views by different individuals, and the rapid growth and complexity of simulation modeling are identified as the hindering factors of verification and validation process.
Complex Limb Injuries: Limb Salvage Versus Amputation—A Mini Review and Meta‐Analysis
Authors: Serlis Athanasios , Sgardelis Panagiotis , Vampertzis Themistoklis , Rizavas Konstantinos , Poulios Panagiotis , Konstantopoulos Georgios 
Published: January 2025

Introduction: The management of complex limb injuries can be very challenging, and it demands a multidisciplinary approach to treatment. Amputation and limb reconstruction are the two options that clinicians must choose. This study aims to comprehensively synthesize existing tools and resources from the literature that can assist clinicians in the decision‐making process.Evaluation: The initial resuscitation and the prehospital care are the first important steps in the management of these injuries, while the immediate transfer to trauma centers is recommended for complex cases. After the stabilization of the patient, a thorough clinical examination of the limb is necessary with emphasis on the degree of soft tissue damage. Blunt trauma in the lower limb is associated with a higher risk of early amputation. Polytrauma patients with complex limb injuries require a holistic approach, with Damage Control Orthopedics (DCO) principles. Traumatic bleeding significantly increases mortality rates, necessitating prompt control using pressure bandages or tourniquets. Computed tomography angiography (CTA) is necessary in order to assess the viability of the limb.Management: Scoring systems can be used as a tool in the management of complex lower and upper limb injuries. Mangled Extremity Severity Score (MESS) calculates ischemia, shock, bone and soft tissue damage, and patient characteristics. The Narakawa Index (NISSSA score) constitutes an alteration of MESS with the implementation of a nerve injury element. The Musculoskeletal Score for Severity of Injury (MESI score) estimates the risk of limb amputation by evaluating injury, neurovascular damage, type of fracture, patient characteristics, and the period from the occurrence of trauma to the definitive treatment. Further interventions and patient preferences should be incorporated into the decision‐making process.Outcome: The outcomes of limb salvage versus amputation for complex limb injuries encompass various factors, including patient’s preinjury health status, psychological well‐being, functional outcomes, and economic impact. While some studies suggest better psychological outcomes with limb reconstruction and others find similar functional outcomes between the two approaches, economic considerations play a significant role in decision‐making.Conclusion: Managing complex limb injuries effectively necessitates a comprehensive approach involving thorough assessment, multidisciplinary collaboration, and patient‐centered care. Given the diverse factors influencing management and long‐term outcomes, it is crucial to integrate medical expertise with patient preferences and expectations.
Emotional Abuse Against Women in the Context of Intimate Relationships: A Concept Analysis
Authors: Abusbaitan Hanan A. , Eyadat Anwar M. , Holt Jeana M. , Telfah Reem K. , Zahra Tala F. Abu , Zahra Tuleen F. Abu , Mobarki Amani A. , Mkandawire-Valhmu Lucy , Kako Peninnah M. , Gondwe Kaboni W. , Lopez Alexa A. 
Published: January 2025

Background: Emotional abuse of women is common and has significant health and social consequences. Emotional abuse often precedes physical and sexual abuse. Research centered on emotional abuse is limited when compared with other forms of abuse, such as sexual and physical abuse. A lack of understanding of emotional abuse in women can lead to negative health complications and failure to provide the most effective care. A close examination of the attributes of emotional abuse is needed to inform interventions that improve women’s health outcomes.Purpose: The purpose of this concept analysis is to explore the critical components of emotional abuse against women in the context of intimate relationships.Method: The Walker and Avant (2011) process was used to analyze the concept of emotional abuse. This analysis utilized quantitative and qualitative research studies. Studies in English from 2013 to 2023 were included. Evidence was reviewed to clarify the attributes, antecedents, consequences, and model cases of emotional abuse in women.Results: One hundred and two studies met the inclusion criteria. Four attributes of emotional abuse were identified, including humiliation, indifference, control, threat, and intimidation. Emotional abuse as a phenomenon is associated with women’s and partners’ influences, unhealthy relationships, the normalization of emotional abuse in society, and the lack of social support. Emotional abuse in women leads to poor psychological, perinatal, and intimate relationship problems.Conclusion: Nurses should understand the attributes, causes, and consequences of emotional abuse in women to help them recognize and address this issue in the clinical setting. Further studies are needed to increase nursing’s understanding of the experience of emotional abuse in women.
Exome sequencing reveals a sparse genomic landscape in Kaposi sarcoma
Authors: Phipps Warren , Bhinder Bhavneet , Towlerton Andrea , Mooka Peter , Kafeero James , Fitzgibbon Matt , Elemento Olivier , Cesarman Ethel 
Published: January 2025

