bluuebunny/crossref_metadata_2025 huggingface dataset:
CD49a Targeting Enhances NK Cell Function and Antitumor Immunity
Authors: Zhang Yu , Li Yangyang , Zhang Zhengfeng , Zheng Xiaodong , Peng Hui , Tian Zhigang , Sun Rui , Sun Haoyu
Published: November 2024

Approximately 70% of patients receiving immune checkpoint blockade therapies develop treatment resistance. Thus, there is a need for the identification of additional immunotherapeutic targets. CD49a is a membrane protein expressed on NK cells and T cells. In this study, we found that CD49a was highly expressed on the surface of tumor-infiltrating NK cells in various mouse tumor models and that CD49a+ tumor-infiltrating NK cells were more exhausted than CD49a− tumor-infiltrating NK cells. Furthermore, CD49a or NK-specific CD49a deficiency slowed tumor growth and prolonged survival in several mouse tumor models, primarily through the essential role played by NK cells in antitumor activities. Blockade of CD49a using an mAb suppressed tumor development in mice, and combination treatment with anti–PD-L1 further enhanced antitumor efficacy. Our research reveals CD49a on NK cells as an immunotherapeutic target and highlights the potential clinical applications of CD49a-targeted therapies.
Human Amniotic Membrane Graft in the Management of Peripheral Hypertrophic Subepithelial Corneal Degeneration: A Case Report
Authors: Rosetta Pietro , Battaglia Bruno , Watarkar Sakshi , Feo Alessandro
Published: November 2024

Introduction: In this report, we describe the case of peripheral hypertrophic subepithelial corneal degeneration (PHSCD), managed with surgical excision and a human amniotic membrane (hAM) graft. Case Presentation: A 45-year-old female Caucasian patient presented with decreased vision, itching, and burning in both eyes, and a presence of pseudopterygium in the right eye, causing visual decline. Routine ocular exams and anterior segment OCT led to the diagnosis of PHSCD, after a careful differential diagnosis with other similar clinical occurrences. Subsequently, the patient was successfully managed with surgical intervention and an amniotic membrane graft placement. Conclusion: PHSCD is a rare disease, which in advanced cases can be successfully managed with hAM graft. No recurrence of the lesions was observed at 1-year follow-up in our patient.
Exploring the Landscape of Perioperative Immediate Hypersensitivity: A Comprehensive 6-Year Monocentric Observational Analysis on Epidemiology and Risk Factors
Authors: Moreau Arthur , Chérifa Ményssa , Roland Eric , Mc Gee Kathleen , Plaud Benoît , Gouel-Cheron Aurélie , Blet Alice
Published: November 2024

Introduction: Perioperative immediate hypersensitivity (POH) is a rare complication estimated at 1/10,000 anaesthesia. The objective of our study was to investigate the risk factors of POH over a 6-year period in a French teaching hospital. Materials and Methods: A single-centre retrospective descriptive epidemiological study of patients treated in the operating room from January 2016 to December 2021 with and without POH. Results: 111 POH were identified out of 47,585 surgeries, mainly women (71%) with a history of asthma (16% vs. 6%, p < 0.001) undergoing plastic surgery (49% vs. 32%, p < 0.001). POH patients were more likely to receive neuromuscular blocking agents and antibiotics (respectively, 88% vs. 59%, p < 0.001 and 59% vs. 24%, p < 0.001). 92% of patients underwent intraoperative sampling, only 31% benefited from an allergy consultation. 14% had positive skin test (ST). The culprit agent were neuromuscular blocking agents (47% of which 57% rocuronium, 29% suxamethonium, and 14% atracurium), antibiotics (33%, of which 80% cefazolin and 20% cefoxitin), and gelatin (7%). Conclusion: Our study reported a POH incidence of 23/10,000 anaesthesia, with identified allergens aligning with existing literature. These findings underscore the critical need for enhanced patient follow-up to monitor potential hypersensitivity and mitigate future risks.
A Unique Case of Bilateral Testicular Tumours: Nonseminomatous Germ Cell Tumour and Contralateral Spermatocytic Tumour 27 Years Apart
Authors: Dieckmann Klaus-Peter , Harms Alexander , Belge Gazanfer , Wülfing Christian
Published: November 2024

