bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient Preferences for Features Associated With Leadless Versus Conventional Transvenous Cardiac Pacemakers
Authors: Reed Shelby D. , Yang Jui-Chen , Wallace Matthew J. , Sutphin Jessie , Johnson F. Reed , Ozdemir Semra , Delgado Stephanie M. , Goates Scott , Harbert Nicole , Lo Monica , Rajagopalan Bharath , Ip James E. , Al-Khatib Sana M.
Published: November 2024

BACKGROUND:

Regulatory approval of the first dual-chamber leadless pacemaker system provides patients an alternative to conventional transvenous pacemakers. The study objective was to quantify the preferences of patients for pacemaker features.

METHODS:

Patients with a de novo (ie, initial) pacemaker indication were recruited from 7 US sites to complete a Web-based discrete-choice experiment survey between May 11, 2022, and May 24, 2023. Patients chose between pairs of experimentally designed, hypothetical pacemakers that varied according to type (removable leadless, nonremovable leadless, or conventional transvenous); battery life (5, 8, 12, or 15 years); time since regulatory approval (2 or 10 years); discomfort for 6 months (none or discomfort); and complication risk and infection risk (1%, 5%, or 10%/20% for each). Patients’ choice data were analyzed using random-parameter logit models and latent-class analysis.

RESULTS:

Among 117 participants, the mean (SD) age was 67.3 (14.6) years, 94% were white, and 42% were female. On average, patients’ survey responses revealed a preference for removable leadless pacemakers (β, 0.340; SE, 0.096) over both nonremovable leadless pacemakers (β, −0.310; SE, 0.131;
P
=0.001) and conventional transvenous pacemakers (β, −0.030; SE, 0.119;
P
=0.031). However, latent-class analysis revealed 2 distinct preference classes. One class preferred leadless pacemakers (50.5%), and the other class preferred conventional transvenous pacemakers (49.5%). The conventional pacemaker class prioritized pacemakers with 10 rather than 2 years since regulatory approval (
P
<0.001), whereas the leadless pacemaker class was insensitive to years since regulatory approval (
P
=0.83). Complication risks and infection risks were found to be the most influential. All else equal, patients would accept maximum risks of complications or infections ranging about 5% to 18% to receive their preferred pacemaker type.

CONCLUSIONS:

Latent-class analysis revealed strong patient preferences for the type of pacemaker, with a nearly equal split between recent leadless pacemaker technology and conventional transvenous pacemakers. These findings can inform shared decision-making between health care providers and patients.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT05327101.
A Latent Cardiomyocyte Regeneration Potential in Human Heart Disease
Authors: Derks Wouter , Rode Julian , Collin Sofia , Rost Fabian , Heinke Paula , Hariharan Anjana , Pickel Lauren , Simonova Irina , Lázár Enikő , Graham Evan , Jashari Ramadan , Andrä Michaela , Jeppsson Anders , Salehpour Mehran , Alkass Kanar , Druid Henrik , Kyriakopoulos Christos P. , Taleb Iosif , Shankar Thirupura S. , Selzman Craig H. , Sadek Hesham , Jovinge Stefan , Brusch Lutz , Frisén Jonas , Drakos Stavros , Bergmann Olaf
Published: November 2024

BACKGROUND:

Cardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate of ≈0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial.

METHODS:

We determined cardiomyocyte renewal in 52 patients with advanced heart failure, 28 of whom received left ventricular assist device support. We measured the concentration of nuclear bomb test–derived
14
C in cardiomyocyte genomic DNA and performed mathematical modeling to establish cardiomyocyte renewal in heart failure with and without LVAD unloading.

RESULTS:

We show that cardiomyocyte generation is minimal in end-stage heart failure patients at rates 18 to 50× lower compared with the healthy heart. However, patients receiving left ventricle support device therapy, who showed significant functional and structural cardiac improvement, had a >6-fold increase in cardiomyocyte renewal relative to the healthy heart.

CONCLUSIONS:

Our findings reveal a substantial cardiomyocyte regeneration potential in human heart disease, which could be exploited therapeutically.
Association of Coagulation Factor XI Level With Cardiovascular Events and Cardiac Function in Community-Dwelling Adults: From ARIC and CHS
Authors: Ji Yuekai , Zhang Michael J. , Wang Wendy , Norby Faye L. , Eaton Anne A. , Inciardi Riccardo M. , Alonso Alvaro , Sedaghat Sanaz , Ganz Peter , Van’t Hof Jeremy , Solomon Scott D. , Chaves Paulo H.M. , Heckbert Susan R. , Shah Amil M. , Chen Lin Yee
Published: November 2024

BACKGROUND:

Coagulation factor XI (FXI) inhibitors are a promising and novel class of anticoagulants, but a recent animal study found that FXI inhibition exacerbated diastolic dysfunction and heart failure (HF). In the ARIC study (Atherosclerosis Risk in Communities), we investigated whether plasma FXI level was associated with cardiovascular events and cardiac function.

METHODS:

ARIC was our primary analytic cohort. We included 4471 participants (median age, 75 years; 57% female; 17% Black) who attended visit 5 (2011–2013) with Somalogic-quantified plasma FXI levels and echocardiographic cardiac function. Prevalent HF and atrial fibrillation (AF) cases were defined as having HF or AF diagnosed at or before each participant’s visit 5 exam date. Incident HF and AF events were ascertained through 2021. Associations were assessed using Cox, logistic, and linear regression models. Primary prospective associations were also validated in the CHS (Cardiovascular Health Study) using an orthogonal FXI assay (enzyme-linked immunosorbent assay).