Abstract
Kaposi Sarcoma (KS) is a frequently aggressive malignancy caused by Kaposi sarcoma herpesvirus (KSHV/HHV-8). People with immunodeficiencies, including HIV, are at increased risk for developing KS, but our understanding of the contributions of the cellular genome to KS pathogenesis remains limited. To determine if there are cellular genetic alterations in KS that might provide biological or therapeutic insights, we performed whole exome sequencing on 78 KS tumors and matched normal control skin from 59 adults with KS (46 with HIV-associated KS and 13 with HIV-negative KS) receiving treatment at the Uganda Cancer Institute in Kampala, Uganda. We found a very low mutational burden in all but one specimen (median=11 mutations), which is the lowest number of mutations among all 33 tumor types in The Cancer Genome Atlas (TCGA). No recurrent mutations were seen and the most commonly affected oncogenic pathway was RTK/RAS. Mutational signatures included defective DNA mismatch repair and smoking. There was no evidence suggesting that multiple tumors from the same patient originated from the same original clone. The number of genome copy alterations per genome were higher in tumors from those without HIV infection and in tumors from participants with advanced stage disease, suggesting that lesions that take longer to develop may accumulate more alterations, although the number of alterations remain low compared to other cancers. Implications: Our findings indicate that the pathogenesis of KS differs from other malignancies, and that the primary driver of carcinogenesis is KSHV viral infection and expression of viral oncogenes, rather than clonal oncogenic transformation.
Dynamic Tracking of Tumor Microenvironment Modulation Using Kaede Photoconvertible Transgenic Mice Unveils New Biological Properties of Viral Immunotherapy
Authors: Diers Anne R. , Guo Qiuchen , Li Zhi , Richardson Erin , Idris Suaad , Willis Claire , Tak Paul P. , Withers David R. , Barone Francesca 
Published: January 2025

Abstract
CAN-2409 is a replication-defective adenovirus that delivers the herpes simplex virus–thymidine kinase gene to infected cells. Intratumoral administration of CAN-2409, followed by prodrug, results in the formation of a toxic metabolite able to induce immunogenic cell death, exposure of tumor-associated antigens, and activation of local and systemic immune responses. We used a dynamic labeling model with MC38 tumor cells implanted in photoconvertible Kaede mice. Violet light was used to label the tumor microenvironment (TME), distinguishing retained versus newly entering cells and allowing real-time monitoring of immune compartment changes within tumors. Administration of CAN-2409 + prodrug led to control of tumor growth and significantly increased effector CD8+ T-cell responses. Photolabeling of the TME revealed that rather than enhancing recruitment of T cells to the tumor, CAN-2409 altered the TME whereby newly entering and retained CD8+ T cells were significantly more proliferative. CAN-2409 supported reinvigoration of tumor-associated antigen–specific CD8+ T cells and expansion of regulatory T cells of an altered phenotype. Moreover, the combination of CAN-2409 + prodrug and anti–CTLA-4 antibody treatment further improved control of tumor growth, in part by the enhanced CD8+ T-cell–mediated effector function and diminished regulatory T cell–mediated immunosuppression. Collectively, these data defined at least two temporally distinct pathways underpinning the mechanism of action of CAN-2409 that overcome cell exhaustion and decrease immune suppression. The results also support the rationale for future clinical trials of CAN-2409 treatment combined with anti–CTLA-4 antibody therapy.