Introduction: Bilateral testicular tumours occur in 3–5% of all cases with testicular neoplasms. In the majority of cases, histology of the two new growths is identical. The time interval between the two neoplastic events rarely exceeds 10 years. Case Presentation: A 29-year-old man of Caucasian descent underwent right-sided orchiectomy for a nonseminomatous germ cell tumour (GCT). Postoperatively, he received adjuvant chemotherapy with 2 cycles of a cisplatin based regimen for clinical stage 1 disease. Twenty-seven years later when aged 56 years, he developed a lump in the left testis. Serum tumour markers including microRNA-371a-3p were within normal limits. Orchiectomy was performed. Histology revealed a spermatocytic tumour with positive stainings of SALL4, NUT, and CD117. No germ cell neoplasia in situ (GCNis) was detected in the tumour-surrounding tissue. Conclusion: Histogenetically, testicular GCTs are thought to derive from the precursor GCNis, while spermatocytic tumours directly derive from adult spermatogonia. This case is exceptional, firstly because of the very long interval of 27 years between the two neoplastic events, and secondly because of the unprecedented occurrence of two testicular neoplasms with different pathogenetic origins in 1 individual patient.
Educational management in a digital age: boss phubbing and teacher motivation
Authors: Erdem Mukadder , Kaya Esra
Published: November 2024

The study aims to assess the level of phubbing behavior an antisocial common mobile phone using behavior of school principals and how it affects the motivation of the teachers working at Anatolian High Schools and Vocational High Schools. This relational screening modelled study was conducted in these schools in the 2nd term in 2022 to 2023 school year. For data collection purposes, Boss Phubbing Scale and Multidimensional Work Motivation Scale were used and 268 answers were collected from the whole population. The data was analyzed through descriptive statistics, exploratory factor analysis (EFA), Cronbach’s alpha reliability analysis, one-way analysis of variance (ANOVA), unpaired t test, Pearson correlation analysis and regression analysis. The data derived from these analyses indicates that while school principals phub teachers at a low level and their boss phubbing scores differentiate in accordance with the work experience of teachers; teachers’ motivation is high and there is a significant and positive relationship between boss phubbing of school principals and two factors of Multidimensional Work Motivation Scale, which were extrinsic motivation and amotivation. It may be suggested that school principals should alter their boss phubbing behavior or modify it to make the best of it.
Development and validation of Indonesian youth career identity scale: the Rasch analysis
Authors: Agungbudiprabowo Agungbudiprabowo , Purwanta Edi , Wangid Muhammad Nur
Published: November 2024

Career identity is one of the most important psychosocial developmental tasks for adolescents. The development of career identity in adolescence will prevent humans from experiencing identity confusion which will have an impact on further developmental tasks. This research answers the need for this measurement tool by developing and validating a career identity measurement tool called the Indonesian youth career identity scale (IYCIS). This instrument consists of 55 items in two aspects: career exploration and commitment. This study uses Rasch analysis to test the validity of the IYCIS construct. The construct validity test involved 200 high school students in Yogyakarta, Indonesia. Data analysis using Winstep software provides information about the quality of respondents and instruments, items that are easy and difficult for respondents to agree on, items that are made to order, and unidimensional. The results of applying the Rasch analysis show that IYCIS is good, precise, and has an item fit with the model. IYCIS is a reliable and valid measurement tool for accurately measuring the level of student career identity. This study discusses the implications and recommendations for further research on the implementation of guidance and counseling that contains career identity as a follow-up to IYCIS performance.
The influence of perceive teacher support on high school students’ learning engagement in China
Authors: Yang Liu , Lian Lim Hooi
Published: November 2024

This study explores the influence of perceived teacher support on learning engagement and the mediating role played by psychological capital of senior high school students. There were 572 Chinese senior high school students from Inner Mongolia Autonomous Region in China completed a ranger of self-report questionnaires. The results of this study showed that perceived teacher support was significantly and positively related to learning engagement of senior high school students, and positively correlated with their psychological capital which consists of four dimensions: hope, self-efficacy, optimism, and resilience. The psychological capital was significantly and positively associated with learning engagement among senior high school students and mediated the relationships between perceived teacher support and learning engagement.
Relationship of TPACK, motivation, self-regulation, and learning performance on preservice primary school teachers
Authors: Thohir M. Anas , Yanti Fitri April , Handayani Rif’ati Dina , Halim Lilia
Published: November 2024

Technological development could enable pre-service teachers to adopt web design with strong pedagogy, however adaptation requires still unclear an explicit exploration of the factors. This study aimed to identify the effect of technological pedagogical content knowledge (TPACK) on motivation, self-regulation, and learning achievement. It surveyed 406 pre-service teachers from 12 higher education institutions in Indonesia. Data validity and reliability were checked using an exploratory factor, confirmatory, and part analyses. The partial least squares structural equation modelling (PLS-SEM) results showed that TPACK has the most significant role in learning motivation. The result shows that technology integration knowledge also significantly affects self-regulated learning (SRL). In addition, pre-service teachers’ TPACK supports their learning motivation to use the web, as well as their academic achievement. Moreover, most students’ achievements were constructed by TPACK, learning motivation, and self-regulation. This study implies that the instructor should clarify the project mission and the inquiry system activities in the educational technology course.
Effects of professional learning communities on job satisfaction of female teachers in Vietnam
Authors: Ly Nguyen Thanh , Hong Nguyen Van
Published: November 2024

