bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in serum cholesterol loading capacity are linked to coronary atherosclerosis progression in rheumatoid arthritis
Authors: Karpouzas George Athanasios , Papotti Bianca , Ormseth Sarah R , Palumbo Marcella , Hernandez Elizabeth , Adorni Maria Pia , Zimetti Francesca , Ronda Nicoletta 
Published: December 2024

ObjectiveExcess cholesterol loading on arterial macrophages is linked to foam cell formation, atherosclerosis and cardiovascular risk in rheumatoid arthritis (RA). However, the effect of changes in cholesterol loading on coronary plaque trajectory and the impact of RA therapies on this relationship are unknown. We investigated the association between variations in cholesterol loading capacity (CLC) over time and atherosclerosis progression.MethodsIn a prospective observational cohort study, coronary CT angiography evaluated atherosclerosis (non-calcified, partially calcified or fully calcified plaques and coronary artery calcium (CAC) score) in 100 patients with RA without cardiovascular disease at baseline and 6.9±0.4 years later. The presence of ≥5 plaques and lesions rendering >50% stenosis was considered an extensive and obstructive disease, respectively. Serum CLC was measured on human THP-1 monocyte-derived macrophages with a fluorometric assay.ResultsMean CLC change (follow-up CLC−baseline CLC) was 1.54 (SD 3.69) μg cholesterol/mg protein. In models adjusting for atherosclerotic cardiovascular disease risk score, baseline plaque and other relevant covariates, CLC change (per SD unit increase) is associated with a higher likelihood of progression of non-calcified (OR 2.55, 95% CI 1.22 to 5.35), fully calcified plaque (OR 3.10, 95% CI 1.67 to 5.76), CAC (OR 1.80, 95% CI 1.18 to 2.74) and new extensive or obstructive disease (OR 2.43, 95% CI 1.11 to 5.34). Exposure to prednisone unfavourably influenced, while biologics and statins favourably affected the relationship between CLC change and atherosclerosis progression (all p-for-interactions ≤0.048).ConclusionCLC change is associated with atherosclerosis progression in a dose-dependent manner, including lipid-rich non-calcified plaques and extensive or obstructive disease that yield the greatest cardiovascular risk.
Thermodynamic of the f(Q) universe
Authors: Rao Haomin , Liu Chunhui , Geng Chao-Qiang 
Published: December 2024

Abstract
We investigate thermodynamics of apparent horizon in the f(Q) universe with trivial and nontrivial connections. We first explore the perspectives of the first law, generalized second law and P–V phase transition with trivial connection. We show that the lowest-order correction of entropy has the same form as that in loop quantum gravity, and the critical exponents of the phase transition caused by the lowest-order correction are consistent with those in mean field theory. We then examine the thermodynamic implication of nontrivial connections. We find that nontrivial connections in the f(Q) universe imply non-equilibrium states from the perspective of thermodynamics.
Ten‐Year Outcomes and Predictors of Mortality Following Catheter Ablation of Ventricular Tachycardia
Authors: Rottner Laura , Metzner Andreas , Hochadel Matthias , Senges Jochen , Willems Stephan , Ince Hüseyin , Eckardt Lars , Deneke Thomas , Lugenbiel Patrick , Brachmann Johannes , Chun Julian , Tilz Roland , Rillig Andreas 
Published: December 2024

Background
Catheter ablation is the primary treatment option for idiopathic ventricular tachycardia (VT). It plays a key role in acute therapy of electrical storm, treatment of VTs in patients with structural heart disease (SHD), and can reduce VT burden. Here we report on 10‐year clinical outcomes following VT ablation from patients enrolled in the prospective German Ablation Registry.

Methods and Results
Long‐term follow‐up was conducted on 334 patients undergoing VT ablation (118/334, 35%) with structurally normal hearts and 216 out of 334 (65%) with SHD, including 161 out of 216 (75%) with ischemic heart disease at 38 centers. Follow‐up was completed in 94.8% of patients. Median observation time was 10.8 (4.3–12.3) years, with a 10‐year all‐cause mortality rate of 39.4%. VT ablation in patients with SHD was associated with worse outcome when compared with patients with structurally normal hearts (estimated 10‐year mortality for SHD 54.8% versus structurally normal hearts 12.1%). Estimated 10‐year mortality following VT ablation was highest in patients with ischemic heart disease (62.4%). Significant predictors of mortality following VT ablation included age (hazard ratio [HR], 2.35 [1.90–2.92] per decade), left ventricular ejection fraction ≤30% (HR, 2.11 [1.44–3.10]), diabetes (HR, 1.73 [1.14–2.61]), incessant VT (HR, 2.96 [1.74–5.03]), linear lesion (HR, 1.46 [0.99–2.16]), and acute procedural failure (HR, 2.57 [1.39–4.77]). Procedural failure was the only statistically significant predictor for VT recurrence during follow‐up (HR, 3.76 [1.59–8.91]).