Significance:
This study utilized a novel photoconvertible mouse tumor model to track immune cell trafficking upon treatment with an investigational viral immunotherapy (CAN-2409), revealing enhanced T-cell responses after viral immunotherapy associated with local proliferation of T cells within tumors that could further enhance antitumor efficacy in combination with immune checkpoint inhibitors. These findings define temporally and spatially distinct interactions of immune cells that could be harnessed by novel therapeutics.
Circulating ANGPTL3/8 Concentrations Are Associated With an Atherogenic Lipoprotein Profile and Increased CHD Risk in Swedish Population-Based Studies
Authors: Leander Karin , Chen Yan Q. , Vikström Max , Silveira Angela , Fisher Rachel M. , Konrad Robert J. , van ‘t Hooft Ferdinand M. 
Published: January 2025

BACKGROUND:
Binding of ANGPTL (angiopoietin-like protein)-3 to ANGPTL8 generates a protein complex (ANGPTL3/8) that strongly inhibits LPL (lipoprotein lipase) activity, as compared with ANGPTL3 alone, suggesting that ANGPTL3/8 concentrations are critical for the regulation of circulation lipoprotein concentrations and subsequent increased coronary heart disease (CHD) risk. To test this hypothesis in humans, we evaluated the associations of circulating free ANGPTL3 and ANGPTL3/8 complex concentrations with lipoprotein concentrations and CHD risk in 2 prospective cohort studies.

METHODS:
Fasting blood samples were obtained in conjunction with the baseline evaluation of 9479 subjects from 2 population-based Swedish cohorts of middle-aged men and women. Standard biochemical blood analyses, including all lipid/lipoprotein measurements, were performed in these samples at baseline. Additional serum samples were stored at −80 °C and used at a later stage for ANGPTL3 and ANGPTL3/8 concentration measurements. Information about incident CHD was obtained for both cohorts by matching to the Swedish National Patient Register and the Cause of Death Register.

RESULTS:
ANGPTL3 concentrations showed modest, positive associations with all lipoprotein concentrations but were not associated with CHD risk. In contrast, ANGPTL3/8 concentrations were associated in both cohorts with an atherogenic lipoprotein profile (characterized by increased triglyceride and LDL [low-density lipoprotein] concentrations and reduced HDL [high-density lipoprotein] concentrations). In the combined cohort, ANGPTL3/8 was associated with increased CHD risk. Hazard ratio per 1 SD increase was 1.10 (95% CI, 1.03–1.17) after adjustment for age, sex, cohort, smoking, and hypertension.

CONCLUSIONS:
Elevated concentrations of ANGPTL3/8, but not ANGPTL3, are associated with an atherogenic lipoprotein profile and increased CHD risk in humans.
Abolition of Aorticorenal Ganglia Pacing Responses Improves Denervation Efficacy
Authors: Balaji Poornima , Liu Xingzhou , Tran Vu Toan , Barry Michael A. , Vien Albert , Yang Edward , Nguyen Duc Minh , Patel Urja , Lu Juntang , Alvarez Shirley , Bandodkar Sushil , Varikatt Winny , McEwan Alistair , Thomas Stuart P. , Qian Pierre C. 
Published: January 2025

BACKGROUND:
Transcatheter renal denervation (RDN) remains inconsistent despite developments in ablation technologies, due to the lack of an intraprocedural physiological end point. The aim of this study was to identify if aorticorenal ganglion (ARG) guided RDN using microwave (MW) catheter leads to more consistent denervation outcomes compared with empirical MW ablation.