This study focuses on this topic to better understand how professional learning communities (PLCs) affect the work satisfaction of female primary school teachers in Vietnam. By utilizing the Statistical Package for the Social Sciences (SPSS 26) to evaluate our sample of 675 female primary school teachers, we were able to provide insight into the efficacy of PLCs in enhancing work satisfaction levels. The findings show that, among this population, participation in PLCs is significantly correlated with higher job satisfaction. In which, the collective learning and application (LA) element is followed by the shared and supportive leadership (SS), supportive conditions—relationships (SR), supportive conditions—structures (CS), and shared personal practice (PP) elements, shared values and vision (VV) has the most minor influence. Using PLCs as a workable solution to improve female educators’ working conditions and job satisfaction emphasizes the possible advantages for educational practice and policy.
Evaluation of ChatGPT research in STEAM education
Authors: Prahani Binar Kurnia , Nisa’ Khoirun , Suliyanah Suliyanah , Deta Utama Alan
Published: November 2024

Research focus of reviews trends and research on implementing ChatGPT in science, technology, engineering, arts, and math (STEAM) learning. It emphasizes the importance of deep learning and 21st-century skills in education, highlighting the limitations of ChatGPT in accuracy and credibility. The authors analyzed 204 STEAM education documents, revealing that 65% focused on technology education and less than 3% on art and mathematics education. The articles written in technology scope are the most widely circulated. The most productive region is the United States, which has three productive authors. The most productive authors are Ray (India) and Wang (Macao), who have the highest h-index. The United States and United Kingdom are the most productive affiliations. Many types of research on ChatGPT in STEAM education include a survey with several participants of different education levels. Social science is the most popular subject area. The Journal Nature is the primary source for this research. Several research highlighted artificial intelligence, ChatGPT, and human keywords. This study highlights the potential of ChatGPT in STEAM, suggesting further research on student behavior, learning designs, and credibility concerns. It suggests collaboration with Google Scholar or Web of Science data for in-depth analysis.
Education and smart technologies: towards a new pedagogical paradigm
Authors: Dehbi Amine , Bakhouyi Abdellah , Khaddar Al Mahdi , Talea Mohamed
Published: November 2024

Smart education, a new field of technology related to education, has emerged as a unique response to current educational challenges. This is becoming increasingly important for academic progress and aligns with the transformative impact of technology. This study addresses the transformative impact of smart technologies on education, focusing on the integration of the internet of things, big data, and artificial intelligence. Through a bibliometric and content analysis based on Scopus and Web of Science databases, we identify the most active researchers, leading universities, and the countries that contribute most significantly to the field of smart education. The findings reveal a significant increase in related publications, highlighting the growing importance of these technologies in enhancing teaching and learning experiences. The study shows the advantages and challenges of adopting such technologies, providing insights into their practical applications and the future direction of educational innovations. Integrating smart technologies in education is crucial for improving quality of life and academic outcomes, necessitating further research and development to fully realize their potential. This research contributes to the understanding of technological impacts on education and supports the development of strategies for their effective implementation.
Student engagement as a mediator between online classroom management and learning outcomes in Beijing universities
Authors: Fei Li Yi , Radzi Norfariza Mohd , Hoque Kazi Enamul
Published: November 2024

Online classroom management is considered essential for promoting student learning outcomes and engagement. This study examines the relationship between online classroom management and student learning outcomes, with student engagement as a mediator. A cross-sectional survey method was employed to collect data via questionnaires distributed through Google Forms. Respondents were selected using multi-stage cluster sampling from six universities in Beijing, China. A total of 400 valid questionnaires were analyzed quantitatively using SPSS to address the research questions. The findings indicate that online classroom management positively correlates with student engagement and learning outcomes. Moreover, student engagement significantly mediates the relationship between online classroom management and student learning outcomes. The study validates the model that online classroom management, mediated by student engagement, positively influences university students’ learning outcomes, thus supporting the research hypotheses based on the relationships among the variables. This study contributes to the integration of theory and enhances the understanding of the relationship between online classroom management and student learning outcomes. Additionally, it offers insights for policymakers and practitioners on how to support online classroom management and improve student learning outcomes.
EMPOERING MSMEs : Enhancing Resource Access, Croudfunding and Incubation Initiatives
Authors: Velenzuela Victoria P , Evardone Carlo Jay A , Vergara Kimberly Christie S , Vergara Raymond Allan G
Published: November 2024