RESULTS:

At ARIC visit 5, there were 665 and 419 participants with prevalent HF and AF, respectively. During a median follow-up of 9 years, there were 580 and 788 incident HF and AF events, respectively. Lower FXI level was associated prospectively with higher incidence of HF (hazard ratio [HR], 1.36 [for each 1-unit decrement of log
2
-transformed FXI level] [95% CI, 1.01–1.83]) but not incident AF, and cross-sectionally with increased odds of AF (odds ratio [OR], 1.96 [95% CI, 1.23–3.07]) but not HF. In age-stratified analyses, decreased FXI was associated with higher incidence of HF in participants ≥75 years of age (HR, 1.57 [95% CI, 1.08–2.28]) but not <75 years of age (HR, 1.11 [95% CI, 0.68–1.79]). The inverse FXI–HF association was validated in CHS (HR, 1.18 [95% CI, 1.02–1.36]). At ARIC visit 5, lower FXI level was also associated with higher prevalence of diastolic dysfunction and worse E/A ratio, left atrial (LA) volume index, LA function, and left ventricular mass index, but not left ventricular ejection fraction or global longitudinal strain.

CONCLUSIONS:

Decreased FXI level is associated with greater incidence of HF, especially in older adults. It is also associated with prevalent AF, worse diastolic function, worse LA function, and greater LA size. More research is needed to assess potential unwanted effects of FXI inhibition on the risk of cardiovascular events and cardiac function.
A comparison of extraction methods for preparation of glucosinolate-containing extracts from Brassica juncea antagonistic toward Ditylenchus dipsaci
Authors: Temiz Mehmet A. , Aksay Gamze , Özcan Ali , Yavuzaslanoğlu Elif
Published: November 2024

The stem and bulb nematode, a globally distributed pest, primarily affects onions and garlic, causing significant yield losses. Chemical treatments are a practical and effective method for controlling plant-parasitic nematodes to protect high-value crops. However, to minimise environmental damage, chemicals of natural origin need to be investigated. Brown mustard (Brassica juncea) plant is an annual plant in the Brassicaceae family, which is rich in bioactive compounds called glucosinolates. These bioactive compounds play a major role in the defence of Brassica plants against biotic stress factors in nature. Based on this point, efforts to develop plant protection products from the brown mustard plant are ongoing. In this study, the most suitable pre-extraction and extraction conditions were determined to ensure the maximum preservation of glucosinolate content and biological activity, to process brown mustard on an industrial scale. For this purpose, steam treatment was applied before extraction at 3 bar (=3 × 105 Pa) pressure for 1 and 3 min. Four different temperatures (room temperature, 40, 55 and 70°C) and two different methanol concentrations (70% and 80%) were tested to optimise glucosinolates extraction from brown mustard. It was found that sinigrin was the most abundant glucosinolate, with extraction yields 1184.4 ± 14.4 mg kg−1 at 55°C for 3 min, and 2624.2 ± 98.5 mg kg−1 at 70°C/70% MeOH for 1 min. However, nematode immobility was higher at 55°C/70% MeOH for 3 min. It was determined that the application of hot steam for 3 min at 3 bar pressure as a pre-extraction process provided optimal conditions for methanolic extraction. The results may contribute significantly to the development of potential plant protection products with further studies.
Regulating Land in Rural Africa: An Institutional, Vulnerability Perspective
Authors: Viljoen Sue-Mari
Published: November 2024

Recent scholarship has focused on socio-economic trends concerning rural degradation, urbanisation and the sustainable use of natural resources. This article draws on these studies to focus on rural Africa, its projected poverty levels, and the institutional role in relation to these estimates. It uses vulnerability theory, progressive property theory and resilient property theory to reframe rural property as an asset of resilience for both communities and the state, arguing that property is being institutionalized across rural Africa to serve political interests, backed by global demands, at the cost of local communities, and their resiliency needs.
L’idée du califat au Maroc (VIIIe-XVIIIe siècles)
Authors: Mouline Nabil
Published: November 2024

This article explores the evolution of the concept of caliphate in Morocco from the 8th to the 17th century, highlighting its usage by diverse local actors and social groups to break free from foreign influence, legitimize their authority, consolidate power, and occasionally pursue imperial aspirations. We argue that this form of universal monarchy paradoxically influenced the territorial, political, and religious development of classical Morocco.
L’adieu au califat ?
Authors: Moreau Odile
Published: November 2024

Since the revolutionary period of the “Arab Spring”, which began in 2011, the question of the Caliphate and its persistence has been the subject of renewed interest, due to new forms of expression of the Caliphate. Implicit in this is the question of its evanescence. When, on 3 March 1924, the Turkish Grand National Assembly in Ankara voted to abolish the caliphate, shockwaves swept through the Muslim world. Our contribution looks at the contextualisation of this decision, which in a way took on a ‘revolutionary’ dimension in a Middle Eastern scene undergoing profound reconfiguration. We will highlight the dynamics at work, and how this decision was part of the genealogy of institutional changes in the Ottoman Empire, in successive strata. After the abolition of the sultanate on 1 November 1922, the dual title of sultan-caliph disappeared, leaving the caliphate in potential remission.
Female Patients and Staff at Hanwell Asylum (1830s–1860s): Negotiating Limitations and Opportunities in a Male-dominated Medical Sphere
Authors: Dubois Laurence
Published: November 2024