Conclusions
Within an all‐comer patient cohort, estimated 10‐year all‐cause mortality following VT ablation is 39.4%. Mortality after VT ablation is worse in patients with SHD and highest for patients with ischemic heart disease. Acute procedural success plays a major role in predicting VT recurrence and long‐term mortality.
Pericytes and Extracellular Vesicle Interactions in Neurovascular Adaptation to Chronic Arterial Hypertension
Authors: Morton Lorena , Garza Alejandra P. , Debska‐Vielhaber Grazyna , Villafuerte Luis E. , Henneicke Solveig , Arndt Philipp , Meuth Sven G. , Schreiber Stefanie , Dunay Ildiko R. 
Published: December 2024

Background
Chronic arterial hypertension restructures the vascular architecture of the brain, leading to a series of pathological responses that culminate in cerebral small‐vessel disease. Pericytes respond dynamically to vascular challenges; however, how they manifest under the continuous strain of hypertension has not been elucidated.

Methods and Results

In this study, we characterized pericyte behavior alongside hypertensive states in the spontaneously hypertensive stroke‐prone rat model, focusing on their phenotypic and metabolic transformation. Flow cytometry was used to characterize pericytes by their expression of platelet‐derived growth factor receptor β, neuroglial antigen 2, cluster of differentiation 13–alanyl aminopeptidase, and antigen Kiel 67. Microvessels were isolated for gene expression profiling and in vitro pericyte expansion. Immunofluorescence validated the cell culture model. Plasma‐derived extracellular vesicles from hypertensive rodents were applied as a treatment to assess their effects on pericyte function and detailed metabolic assessments on enriched pericytes measured oxidative phosphorylation and glycolysis. Our results reveal a shift in platelet‐derived growth factor receptor β
+
pericytes toward increased neuroglial antigen 2 and cluster of differentiation 13–alanyl aminopeptidase coexpression, indicative of their critical role in vascular stabilization and inflammatory responses within the hypertensive milieu. Significant alterations were found within key pathways including angiogenesis, blood–brain barrier integrity, hypoxia, and inflammation. Circulating extracellular vesicles from hypertensive rodents distinctly influenced pericyte mitochondrial function, evidencing their dual role as carriers of disease pathology and potential therapeutic agents. Furthermore, a shift toward glycolytic metabolism in hypertensive pericytes was confirmed, coupled with ATP production dysregulation.

Conclusions
Our findings demonstrate that cerebral pericytes undergo phenotypic and metabolic reprogramming in response to hypertension, with hypertensive‐derived plasma‐derived extracellular vesicles impairing their mitochondrial function. Importantly, plasma‐derived extracellular vesicles from normotensive controls restore this function, suggesting their potential as both therapeutic agents and precision biomarkers for hypertensive vascular complications. Further investigation into plasma‐derived extracellular vesicle cargo is essential to further explore their therapeutic potential in vascular health.
Faith in the Balance: ASEAN’s Quest for Religious Freedom Amidst Cultural Diversity
Authors: Wahid Ratnaria 
Published: December 2024

Abstract
This article examines the challenges ASEAN countries face in safeguarding Freedom of Religion or Belief (FoRB) within diverse cultural contexts. Using a qualitative approach, it first reviews international and regional frameworks to explore how ASEAN nations balance FoRB commitments with national sovereignty, revealing tensions between global standards and regional autonomy. It then compares constitutional protections across ASEAN, identifying themes in shared principles and varied implementations. The analysis identifies concerns hampering FoRB, including state religion designations, conditional protections, and discrepancies between constitutional ideals and practice. Issues like state involvement in religious practices, challenges to pluralism in single-faith societies, and diverse institutional strategies for FoRB oversight underscore the complexities involved. These findings suggest that the effective preservation of FoRB requires a nuanced approach that honours national sovereignty while safeguarding individual liberties.
Microsimulation Estimates of Decision Uncertainty and Value of Information Are Biased but Consistent
Authors: Goldhaber-Fiebert Jeremy D. , Jalal Hawre , Alarid-Escudero Fernando 
Published: December 2024