This chapter investigates mindfulness's role in building resilience toward survivability, sustainability, and better governance of micro, small, and medium enterprises through extensive literature review and in-depth analysis of Barangay Nagbalon experience, this examines how the role of mindfulness in building resilience, survivability, sustainability, and better governance in Micro, Small, and Medium Enterprises (MSMEs), mindfulness practices have been implemented in Micro, Small, and Medium Enterprises (MSMEs) to promote resilience, sustainability, and better governance, challenges in incorporating mindfulness into different organizational cultures analyzed, this chapter highlights the role of stakeholders in Barangay Nagbalon achieving resilient, sustainable, and better governance of MSMEs in the context of innovation and incubation initiatives, the significant relationship between mindfulness practices and SAMAKANA enterprise success in times of crisis, and the identified implications of harnessing mindfulness in building resilience, sustainability, and better governance in Municipality of Marilao. This explanatory chapter was also based on the secondary data and literature review and aspires to offer deeper insights for entrepreneurs, innovators, educators, business owners, and other professionals into the role of mindfulness in building resilience, survivability, sustainability, and better governance in Municipality of Marilao.
Scholarly and Empirical Considerations on Expanding Access for Non-Governmental Organisations Before the European Court of Human Rights
Authors: Erken Elif
Published: November 2024

Non-governmental organisations (ngo s) have long been considered important actors within the European Convention on Human Rights (echr) system. Yet, their influence as litigants remains limited when a case with a specific individual, rather than a general situation, is put before the European Court of Human Rights (ECtHR or Court). This article evaluates the Court’s standing requirements and in doing so, brings together various perspectives on ngo s and the strategies they pursue. By drawing upon interviews with Court officials, ngo representatives, including those with experience litigating under the collective complaints procedure of the European Social Charter (esc), and experts who sit in the esc Committee, it includes a stakeholder perspective on the need to further allow ngo s to engage strategically before the Court and whether inspiration can be derived from the esc system, with specific focus on formalising greater access for ngo s.
Normative Agency and Cross-Cultural Human Rights in East Asia
Authors: Corrigan Daniel P. , Cokelet Bradford
Published: November 2024

According to James Griffin (2008) human rights should be grounded in an account of human dignity, based on “normative agency” – the human capacity to choose and pursue a conception of a worthwhile life. In this paper we take up Griffin’s insight that key legitimate human rights are designed to respect and protect this basic capacity, but reject his assumption that normative agency should always and everywhere be understood in a Western way. We argue that “normative agency” is an indeterminate concept that can be differently understood in different cultural contexts and that thinking about human rights in East Asia should be guided by a Griffin-style approach coupled with an account of normative agency with East Asian characteristics. In developing this idea, we contrast our account with recent, moralized conceptions of Confucian dignity and respond to Griffin’s tacit worries about how to concretely implement views like ours in institutional practice.
A fiber matrix model for interstitial fluid flow and permeability in ligaments and tendons\thanks Partial results were presented in the 1993 Summer Bioengineering Conference, Breckenridge, CO, June 17, 1993, and in the 40th Annual Meeting of the Orthopaedic Research Society, New Orleans, LA, February 23, 1994.
Authors: Chen Chih‐Tung , Malkus David S. , Vanderby Ray
Published: November 2024

Collagen fibrils in ligaments and tendons are highly organized into parallel arrays which influence interstitial fluid transport. Finite element (FE) models were developed analogous to the fibrillar arrays in ligaments and tendons to investigate interstitial fluid flow and tissue permeability as a function of interfibrillar spacing and fluid properties. Collagen fibrils were assumed to be a periodic square array of impermeable cylinders. A two‐dimensional FE model was used to study transverse fluid flow and a three‐dimensional model was used to study flow parallel to the collagen fibrils. Parametric FE analysis provided data to formulate empirical expressions for permeability ( $\kappa$ ) as a function of porosity ( $\phi$ ). Results show that longitudinal permeability ( $\kappa=1.1\cdot 10^{-15} \phi^{2.5}[1-\phi]^{-0.333}$ ) can be up to 50 times higher than transverse permeability ( $\kappa=1.2\cdot 10^{-15} \phi^{0.5}[\phi-\phi_{\min}]^{2.5}$ ) in a compact array. Maximum fluid shear stresses occur at the narrowest zones of adjacent fibrils (1.21 Pa or 12.1 dyn/cm $^{2}$ at 10 $\mu$ m/s of average transverse influx). If interstitial fluid is highly non‐Newtonian, the permeability should be considered as flow (shear)‐dependent. The computational results suggest that tissue permeability in ligaments and tendons is highly anisotropic, porosity‐dependent, and can be estimated by analytic expressions.
Use of polyester leukocyte elimination filters in blood filterability research
Authors: Lindmark Krister , Engström K. Gunnar
Published: November 2024