Hanwell Lunatic Asylum is widely recognised as having been emblematic of Victorian British asylums, for which it represented a therapeutic model. It was nevertheless a relatively atypical institution in its way of treating male and female patients, and this was in no small part due to the personality of John Conolly, its medical superintendent from 1839 to 1852. His political convictions, deeply rooted in utopian socialism, made him less inclined to conform to middle- and upper-class social norms of the time, which tended to limit women in their social and intellectual aspirations. More typical was the undeniable tendency in the institution to strictly separate the male and female spheres, the medical profession having long been a field traditionally reserved to men. The situation was nevertheless quite different within what might be called the “social sphere” of the asylum. Here female staff played a key role, under the authority of the matron. This paper will seek to demonstrate that, despite genuine restrictions and limitations imposed on female patients and nurses – many of which were in fact imposed on both genders, and were denounced by female staff and chaplains – the asylum could nevertheless appear as a safe place for women to gain access to education, leisure and social interactions, and could even offer them some kinds of professional opportunities.
Commons-Based Memories: Programming Practices and Large Language Models
Authors: Depaz Pierre
Published: November 2024

This article examines the role of digital interfaces in the creation and access of productive memory in the context of programming communities of practice. We first propose an analysis of question-and-answer platforms as the dominant means of creating such memories, and how such technical environment results in the constitution of knowledge commons. We then contrast these means with the emergence of programming-focused large language models, and how they represent a shift from large collaborative environment to non-human collaboration. As a result, we draw some implications regarding the sustainability of knowledge commons as well as the complementarity of digital devices in affecting the knowledge and values of the collective memories of programmers.
Knowledge
Authors: Weatherson Brian
Published: November 2024

In this book the author argues for a groundbreaking perspective that knowledge is inherently interest-relative. This means that what one knows is influenced not just by belief, evidence, and truth, but crucially by the purposes those beliefs serve. Drawing from classical Nyāya epistemologies, the book asserts that knowledge rationalizes action: if you know something, it is sensible to act on it—and the best way to square this with an anti-sceptical epistemology is to say that knowledge is interest-relative.

While versions of this view have been debated, they haven’t gained wide acceptance. The author addresses common objections with a refined formulation and explores how this perspective elucidates the role of knowledge in inquiry, daily life, and the history of thought. Key distinctions include the impact of “long odds” situations on knowledge, the distinctive role knowledge has a starting point for inquiry, and the importance of using non-ideal models in theorising about knowledge.

Building on decades of scholarship, the author offers a cohesive theory that integrates and clarifies previous works, demonstrating that not only knowledge but also belief, rational belief, and evidence are interest-relative. This book is essential for those seeking a deeper understanding of the intricate relationship between knowledge and practical interests.
1. Overture
Authors: Weatherson Brian
Published: November 2024

This chapter summarises the themes of the book, with an emphasis on how they connect to some infrequently discussed events in the history of philosophy. In particular, it discusses how the idea that what knows varies depending on what one is inquiring into interacts with these four events. First, the idea from late Ancient sceptics such as Philo of Larissa that scepticism needs to be paired with a notion of when something can sensibly taken for granted in everyday life. Second, the medieval discussions of when a jurist will be forgiven in the afterlife if they have sentenced an innocent person. Third, the early modern discussions of what standards should be applied to publishing in the new invention: the scientific journal. And fourth, the classical Nyāya arguments that respond to the sceptic by highlighting the practical role of knowledge. The aim here is to suggest an alternative way of looking at the history of epistemology, one that makes the practicality of knowledge central to the story.
10. Power
Authors: Weatherson Brian
Published: November 2024

This chapter ends the book with a short note connecting interest-relativity to the familiar saying Knowledge is Power. I argue that this saying only makes sense on an interest-relative view of knowledge. If interest-relative theories were flawed for one reason or another, then we’d have to simply concede that the saying is false. But we shouldn’t concede that; the saying is true, and interest-relative epistemology explains why it is true.
Wielojęzyczność migrantów wojennych z Ukrainy w Polsce
Authors: Levchuk Paweł
Published: November 2024