Purpose Individual-level state-transition microsimulations (iSTMs) have proliferated for economic evaluations in place of cohort state transition models (cSTMs). Probabilistic economic evaluations quantify decision uncertainty and value of information (VOI). Previous studies show that iSTMs provide unbiased estimates of expected incremental net monetary benefits (EINMB), but statistical properties of iSTM-produced estimates of decision uncertainty and VOI remain uncharacterized. Methods We compare iSTM-produced estimates of decision uncertainty and VOI to corresponding cSTMs. For a 2-alternative decision and normally distributed incremental costs and benefits, we derive analytical expressions for the probability of being cost-effective and the expected value of perfect information (EVPI) for cSTMs and iSTMs, accounting for correlations in incremental outcomes at the population and individual levels. We use numerical simulations to illustrate our findings and explore the impact of relaxing normality assumptions or having >2 decision alternatives. Results iSTM estimates of decision uncertainty and VOI are biased but asymptotically consistent (i.e., bias approaches 0 as number of microsimulated individuals approaches infinity). Decision uncertainty depends on 1 tail of the INMB distribution (e.g., P[INMB <0]), which depends on estimated variance (larger with iSTMs given first-order noise). While iSTMs overestimate EVPI, their direction of bias for the probability of being cost-effective is ambiguous. Bias is larger when uncertainties in incremental costs and effects are negatively correlated since this increases INMB variance. Conclusions iSTMs are useful for probabilistic economic evaluations. While more samples at the population uncertainty level are interchangeable with more microsimulations for estimating EINMB, minimizing iSTM bias in estimating decision uncertainty and VOI depends on sufficient microsimulations. Analysts should account for this when allocating their computational budgets and, at minimum, characterize such bias in their reported results. Highlights Individual-level state-transition microsimulation models (iSTMs) produce biased but consistent estimates of the probability that interventions are cost-effective. iSTMs also produce biased but consistent estimates of the expected value of perfect information. The biases in these decision uncertainty and value-of-information measures are not reduced by more parameter sets being sampled from their population-level uncertainty distribution but rather by more individuals being microsimulated for each parameter set sampled. Analysts using iSTMs to quantify decision uncertainty and value of information should account for these biases when allocating their computational budgets and, at minimum, characterize such bias in their reported results.
Fracture Compression and Construct Stability with Variable Pitch Locking Screws in Cadaveric Specimens
Authors: Koroneos Zachary A. , Alwine Shelby , Tortora Peter , Pitcher Michaela D. , Benedict Christian , Wee Hwabok , Kunselman Allen , Lewis Greg , Aynardi Michael 
Published: December 2024

Category: Trauma; Basic Sciences/Biologics Introduction/Purpose: A variable pitch locking screw is intended to provide interfragmentary compression combined with fixed angle stability of locking plate constructs. The objective of this study was to compare variable pitch locking screws with standard locking screws in bicortical fixation scenarios in cadaver bone, by assessing: (1) interfragmentary compression and plate-bone compression; and (2) construct biomechanical stability. Methods: Nine matched pairs of fresh-frozen cadaveric specimens were used to compare variable pitch locking screws and standard locking screws. First, interfragmentary compression and plate-bone compression associated with insertion of single bicortical screws at increasing levels of torque were measured in distal tibiae having a simulated longitudinal fracture. Second, fibulae were osteotomized to create a stable fracture pattern, fixed with five-screw plated constructs, and tested in either cyclic axial and torsional loading or four-point bending. Results: Interfragmentary and plate-bone compression forces were significantly higher with variable pitch locking screws compared to standard locking screws (p =0.002 & p=0.028, respectively). The amount of compression was variable across specimens. In cyclic loading of fibula constructs, no significant differences were detected in construct axial displacement or angular displacement. In four-point bending, no differences were detected in maximum force or bending stiffness. Conclusion: Variable pitch locking screws can produce high interfragmentary compression between cortices, along with moderate plate-bone compression. In a stable bicortical fixation scenario under external loading, construct stability was similar to normal locking screws.
Heatmaps on Radiological Safety in Minimally Invasive Midfoot Fusion: A Cadaver Study
Authors: Karaismailoglu Bedri , Peiffer Matthias , Raduan Fernando , Hollander Julian , Knebel Ashley , Kwon John Y. , Bejarano-Pineda Lorena , Ashkani-Esfahani Soheil , Miller Christopher P. 
Published: December 2024