We tested a new routine to eliminate leukocytes for blood rheology measurements using commercial leukocyte absorbing filters (here PALL RC400). These filters were punched out and fitted in smaller chambers through which blood was filtered under controlled suction pressure ( $<30$ mm Hg). This technique resulted in a very effective leukocyte elimination to 0.0022% but also a platelet reduction to 0.2%. The process causes a small but significant hemolysis with free hemoglobin, of the order of 0.06% of the filtered erythrocytes. A small fraction of the erythrocytes were retained in the filter, versus plasma, to reduce the hematocrit on the order of 1.4%. The leukocyte filtration did not cause any detectable functional trauma to the erythrocytes, measured as micro‐pore filterability of normal and glutaraldehyde (GA) hardened erythrocytes. However, when 10% of the erythrocytes were hardened with GA, which caused an increase in pore clogging slope ( $p<0.05$ ), the additional passage through the leukocyte elimination filter removed this measured change in clogging. This observation suggests that the leukocyte elimination filter may selectively remove, not only leukocytes and platelets, but also hardened erythrocytes. Reticulocyte counting did not reveal any selective removal of young erythrocytes. In general, we find the presented method reproducible, efficient and easy for eliminating leukocytes for blood rheology research although the risk of removing undeformable erythrocytes must be considered.
The osmotic pressure of chondroitin sulphate solutions: Experimental measurements and theoretical analysis
Authors: Ehrlich S. , Wolff N. , Schneiderman R. , Maroudas A. , Parker K.H. , Winlove C.P.
Published: November 2024

We used equilibrium dialysis to measure the osmotic pressure of chondroitin sulphate (CS) solutions as a function of their concentration and fixed charge density (FCD) and the ionic strength and composition of the solution. Osmotic pressure varied nonlinearly with the concentration of chondroitin sulphate and in 0.15 M NaCl at FCDs typical of uncompressed cartilage (approximately 0.4 mmol/g extrafibrillar H $_{2}$ O) was $\sim$ 3 atmospheres. Osmotic pressure fell by 60% as solution ionic strength increased up to about 1 M, but remained relatively constant at higher ionic strengths. The ratio of Ca $^{2+}$ to Na $^{+}$ in the medium was a minor determinant of osmotic pressure. The data are compared with a theoretical model of the electrostatic contribution to osmotic pressure calculated from the Poisson–Boltzmann equation using a rod‐in‐cell model for CS. The effective radius of the polyelectrolyte rod is taken as a free parameter. The model qualitatively reproduces the non‐linear concentration dependence, but underestimates the osmotic pressure by an amount that is independent of ionic strength. This difference, presumably arising from oncotic and entropic effects, is approximately $1/3$ of the total osmotic pressure at physiological polymer concentrations and ionic strength.
Linear viscoelastic model of a maturing gelatin solution
Authors: Braidot Ariel A.A. , Deiber Julio A.
Published: November 2024

The linear viscoelastic model proposed in this work considers the viscoelastic nature of maturing gelatin solutions through a relaxation modulus that depends on temperature and maturation. This modulus is defined in the conceptual contexts of the classical rubber elasticity theory and the rheometric gel theory. An analysis of the relationship between the equilibrium elastic modulus and the percolation variable around the gel point is also included yielding a percolation exponent close to 1.7 as expected from previous theoretical predictions. Additionally, a simple kinetic model is proposed to follow the microstructural changes obtained as a consequence of the generation of junction zones, the number of which vary with time during the dynamic rheometric tests used in this work. Thus, the storage and loss moduli are measured at different temperatures and frequencies, during the period of gelatin maturation. The theoretical aspects of the rheological model are presented emphasizing the quantitative changes of rheological parameters with the maturation.
Flow‐dependent concentration polarization of plasma proteins at the luminal surface of a cultured endothelial cell monolayer
Authors: Naiki Takeru , Sugiyama Hironobu , Tashiro Rumi , Karino Takeshi
Published: November 2024

Flow‐dependent concentration or depletion of atherogenic low density lipoproteins which has been theoretically predicted to occur at a blood/endothelium boundary may play an important role in the genesis, progression, and regression of atherosclerosis in man and intimal hyperplasia in vascular grafts implanted in the arterial system in man and experimental animals. Hence to explore such a possibility, we have studied the effect of a steady shear flow on concentration polarization of plasma proteins and lipoproteins at the luminal surface of a cultured bovine aortic endothelial cell (BAEC) monolayer which served as a model of the vessel wall of an artery or an implanted vascular graft. The study was carried out by circulating a cell culture medium containing fetal calf serum or bovine plasma lipoproteins in steady flow through a parallel‐plate flow cell in which a cultured BAEC monolayer was installed, over the physiologic ranges of wall shear rate and water filtration velocity at the BAEC monolayer. The water (cell culture medium) filtration velocity at the BAEC monolayer was determined to provide a measure of the change in concentration of plasma protein particles at the luminal surface of the BAEC monolayer. It was found that for perfusates containing plasma proteins and/or lipoproteins, water filtration velocity varied as a function of flow rate, being lowest in the absence of flow. Water filtration velocity increased or decreased as flow rate increased or decreased from an arbitrarily set non‐zero value, indicating that surface concentration of protein particles varied as a direct function of flow rate, and the process was reversible. It was also found that at particle concentrations equivalent to those found in a culture medium containing serum at 20% by volume, plasma lipoproteins which were much smaller in number and lower in concentration but larger in size than albumin, showed almost the same effect as observed with serum which contained both lipoproteins and albumin, indicating that the substance responsible for this phenomenon is not albumin but lipoprotein whose diffusivity is much smaller than that of albumin. The results strongly support our hypothesis that flow‐dependent concentration polarization of lipoproteins occurs at a blood endothelium boundary, and this in turn promote the localization of various vascular diseases which develop in our arterial system.
Mucus liquid crystallinity: is function related to microstructural domain size?
Authors: Viney C.
Published: November 2024