Russia’s invasion of Ukraine resulted in the migration to Poland of about 10 million Ukrainians: after 24 February 2022 they stayed here for some time or settled in the country for good. This book investigates their language behaviours and preferences. The theoretical part outlines the issues of migration of Ukrainians to Poland in 2022, which was the sixth wave of migration, by far larger than all previous ones combined. This part also considers social and cultural aspects of the arrival and stay of Ukrainians in Poland. The first chapter is devoted to a discussion of the research apparatus applied in the study of multilingualism and language contact, and their impact on the current language situation of this large group of migrant population in Poland. The chapter also presents the research methodology and the adaptation of research concepts applied in previous studies. Chapter 2 describes the struggle of tsarist Russia and then the Soviet Union against the Ukrainian language. The third chapter outlines the political and linguistic situation in 2019–2022 and current research on the issue of the presence of Ukrainians in Poland. Chapters 4, 5 and 6 are devoted to a discussion of the survey results, arranged according to three categories of respondents distinguished in the study (U – respondents whose first language is Ukrainian; R – respondents whose first language is Russian; UR – respondents who have two first languages: Ukrainian and Russian). The study was conducted between April and July 2022, and the number of those who took part was 1,503. The following issues were examined: the identity of the respondents, the frequency of their use of each language, their emotional attitudes to them, the interlocutors and the places of interactions in each language. Other issues in focus included the respondents’ attitudes towards Polish and their plans concerning this language and Poland. Chapter 7 presents the models of language behaviours of war migrants from Ukraine developed on the basis of the study, which are structured into a matrix of their multilingualism. The eighth chapter, in turn, is devoted to their language biographies and the changes in their attitudes towards each of the languages following the Russian invasion and before it. The findings of the study could provide valuable insights for policymakers to enhance Polish-Ukrainian cooperation and language policy in Ukraine.
Air Quality Warning and Integrated Decision Support System for Emissions (AIRWISE): Enhancing Air Quality Management in Megacities
Authors: Ghude Sachin D. , Govardhan Gaurav , Kumar Rajesh , Yadav Prafull P. , Jat Rajmal , Debnath Sreyashi , Kalita Gayatri , Jena Chinmay , Ingle Shubhangi , Gunwani Preeti , Pawar Pooja V. , Ambulkar Rupal , Kumar Sumit , Kulkarni Santosh , Kulkarni Akshay , Khare Manoj , Kaginalkar Akshara , Soni V. K. , Nigam Narendra , Ray Kamaljit , Atri S. D. , Nanjundiah Ravi , Rajeevan M.
Published: November 2024

Air pollution poses a significant environmental risk to large cities worldwide, including New Delhi, India’s capital. The occurrence of frequent episodes of elevated levels of air pollution during October–March in Delhi and National Capital Territory (Delhi–NCT) chokes its ∼32 million residents every year. Current air quality models lack the ability to accurately predict severe air pollution events in Delhi–NCT, rendering decision-makers helpless in their efforts to safeguard public health. To address this, a new initiative introduced a high-resolution Air Quality Early Warning System (AQEWS) in 2018, followed by the integration of a decision support system (DSS) in 2021. This enhancement enables dynamic source attribution data and diverse emission reduction scenarios within a single model forecast. The newly developed system, Air Quality Warning and Integrated Decision Support System for Emissions (AIRWISE), assimilates near-real-time satellite aerosol optical depth (AOD) retrievals, satellite-based fire information, surface data from 320 air quality monitoring stations, and high-resolution emissions, resulting in an extensive modeling framework. This framework demonstrates exceptional prediction capabilities, accurately forecasting very poor air quality episodes up to 3 days in advance with a remarkable 83% accuracy, even at a street-level resolution of 400 m. The AQEWS is the world’s first operational air quality forecasting system operating at a high resolution and incorporating chemical data assimilation. The Commission for Air Quality Management (CAQM) relies on forecast data to enforce the Graded Response Action Plan (GRAP) in Delhi–NCT, which imposes restrictions on pollution sources. This paper outlines the AQEWS and DSS, summarizes modeling experiments, verifies forecasts, and discusses challenges in accurately predicting extreme pollution episodes.
The filterability of leukocytes in undiluted blood
Authors: Cook A.M. , Evans S.‐A. , Jones J.G.
Published: November 2024

A filtrometer is described for measuring the flow of fluids through microfilters. The flow of Newtonian fluids through the filters can be predicted from the diameter, length and number of pores. There are no physical artefacts such as turbulent flow or a significant lag period before steady‐state flow is achieved. The instrument has been used as a viscometer and has been used to record and analyse the flow of undiluted blood through 5 $\mu$ m polycarbonate filters. The calculated viscosity of Newtonian fluids agrees well with those measured by a more conventional viscometer (Ostwald). Flow profiles of blood have been analysed to give both the numbers and the flow properties of a small population of slow leukocytes which equate numerically with the monocytes. They are subdivided into three distinct sub‐populations, according to their rheological properties, and these are termed $\mathit{SL}_{1}$ , $\mathit{SL}_{2}$ and $\mathit{PB}$ . The concentration of these cells, in blood, are $0.12\pm0.02 \times 10^{6}$ ml $^{-1}$ , $0.11\pm0.02 \times 10^{6}$ ml $^{-1}$ , $0.09\pm0.02 \times 10^{6}$ ml $^{-1}$ in young females aged about 25 years. The transit time of these cells, through 5 $\mu$ m pores, is $34.8\pm1.4$ s, $147.5\pm2.5$ s and $> 300$ s, respectively. Analysis of blood from older men (53–79 years) gives essentially the same results although the concentration of $SL_{1}$ is slightly higher at $0.19\pm0.09 \times 10^{6}$ ml $^{-1}$ .
Hyaluronan, hydration and flow conductivity of rat dermis
Authors: Bert Joel , Reed Rolf K.
Published: November 2024