Category: Midfoot/Forefoot Introduction/Purpose: The popularity of minimally invasive (MIS) techniques in foot and ankle surgery continues to grow exponentially. However, it comes with certain limitations that present notable challenges. One significant hurdle is the absence of direct visualization of neurovascular structures and tendons. This study aims to present fluoroscopic heatmaps that illustrate the trajectories of major structures encountered during MIS midfoot procedures. Methods: Sequential dissection was performed on nine below-knee specimens identifying the following anatomy structures: anterior tibialis tendon (ATT), extensor hallucis tendon (EHL), extensor digitorum longus tendon (EDL), superficial peroneal nerve (SPN) and dorsal neurovascular bundle (DNVB). Subsequently, flexible wires were positioned and securely placed adjacent to the medial and/or lateral borders of these structures to visualize their trajectories on X-ray imaging. Anteroposterior (AP) and oblique fluoroscopy images of the foot, featuring a calibration marker of a known diameter, were taken, alongside macroscopic photos. All fluoroscopy images were adjusted to a uniform scale and standardized to a single foot fluoroscopy. The coordinates of the structures were marked on these standardized foot AP and oblique fluoroscopy views. These coordinates were then inputted into a custom-made Python script to generate heatmaps. Results: Successfully generated heatmaps encompassed the DNVB, ATT, EDL, EHL, and SPN, on AP and oblique fluoroscopy images of the foot. The color gradient used visually represents varying magnitudes, with red indicating the most frequent locations of the structures and blue signifying lower occurrences. These heatmaps also illustrate the highest-risk areas for iatrogenic injury to the structures during MIS procedures. Conclusion: This study can empower surgical navigation and improve safety in MIS midfoot procedures by providing surgeons with a fluoroscopic heatmap detailing the trajectories of major anatomical structures.
Isolated Syndesmotic Fixation is Associated with Increased Risk of Arthrodesis and Arthroplasty Operations Compared to Nonoperatively Managed Syndesmotic Injury: A Propensity-Scored Analysis
Authors: Sequeira Sean , Gould Heath P. , Hembree Walter C. 
Published: December 2024

Category: Trauma; Sports Introduction/Purpose: Disruption of the distal tibiofibular syndesmosis can occur concomitantly with ankle fracture or as an isolated soft tissue injury. Although syndesmotic fixation is effective in providing stability to the distal tibiofibular joint, biomechanical studies suggest that over-reduction of the syndesmosis may increase ankle contact pressures and potentially accelerate tibiotalar joint degeneration in the longer term. The purpose of this investigation was to evaluate reoperation rates in patients with isolated syndesmotic disruption who underwent fixation versus those who were managed nonoperatively. Methods: A large, nationwide insurance database was retrospectively reviewed to identify all patients who were diagnosed with an isolated distal tibiofibular syndesmotic injury (without concomitant fracture) between 2010 and 2019. Patients who underwent surgical stabilization were matched using a propensity scoring algorithm to patients who were managed nonoperatively. The rates of reoperation including subsequent ankle arthroscopy, ankle arthrodesis, and total ankle arthroplasty (TAA) were compared between groups. Results: 24,758 patients who underwent operative stabilization were matched to 24,758 patients who underwent nonoperative management for syndesmotic injury. Patients who underwent surgical stabilization had an increased risk of ankle arthrodesis (4.04; p< 0.001) and TAA (OR 3.11; p< 0.001) within ten years compared to patients managed nonoperatively. There was no difference between groups with regard to the comparative risk of subsequent ankle arthroscopy within five years. Conclusion: Patients with isolated syndesmotic injury who underwent operative stabilization were more likely to require an ankle arthrodesis or total ankle arthroplasty within 10 years compared to those who were managed nonoperatively. These findings in a large, propensity-matched cohort suggest that surgeons should consider the implications of syndesmotic over-reduction when managing these injuries intraoperatively. Moreover, surgeons may incorporate these data into the decision making process when counseling patients regarding the expected outcomes of operative and nonoperative management for syndesmotic injury.
Lateral Column Pressures Following Combined Subtalar/Talonavicular Fusion with and without Calcaneocuboid Fusion
Authors: Alkaramany Eslam , Gallagher Brian P. , Abbasi Pooyan , Guyton Gregory P. 
Published: December 2024