The size of liquid crystalline domains formed in partially dried giraffe saliva is found to be an order of magnitude greater than that previously documented for slug pedal mucus. A correlation between (a) intrinsic liquid crystalline domain size and (b) the scale of surface topography over which the mucus is required to provide lubrication is postulated. The scale of mucus microstructure can be related, via a simple model, to two significant material constants: the elastic constant $K$ for distortion of molecular alignment in the liquid crystalline state, and the anchoring energy $I$ at the liquid crystal/substrate interface. In turn, the quantity $K$ is expected to depend on fundamental molecular characteristics of the constituent mucin, such as molecular weight and degree of glycosylation. The possibility that observations of mucus microstructure might serve as a diagnostic tool for mucus defects at the molecular level is suggested.
Dielectric approach to the investigation of erythrocyte aggregation: I. Experimental basis of the method
Authors: Pribush A. , Meiselman H.J. , Meyerstein D. , Meyerstein N.
Published: November 2024

A method based on dielectric properties of dispersed systems was developed to investigate red blood cell (RBC) aggregation in blood and RBC suspensions. Measurements of capacitance and resistance were made in a rectangular channel at low (0.2 MHz) and high (14 MHz) frequencies relative to the mid‐point of the β‐dispersion range. Compared to capacitance, minimal post‐shearing changes of resistance were observed; capacitance changes at 0.2 MHz were two orders of magnitude larger than those at 14 MHz and hence subsequent measurements were carried out at the lower frequency. It is shown that post‐shearing changes in the capacitance are affected by the recovery of RBC shape and relaxation processes at the electrode‐suspension interface. However, the dominant factor contributing to time‐dependent changes in the capacitance is the dynamic process of RBC aggregation. It is experimentally shown that the time record of the capacitance at 0.2 MHz quantitatively reflects the aggregation process in RBC‐plasma suspensions with hematocrit up to 0.56 (v/v) and in suspensions of RBCs in artificial aggregating media. It is concluded that a dielectric approach to the study of RBC aggregation in whole blood offers great potential for basic studies and for diagnostic use.
The role of chondrocyte–matrix interactions in maintaining and repairing articular cartilage
Authors: Martin J.A. , Buckwalter J.A.
Published: November 2024

Throughout life chondrocytes maintain the articular cartilage matrix by replacing degraded macromolecules and respond to focal cartilage injury or degeneration by increasing local synthesis activity. These observations suggest that mechanisms exist within articular cartilage that stimulate chondrocyte anabolic activity in response to matrix degradation or damage. An important cartilage anabolic factor, insulin‐like growth factor I (IGF‐I), appears to have a role in stimulating chondrocyte anabolic activity. Although IGF‐I is ubiquitous, its bioavailability is controlled by a class of secreted proteins, IGF binding proteins (IGFPBs). Of the six known IGFPBs, IGFBP‐3 is the most abundant in human articular cartilage. We recently found that with increasing age, articular chondrocytes increase their expression of IGFBP‐3. This observation led us to investigate the potential role of IGFBP‐3 in chondrocyte–matrix interactions. Using immunofluorescent staining and confocal microscopy we found that IGFBP‐3 accumulates with increasing age in the chondrocyte territorial matrix where it co‐localizes with fibronectin, but not with tenascin‐C or type VI collagen. Using purified proteins we demonstrated that IGFBP‐3 binds to fibronectin in a dose dependent manner, but not to tenascin‐C. In vitro studies showed that IGFBP‐3 alone inhibited chondrocyte synthetic activity while intact fibronectin alone significantly stimulated activity. When fibronectin and IGFBP‐3 were combined we found that the inhibitory activity of low concentrations of IGFPB‐3 was enhanced. These observations indicate that in mature articular cartilage IGF‐I is stored in the chondrocyte territorial matrix through binding to a complex of IGFPB‐3 and intact fibronectin. Storage of IGF‐I of the territorial matrix may help maintain a relatively constant level of available IGF‐I and the local increase in matrix synthesis following matrix damage may result from release of IGF‐I. This mechanism may have an important role in maintaining and repairing articular cartilage and failure of this mechanism may lead to progressive articular cartilage degeneration.
The role of 3D‐microscopy in the study of chondrocyte–matrix interaction (alginate bead or sponge, rat femoral head cap, human osteoarthritic cartilage) and pharmacological application
Authors: Dumas D. , Gigant C. , Presle N. , Cipolletta C. , Miralles G. , Payan E. , Jouzeau J.Y. , Mainard D. , Terlain B. , Netter P. , Stoltz J.F.
Published: November 2024