We have measured the flow conductivity, $k/\eta$ , of discs of rat dermis with and without digestion with hyaluronidase. We found no significant difference between the flow conductivity of hyaluronan digested ( $k/\eta=5.56\pm2.74$ cm $^{4}$ /dyne.s ( $n=13$ )) and untreated tissue ( $k/\eta=6.03\pm3.15$ cm $^{4}$ /dyne.s ( $n=13$ )). For the first time in such experiments the overall tissue hyaluronan content as well as the difference in concentration of this material across tissues subjected to conditions of flow was measured. Similarly, the overall hydration and the difference in fluid content across the tissue is also reported. We have demonstrated that approximately 99% of the tissue hyaluronan was digested as a result of activity of the enzyme. No difference in hyaluronan across the tissue was found in the flow experiments (i.e., with or without digestion). We found significant change in the overall tissue hydration for controls and for either of the two types of flow experiments performed. Likewise, we found significant hydration differences across the tissues under both types of flow conditions. A trend in decreasing hydration associated with digestion of hyaluronan in the flow experiments was found.
A model for cytoplasmic rheology consistent with magnetic twisting cytometry
Authors: Butler J.P. , Kelly S.M.
Published: November 2024

Magnetic twisting cytometry is gaining wide applicability as a tool for the investigation of the rheological properties of cells and the mechanical properties of receptor–cytoskeletal interactions. Current technology involves the application and release of magnetically induced torques on small magnetic particles bound to or inside cells, with measurements of the resulting angular rotation of the particles. The properties of purely elastic or purely viscous materials can be determined by the angular strain and strain rate, respectively. However, the cytoskeleton and its linkage to cell surface receptors display elastic, viscous, and even plastic deformation, and the simultaneous characterization of these properties using only elastic or viscous models is internally inconsistent. Data interpretation is complicated by the fact that in current technology, the applied torques are not constant in time, but decrease as the particles rotate. This paper describes an internally consistent model consisting of a parallel viscoplastic element in series with a parallel viscoelastic element, and one approach to quantitative parameter evaluation. The unified model reproduces all essential features seen in data obtained from a wide variety of cell populations, and contains the pure elastic, viscoelastic, and viscous cases as subsets.
Nonlinear viscoelasticity of cheese
Authors: Tariq Salman , Giacomin A. Jeffrey , Gunasekaran Sundaram
Published: November 2024

Cheese viscoelasticity is commonly measured using steady uniaxial compression, steady uniaxial extension, shear and compressive creep, and stress relaxation in shear and compression. Viscoelastic properties for many cheeses have also been studied using small amplitude oscillatory shear (SAOS). However, there is little on the measurement of nonlinear viscoelastic properties. The large deformation test usually conducted on cheese to study nonlinear viscoelasticity is uniaxial compression, but this test hardly departs from linear behavior. In this work, the nonlinear viscoelasticity of four cheese varieties was studied using large amplitude oscillatory shear (LAOS). A sliding plate rheometer incorporating a shear stress transducer was used. The data were evaluated using spectral analysis, and results are presented mainly in the form of shear stress versus shear rate loops.
Swimming of spermatozoa in a linear viscoelastic fluid
Authors: Fulford Glenn R. , Katz David F. , Powell Robert L.
Published: November 2024

A modified resistive force theory is developed for a spermatozoon swimming in a general linear viscoelastic fluid. The theory is based on a Fourier decomposition of the flagellar velocity, which leads to solving the Stokes flow equations with a complex viscosity. We use a model spermatozoon with a spherical head which propagates small amplitude sinusoidal waves along its flagellum. Results are obtained for the velocity of propulsion and the rate of working for a free swimming spermatozoon and the thrust on a fixed spermatozoon. There is no change in propulsive velocity for a viscoelastic fluid compared to a Newtonian fluid. The rate of working does change however, decreasing with increasing elasticity of the fluid, for a Maxwell fluid. Thus the theory predicts that a spermatozoon can swim faster in a Maxwell fluid with the same expenditure of energy for a Newtonian fluid.
Low Reynolds number turbulence modeling of blood flow in arterial stenoses
Authors: Ghalichi Farzan , Ghalichi Farzan , Deng Xiaoyan , De Champlain Alain , Douville Yvan , King Martin , Guidoin Robert
Published: November 2024

Moderate and severe arterial stenoses can produce highly disturbed flow regions with transitional and or turbulent flow characteristics. Neither laminar flow modeling nor standard two‐equation models such as the $k$ ‐ $\varepsilon$ turbulence ones are suitable for this kind of blood flow. In order to analyze the transitional or turbulent flow distal to an arterial stenosis, authors of this study have used the Wilcox low‐ $\mathit{Re}$ turbulence model. Flow simulations were carried out on stenoses with 50, 75 and 86% reductions in cross‐sectional area over a range of physiologically relevant Reynolds numbers. The results obtained with this low‐ $\mathit{Re}$ turbulence model were compared with experimental measurements and with the results obtained by the standard $k$ ‐ $\varepsilon$ model in terms of velocity profile, vortex length, wall shear stress, wall static pressure, and turbulence intensity. The comparisons show that results predicted by the low‐ $\mathit{Re}$ model are in good agreement with the experimental measurements. This model accurately predicts the critical Reynolds number at which blood flow becomes transitional or turbulent distal an arterial stenosis. Most interestingly, over the $\mathit{Re}$ range of laminar flow, the vortex length calculated with the low‐ $\mathit{Re}$ model also closely matches the vortex length predicted by laminar flow modeling. In conclusion, the study strongly suggests that the proposed model is suitable for blood flow studies in certain areas of the arterial tree where both laminar and transitional/turbulent flows coexist.
Wall shear stress in backward‐facing step flow of a red blood cell suspension
Authors: Gijsen F.J.H. , van de Vosse F.N. , Janssen J.D.
Published: November 2024