Category: Hindfoot; Other Introduction/Purpose: There are few comparative studies between the traditional triple arthrodesis and the commonly performed modified procedure in which the calcaneocuboid joint is spared. Earlier investigations proposed that stiffening the lateral column of the hindfoot can increase lateral plantar pressures, potentially precipitating lateral column pain. We used a cadaver model to quantify the potential for reduced lateral column overload achieved by sparing the calcaneocuboid joint in a cadaveric model of triple arthrodesis simulating standing on both a neutral and sloping surface. Methods: Nine fresh-frozen, thawed cadaver legs were tested in 2 positions of the loaded surface: neutral and 10 degrees of eversion. Tendon loading and axial pressure was applied according to standard cadaveric models. Medial and lateral forefoot pressures were recorded using a pressure-sensitive plate (F-scan). The data were normalized as a percentage of the native state. Results: In neutral loading, the mean contact pressures under the fifth metatarsal head increased dramatically compared to the native state in both the standard (76.3%, p<.005) and calcaneocuboid-sparing (103.5%, p<.007) procedures. Pressure was reduced underneath the first metatarsal head medially in both standard (-52.8%, p< 0.017) and calcaneocuboid-sparing (-57.2%, p< 0.008). Loading on an everted surface yielded larger overall pressures laterally, but the further increases compared to the native state following both standard (39.0%, p < 0.04) and calcaneocuboid-sparing (57.9%, p< 0.03) procedures were smaller than in the neutrally loaded foot. No statistically significant difference was observed between the arthrodesis groups when loaded either on a neutral or sloped surface. Conclusion: In our cadaveric model, both traditional triple arthrodesis and the calcaneocuboid-sparing procedure resulted in significant elevation of lateral forefoot plantar pressures compared to the native state, but there was no identifiable protective effect from sparing the calcaneocuboid joint even in the provocative condition of loading on a sloping surface. Clinical Relevance: While other factors may guide the choice to spare the calcaneocuboid joint when performing hindfoot fusion, there is no evidence that preserving its motion significantly reduces the risk of lateral column overload.
Low Rates of Return to Sport and Reduction in Performance Following Ankle Fractures in Elite Rugby Union Players
Authors: Butler James J. , Calton Megan , Greene Allison , Rosenbaum Andrew , Mulligan Michael , Kennedy John G. 
Published: December 2024

Category: Trauma; Ankle Introduction/Purpose: The purpose of this study was to assess outcomes following ankle fractures sustained by elite rugby union players. Methods: Elite rugby union players who sustained an ankle fracture were identified using a publicly available database, match reports and injury reports. "Elite rugby union" was defined as a player who played professional rugby in the following competitions: United Rugby Championship, Top 14, English Premiership, Super Rugby and international rugby for a top 20 ranked team. The years of inclusion was from 2015-2022. Data collected and analysed: player demographics, player position, if surgical intervention was warranted, rates of return to play (RTP), time to return to play, games missed. Pre-injury and post-injury performance outcomes collected and analysed: games played, tries scored, points scored. Results: 107 elite rugby union players sustained an ankle fractures between 2014-2022 (0.0186 per 10,000 athlete-exposures). The mean age was 24.2±9.1 years and the mean BMI was 31.8±8.9kg/m2. There were 71 (61.3%) ankle fractures sustained by forwards and 36 (33.6%) ankle fractures sustained by backs. Ninety (84.1%) ankle fractures occurred during the in-season and 17 (15.9%) ankle fractures occurred during training. All athletes (100%) underwent surgical intervention. The most common mechanism of injury was direct trauma to the ankle during a tackle (55.9%). The RTP rate was 78.3% at mean time of 8.9±3.9 months. There was a statistically significant decrease in the mean number of games played, tries scored and points scored following RTP. Conclusion: This current study found that ankle fractures were an uncommon injury in elite rugby union players with an incidence of 0.0186 per 10,000 athlete-exposures. Sustaining an ankle fracture was associated with a RTP rate of 78.3% at mean time of 8.9±3.9 months. There was a statistically significant deterioration in key performance metrics such as mean games played, tries scored and points scored. This study reinforces the potentially devastating sequelae following ankle fractures in the elite athletic population.