The potentialities of a new non‐invasive optical scanning microscopy technique were evaluated through 3D analysis of chondrocyte–matrix interactions. Five different 2D or 3D culture systems were used: (1) MonoLayer (ML) of human chondrosarcoma cell line; (2) rat or human chondrocytes encapsulated in Alginate Bead (AB); (3) human chondrocytes encapsulated in Alginate Sponge (AS); (4) Rat Femoral Head Cap (RFHC); (5) slices of knee human Osteoarthritic Cartilage (HOAC). Chondrocytes ML, AB, RFHC were incubated for 24 h in vitro in the presence of recombinant human interleukin1‐β (rhIL1‐β) and the effects on cytoskeleton organisation (F‐actin filament), Focal Adhesion Kinase (FAK) expression (tyrosine kinase), collagenase B expression (metalloprotease) were studied. Furthermore, the production of intracellular IL1‐β by LPS‐ or rhIL1‐β‐stimulated chondrocytes was shown to be partly suppressed by rhein (active metabolite of diacerhein) in all culture systems. This high resolution light microscopy gave complementary information that could be important for a better understanding of the interaction of chondrocytes with the extracellular matrix in a variety of culture devices.
Comparison of the viscoelastic properties of normal hepatocytes and hepatocellular carcinoma cells under cytoskeletal perturbation
Authors: Wu Ze‐Zhi , Zhang Gang , Long Mian , Wang Hong‐Bin , Song Guan‐Bin , Cai Shao‐Xi
Published: November 2024

The viscoelastic properties of both hepatocytes and hepatocellular carcinoma (HCC) cells were measured by means of a micropipette aspiration technique. Experimental results were analyzed with a three‐element standard linear solid model, in which an elastic element, K1, is in parallel with a Maxwell element composed of another elastic element, K2, in series with a viscous element, μ. Further, we investigated the relevance of viscoelastic properties of these two types of cells to the cytoskeleton structures by treating cells with three cytoskeletal perturbing agents, namely cytochalasin D (CD), colchicine (Col) and vinblastine (VBL). The results showed that the elastic coefficients, but not viscous coefficient of HCC cells (K1=103.6±12.6 N m−2, K2=42.5±10.4 N m−2, μ=4.5±1.9 Pa s, n=30), were significantly higher than the corresponding values for hepatocytes (K1=87.5±12.1 N m−2, K2=33.3±10.3 N m−2, μ=5.9±3.0 Pa s, n=24). Upon treatment with CD, the viscoelastic coefficients of both hepatocytes and HCC cells decreased uniformly, with magnitudes for the decrease in elastic coefficients of HCC cells (K1: 68.7 to 81.7 N m−2, 66.3 to 78.9%; K2: 34.5 to 37.1 N m−2, 81.2 to 87.3%) larger than those for normal hepatocytes (K1: 42.6 to 49.8 N m−2, 48.7 to 56.9%; K2: 17.2 to 20.4 N m−2, 51.7 to 61.3%). There was a smaller decrease in the viscous coefficient of HCC cells (2.0 to 3.4 Pa s, 44.4 to 75.6%) than that for hepatocytes (3.0 to 3.9 Pa s, 50.8 to 66.1%). Upon treatment with Col and VBL, the elastic coefficients of hepatocytes generally increased or tended to increase while those of HCC cells decreased. The differences in either the pattern or the magnitude of the effect of cytoskeletal perturbing agent on the viscoelastic properties between HCC cells and hepatocytes might possibly reflect differences in the state of the cytoskeleton structure and function, or in the cells' sensitivity to perturbing agent treatment between these two types of cells. Changes in the viscoelastic properties of cancer cells might well affect tumor cell invasion and metastasis as well as interactions between tumor cells and their micro‐mechanical environments.
Mechanical degradation of polyacrylamide solutions as a model for flow induced blood damage in artificial organs
Authors: Pohl Manfred , Wendt Max O. , Koch Brigitte , Vlastos George A.
Published: November 2024

Human or animal blood is normally used as a test fluid for the in vitro evaluation of hemolysis by artificial organs. However, blood has some disadvantages (large biological variability and problems with cleaning the devices). For that reason, we searched for a reproducible technical fluid with blood‐like flow characteristics that exhibits similar shear depending destruction. In this study, a direct comparison between erythrocyte damage of bovine blood and shear‐induced degradation of polyacrylamide solution is given. A uniform shear field was applied to the fluids using a shear device with a plate‐plate geometry.