An experimental investigation of the wall shear stress distribution downstream of a backward‐facing step is carried out. Flow in this geometry is considered to be representative of flow in large and medium sized curved arteries and bifurcations. The wall shear stress distribution was determined by measuring the deformation of a gel layer, attached to the wall downstream of the step. Speckle pattern interferometry was applied to measure the deformation of the gel layer. The measured deformation, combined with the properties of the gel layer, served as an input for a finite element solid mechanics computation to determine the stress distribution in the gel layer. The wall shear stress, required to generate the measured deformation of the gel layer, was determined from these computations.

A Newtonian buffer solution and a non‐Newtonian red blood cell suspension were used as measuring fluids. The deformation of the gel layer was determined for a Newtonian buffer solution to evaluate the method and to obtain the properties of the gel layer. Subsequently, the wall shear stress distribution for the non‐Newtonian red blood cell suspension was determined for three different flow rates.

The inelastic non‐Newtonian Carreau–Yasuda model served as constitutive model for the red blood cell suspension. Using this model, the velocity and wall shear stress distribution were computed by means of a finite element fluid mechanics computation. From the comparison between the numerical and the experimental results, it can be concluded that wall shear stresses, induced by the red blood cell suspension, can be modeled accurately by employing a Carreau–Yasuda model.
Effect of alterations in femoral artery flow on abdominal vessel hemodynamics in swine
Authors: Henderson J.M. , Aukerman J.A. , Clingan P.A. , Friedman M.H.
Published: November 2024

In support of an in vivo investigation in swine of the influence of changes in fluid dynamic wall shear on arterial macromolecular permeability, a procedure has been developed to alter the flows in the porcine posterior arterial vasculature by opening and closing a reversible arteriovenous shunt placed on one of the femoral arteries. Laparoscopic techniques were used to place appropriately modified Transonic Systems ultrasonic flow probes on both external and circumflex iliac arteries, and on the terminal aorta. Flow measurements were made prior to shunt placement, and with the shunt open and closed, to measure the influence of altered external iliac artery flow on the distribution to the infrarenal abdominal vessels. Similar experiments were carried out to relate the flow rates in the external iliac arteries to those in the femoral arteries, which are more accessible. Based on the relationships among the measured flow rates, rules have been developed to estimate the major infrarenal flows in the pig, at baseline and with the shunt opened and closed, from only the flow rates measured at the two femoral arteries.
Theoretical study on flow‐dependent concentration polarization of low density lipoproteins at the luminal surface of a straight artery
Authors: Wada Shigeo , Karino Takeshi
Published: November 2024

It is suspected that physical and fluid mechanical factors play important roles in the localization of atherosclerotic lesions and intimal hyperplasia in man by affecting the transport of cholesterol in flowing blood to arterial walls. Hence, we have studied theoretically the effects of various physical and fluid mechanical factors such as wall shear rate, diffusivity of low density lipoproteins (LDL), and filtration velocity of water at the vessel wall on surface concentration of LDL at an arterial wall by means of a computer simulation of convective and diffusive transport of LDL in flowing blood to the wall of a straight artery under conditions of a steady flow. It was found that under normal physiologic conditions prevailing in the human arterial system, due to the presence of a filtration flow of water at the vessel wall, flow‐dependent concentration polarization (accumulation or depletion) of LDL occurs at a blood/endothelium boundary. The surface concentration of LDL at an arterial wall takes higher values than that in the bulk flow in that vessel, and it is affected by three major factors, that is, wall shear rate, $\gamma_\mathrm{w}$ , filtration velocity of water at the vessel wall, ${V}_\mathrm{w}$ , and the distance from the entrance of the artery, ${ L}$ . It increases with increasing ${V}_\mathrm{w}$ and ${ L}$ , and decreasing $\gamma_\mathrm{w}$ hence the flow rate. Thus, under certain circumstances, the surface concentration of LDL could rise locally to a value which is several times higher than that in the bulk flow, or drop locally to a value even lower than a critical concentration for the maintenance of normal functions and survival of cells forming the vessel wall. These results suggest the possibility that all the vascular phenomena such as the localization of atherosclerotic lesions and intimal hyperplasia, formation of cerebral aneurysms, and adaptive changes of lumen diameter and wall structure of arteries and veins to certain changes in hemodynamic conditions in the circulation are governed by this flow‐dependent concentration polarization of LDL which carry cholesterol.
Flow‐dependent concentration polarization of plasma proteins at the luminal surface of a semipermeable membrane
Authors: Naiki Takeru , Karino Takeshi
Published: November 2024