METHODS:
Pigs underwent sham procedure (n=8) or bilateral RDN using an in-house built open-irrigated MW catheter. Before denervation, ipsilateral ARG pacing was performed leading to renal artery vasoconstriction. MW ablation group (MW-group; n=7) received 1 ablation (100–120 W for 360 seconds) in the mid-main renal artery based on artery caliber. ARG-guided-MW ablation group (ARG-MW-group; n=7) was permitted an additional ablation more distally or at higher power until a vasoconstrictive response was abolished. Animals were euthanized at 4 to 5 weeks post-procedure.

RESULTS:

ARG pacing caused an ipsilateral reduction in renal artery caliber from 4.67 to 4 mm;
P
=0.0006 in MW-group and 4.8 to 3.9 mm;
P
=0.001 in ARG-MW-group. Repeat ARG pacing at euthanasia led to a reduction in renal artery caliber in MW-group from 5.1 to 4.8 mm;
P
=0.006, but not in ARG-MW-group from 4.88 to 4.55 mm;
P
=0.08. There were no differences in ablation injury volumes between the groups. Compared with undenervated sham controls, ARG-MW-RDN versus MW-RDN caused median reductions in viable nerve area (antityrosine hydroxylase staining) at 4 to 5 weeks by 92.6% (interquartile range, 0.94–19.59%;
P
<0.0001) versus 55.02% (interquartile range, 15.87–75.11%;
P
=0.006) and median renal cortical norepinephrine content by 68.06% (interquartile range, 27.16–38.39%;
P
<0.0001) versus 25.25% (interquartile range, 56.97–157.7%;
P
=NS).

CONCLUSIONS:
ARG pacing serves as a physiological procedural end point to guide MW denervation to improve denervation outcomes.
Abstract TMP50: How Often Do Patients Sleep Through the Onset of Ischemic Stroke?
Authors: ANDREASYAN LYNETTE , Saver Jeffrey 
Published: January 2025

Introduction:
The advent of wireless monitoring technologies to detect stroke onset during sleep has the potential to accelerate reperfusion treatment in the 20-25% of patients with wake-up stroke. Monitoring technologies will hasten stroke detection in patients who sleep through stroke onset but not in patients who are awakened by stroke onset. The relative frequencies patients who stay asleep after onset compared with patients who wake up with onset has not been well

delineated.

Methods:
We performed a systematic search and meta-analysis of studies comparing diffusion-weighted imaging–fluid-attenuated inversion recovery (DWI-FLAIR) mismatch frequencies in wake-up stroke (WUS) compared with clear onset time stroke (COS). Differences in WUS vs COS decay curves in frequency of FLAIR-DWI mismatch with longer time from symptom detection to imaging were used to estimate the time of stroke onset during sleep.

Results:
Two studies of WUS and COS patients met selection criteria, collectively enrolling 443 patients (201 WUS, 242 COS). The frequencies of FLAIR-DWI mismatch at different intervals from symptom-detection-to-imaging are shown in Figure 1. For COS patients, frequency of mismatch presence declined gradually: <2h 60%; 2-3h 53%; 3-4h 41%; 4-5h 37%; 5-6h 11%. In contrast, for WUS patients, <2h patients had similar mismatch rates to <2h COS patients but

mismatch frequency then declined precipitously in all later time windows: <2h 50%; 2-3h13%; 3-4h 13%; 4-5h 6%; 5-6h 12%. Among the WUS patients: 16.9% had detection-to-imaging time in the <2h time period in which mismatch was nearly equally present as in COS patients; 70.1% had detection-to-imaging times with mismatch rates whose COS equivalents indicated stroke onset 1-8h prior to awakening; and 13.0% had detection-to-imaging times of indeterminate
stroke onset time.

Conclusions:
About 5 of every 6 patients with stroke first detected on awakening had remained asleep for 1-8 hours after stroke onset, while 1 of every 6 awoke at the time of, or soon after, onset. These findings indicate that wireless monitoring technologies to detect stroke start during sleep would accelerate stroke detection in many WUS patients.