The effect of steady shear flow on concentration polarization of plasma proteins and lipoproteins at the luminal surface of a semipermeable vessel wall was studied experimentally using suspensions of these molecules in a cell culture medium and a semipermeable membrane dialysis tube which served as a model of an implanted vascular graft or an artery. The study was carried out by flowing a cell culture medium containing fetal calf serum or bovine plasma lipoproteins or bovine albumin through a 7.5 mm diameter, 60 mm‐long dialysis tube in steady flow under a physiologic mean arterial perfusion pressure of 100 mmHg, and measuring the filtration velocity of water (cell culture medium) at the vessel wall which varied as a consequence of the change in concentration of plasma protein particles at the luminal surface of the semipermeable membrane dialysis tube. It was found that for perfusates containing plasma proteins and/or lipoproteins, filtration velocity of water was the lowest in the absence of flow, and it increased or decreased as the flow rate (hence wall shear rate) increased or decreased from a certain non‐zero value, indicating that surface concentration of protein particles varied reversibly as a direct function of flow rate. It was also found that at particle concentrations equivalent to those found in a culture medium containing serum at 5% by volume, plasma lipoproteins which were much smaller in number and lower in concentration but larger in size than albumin, had a much larger effect on the filtration velocity of water than albumin. These findings were very much the same as those previously obtained with a cultured endothelial cell monolayer, strongly suggesting that the flow‐dependent variation in filtration velocity of water at a vessel wall results from a physical phenomenon, that is, flow‐dependent concentration polarization of low density lipoproteins at the luminal surface of the endothelial cell monolayer.
Influence of fibrinogen and haematocrit on erythrocyte sedimentation kinetics
Authors: Holley Loraine , Woodland Narelle , Hung Wai Tak , Cordatos Katherine , Reuben Andreas
Published: November 2024

This study investigates the influence of haematocrit, fibrinogen concentration and fibrinogen availability (amount of fibrinogen per red blood cell) on erythrocyte sedimentation. The Westergren technique was applied to blood samples from 36 subjects and to their blood manipulated to haematocrits of 10, 20, 30 and 40%. Readings were taken every 10 minutes for 300 minutes. Previous studies indicate that erythrocyte sedimentation occurs in three phases. In this study, we show that haematocrit has little influence on either the rate of fall of particles in the first phase ( $m_{1}$ ) or the duration of the first phase. This is also true for fibrinogen availability and for fibrinogen concentration at low haematocrits. At high haematocrits $m_{1}$ increases with fibrinogen concentration. The rate of fall of rouleaux during phase 2 ( $m_{2}$ ) and ESR $_{60}$ both decrease exponentially with haematocrit and increase linearly with fibrinogen concentration. While $m_{2}$ is more closely correlated to fibrinogen availability than to fibrinogen concentration or to haematocrit, this is not the case for ESR $_{60}$ . Thus haematocrit, fibrinogen concentration and fibrinogen availability are more important to the velocity of sedimentation in the second phase than to the sedimenting velocity during phase 1 or to the duration of phase 1.
Computer modeling of fluid dynamics related to a myocardial bridge in a coronary artery
Authors: Liu Hao , Yamaguchi Takami
Published: November 2024

Fluid mechanics associated with blood flows induced by the so‐called myocardial bridge (MB) has been studied systematically using a computational fluid dynamic modeling of the Newtonian, incompressible, two‐dimensional, unsteady flow in a channel with a time‐dependently flushing in/out indentation. During each cycle, a train of vortex wave flow was observed downstream of the phasic stenosis and both upper and lower walls suffer severely from consistently high, oscillating wall shear stresses (WSS). Extensive studies were conducted on the influence of the Reynolds number, the geometry and the Strouhal number of the MB movement on the nature of the vortex flow and the time‐dependent wall shear stress distribution.

Special attention was drawn to the relationship between the vortex wave and the pressure distribution. It was found that the pressure gradient changed markedly during one cycle, which was apparently dominated by the dynamics of the indentation. A steep, adverse pressure gradient was observed when the indentation was flushing out, which corresponded to the existence of the most developing vortices. It implies the possibility that the MB in a coronary artery can produce an extremely low pressure region immediately downstream of the phasic stenosis, where elastic choking or collapse of the coronary artery might occur.
Modulation of the mechanical properties of tissue engineered cartilage
Authors: Martin I. , Obradovic B. , Treppo S. , Grodzinsky A.J. , Langer R. , Freed L.E. , Vunjak‐Novakovic G.
Published: November 2024

Cartilaginous constructs have been grown in vitro using chondrocytes, biodegradable polymer scaffolds, and tissue culture bioreactors. In the present work, we studied how the composition and mechanical properties of engineered cartilage can be modulated by the conditions and duration of in vitro cultivation, using three different environments: static flasks, mixed flasks, and rotating vessels. After 4–6 weeks, static culture yielded small and fragile constructs, while turbulent flow in mixed flasks induced the formation of an outer fibrous capsule; both environments resulted in constructs with poor mechanical properties. The constructs that were cultured freely suspended in a dynamic laminar flow field in rotating vessels had the highest fractions of glycosaminoglycans and collagen (respectively 75% and 39% of levels measured in native cartilage), and the best mechanical properties (equilibrium modulus, hydraulic permeability, dynamic stiffness, and streaming potential were all about 20% of values measured in native cartilage). Chondrocytes in cartilaginous constructs remained metabolically active and phenotypically stable over prolonged cultivation in rotating bioreactors. The wet weight fraction of glycosaminoglycans and equilibrium modulus of 7 month constructs reached or exceeded the corresponding values measured from freshly explanted native cartilage. Taken together, these findings suggest that functional equivalents of native cartilage can be engineered by optimizing the hydrodynamic conditions in tissue culture bioreactors and the duration of tissue cultivation.
The influence of mechanical loading on isolated chondrocytes seeded in agarose constructs
Authors: Lee David A. , Noguchi Takashi , Frean Stephen P. , Lees Peter , Bader Dan L.
Published: November 2024

Articular cartilage is subjected to dynamic compressive loading during normal activity which influences chondrocyte metabolism through various mechanotransduction pathways. A well characterised and reproducible model system, involving chondrocytes embedded in agarose gel, has been used to investigate the effects of mechanical compression on chondrocytes, isolated from full depth cartilage or separately from the superficial and deep zone tissue. The role of nitric oxide as a mediator of mechanical‐induced effects has also been studied.

Chondrocytes were isolated, separately, from full depth, superficial and deep zone cartilage and seeded in 3% agarose constructs. Dynamic compressive strain was applied to the constructs using a range of frequencies (0.3, 1 and 3 Hz). Glycosaminoglycan synthesis, cell proliferation and nitrite production were assessed. In further experiments, constructs were compressed in the presence of 1 mM L‐NAME or 10 μM dexamethasone.

Glycosaminoglycan synthesis by full depth chondrocytes was affected by compressive strain in a frequency dependent manner. Dynamic strain at all frequencies induced an increase in [ $^{3}$ H]‐thymidine incorporation. Glycosaminoglycan synthesis by deep zone cells was affected by the strain regimes in a similar fashion to full depth cells, while superficial cells exhibited a similar proliferative response to full depth cells. Dynamic compression inhibited nitrite production, the effect being reversed by L‐NAME. Compression induced stimulation of [ $^{3}$ H]‐TdR incorporation was reversed by L‐NAME.

These studies demonstrate that glycosaminoglycan synthesis and proliferation are influenced by the dynamic strain regimes in a distinct manner. Indeed the data suggest that these processes occur in different chondrocyte sub‐populations. It may be speculated that nitric oxide acts as a mediator of mechanotransduction processes affecting proliferation primarily in the superficial cell sub‐population.
The deformation behavior and viscoelastic properties of chondrocytes in articular cartilage
Authors: Guilak Farshid
Published: November 2024

Chondrocytes in articular cartilage utilize mechanical signals in conjunction with other environmental factors to regulate their metabolic activity. However, the sequence of biomechanical and biochemical events involved in the process of mechanical signal transduction has not been fully deciphered. A fundamental step in determining the role of various factors in regulating chondrocyte activity is to characterize accurately the biophysical environment within the tissue under physiological conditions of mechanical loading. Microscopic imaging studies have revealed that chondrocytes as well as their nuclei undergo shape and volume changes in a coordinated manner with deformation of the tissue matrix. Through micromechanical experiments, it has been shown that the chondrocyte behaves as a viscoelastic solid material with a mechanical stiffness that is several orders of magnitude lower than that of the cartilage extracellular matrix. These properties seem to be due to the structure of the chondrocyte cytoskeleton, and in part, the viscoelastic properties of the cell nucleus. The mechanical properties of the pericellular matrix that immediately surrounds the chondrocyte significantly differ from those of the chondrocyte and the extracellular matrix, suggesting that the pericellular matrix plays an important role in defining the mechanical environment of the chondrocyte. These experimentally measured values for chondrocyte and cartilage mechanical properties have been used in combination with theoretical constitutive modeling of the chondrocyte within articular cartilage to predict the non‐uniform and time‐varying stress‐strain and fluid flow environment of the cell. The ultimate goal of these studies has been to elucidate the sequence of biomechanical and biochemical events through which mechanical stress influences chondrocyte activity in both health and in disease.
Secretory response of endothelin‐1 in cultured human glomerular microvascular endothelial cells to shear stress
Authors: Wang Guixue , Cai Shaoxi , Deng Xiaoyan , Ouyang Keqing , Xie Guoming , Guidoin Robert
Published: November 2024

The shear‐induced secretory response of endothelin‐1 (ET‐1) by human microvascular endothelial cells was studied using paired human glomerular microvascular endothelial cell (HGMEC) cultured monolayers exposed to steady‐state laminar shear stress for up to 10 hours. The first cell monolayer was subjected to a shear stress of 0.65 N m−2 and the second, 1.3 N m−2. ET‐1 secretion was determined by radioimmunoassay. Over 10 hours of shear, the total cumulative secretion of ET‐1 was 237.4 pg/cm2 for the monolayer exposed to 1.3 N m−2 and 143.6 pg/cm2 for the monolayer exposed to 0.65 N m−2. The average ET‐1 secretion rate was 20.90±2.15 and 12.45±1.05 pg/cm2.h at 0.65 N m−2 and 1.3 N m−2, respectively. The results showed that ET‐1 secretion varied with the time of shear in a nonlinear fashion. Although the level of shear stress affected the absolute value of ET‐1 cumulative secretion and secretion rate, the major secretion period for both monolayers occurred between 2.0 and 8.0 hours, with the peak secretion rate occurring at approximately 5 hours. Thus, the response of cultured human microvascular endothelial cells to shear stress differed from that of large vessel endothelial cell cultures in terms of ET‐1 secretion. In addition to the level of shear stress, the time of shear was also an important determinant of ET‐1 secretion. Consequently, the heterogeneity of vascular endothelial cells and the time of shear should both be considered in future research on the secretion of vascular endothelial cell cultures.