It was shown that similarities exist between erythrocytes disaggregation and breakdown of super molecular structures in polymer solutions, caused by mechanical stress. In both cases steady low shear viscositity was diminished and the elastic component of complex viscosity of blood and polymer solutions has been reduced. There is a correlation between shear‐induced hemolysis of bovine blood and mechanical polymer‐degradation, which depends on the applied shear stresses.
Biomechanical and morphometric properties of the arterial wall referenced to the zero‐stress state in experimental diabetes
Authors: Zhao Jingbo , Lu Xiao , Zhuang Fengyuan , Gregersen Hans
Published: November 2024

Morphometric and passive biomechanical properties were studied in isolated segments of the thoracic and abdominal aorta, left common carotid artery, left femoral artery and the left pulmonary artery in 20 non‐diabetic and 28 streptozotocin (STZ)‐induced diabetic rats. The diabetic and non‐diabetic rats were divided into groups living 1, 4, 8, and 12 weeks after the induction of diabetes (n=7 for each diabetic group) or sham injection (n=5 for each group). The mechanical test was performed as a distension experiment where the proximal end of the arterial segment was connected via a tube to the container used for applying pressures to the segment and the distal end was left free. The vessel diameter and length were obtained from digitized images of the arterial segments at pre‐selected pressures and at no‐load and zero‐stress states. Circumferential and longitudinal stresses (force per area) and strains (deformation) were computed from the length, diameter and pressure data and from the zero‐stress state data. The zero‐stress state was obtained by cutting vessel rings radially causing the rings to open up into a sector. Diabetes was associated with pronounced morphometric changes, e.g., wall thickness. With respect to the biomechanical data, the opening angle increased and reached a plateau in 4 weeks after which it decreased again (p<0.05). The opening angle was smallest in the thoracic aorta and largest in the pulmonary artery. Furthermore, it was found that the circumferential stiffness of the arteries studied increased with the duration of diabetes. In the longitudinal direction significant differences were found 8 weeks after injection of STZ in all arteries except the pulmonary artery. In the 12 weeks group, the femoral artery was stiffest in the circumferential direction whereas the thoracic aorta was stiffest in the longitudinal direction. The accumulated serum glucose level correlated with the arterial wall thickness and elastic modulus (correlation coefficient between 0.56 and 0.81).
High viscosity plasma expanders: Volume restitution fluids for lowering the transfusion trigger
Authors: Tsai Amy G. , Intaglietta Marcos
Published: November 2024

Hemorheological studies lead to the axiom that high plasma viscosity is detrimental and that it is beneficial to lower blood viscosity, a precept embodied in the practice of hemodilution, where improved perfusion is attributed to the lowering of blood viscosity. Hemodilution is limited by the transfusion trigger, hemoglobin content of blood of about 7–8 g/dl, which indicates when further volume replacements must restore oxygen carrying capacity with red blood cells (RBC). However, oxygen consumption and delivery are not compromised upon passing this landmark. The reduced blood viscosity does not transmit adequate pressure to the capillaries, causing functional capillary density (FCD) to decrease, jeopardizing organ function through the inadequate extraction of products of metabolism from the tissue by the capillaries. Studies in hemorrhagic shock show that survival is primarily determined by the maintenance of FCD and secondarily by tissue oxygenation. FCD is maintained as hematocrit is reduced beyond the transfusion trigger by increasing plasma viscosity, which transmits systemic pressure to the capillaries and induces vasodilatation through the increased shear stress dependent release of vasodilators. Consequently the transfusion trigger is also a “viscosity trigger” indicating when blood and plasma viscosity are too low. In this condition increasing plasma viscosity is beneficial and extends the transfusion trigger reducing the use of blood transfusions.
A new view of mechanotransduction and strain amplification in cells with microvilli and cell processes
Authors: Weinbaum Sheldon , Guo Peng , You Lidan
Published: November 2024

In this paper we shall describe new mechanical models for the deformation of the actin filament bundles in kidney microvilli and osteocytic cell processes to see whether these cellular extensions, like the stereocilia on hair cells in the inner ear, can function as mechanotransducers when subject to physiological flow. In the case of kidney microvilli we show that the hydrodynamic drag forces at the microvilli tip are <0.01 pN, but there is a 38‐fold force amplification on the actin filaments at the base of the microvilli due to the resisting moment in its terminal web. This leads to forces that are more than sufficient to deform the terminal web complex of the microvillus where ezrin has been shown to couple the actin cytoskeleton to the Na+/H+ exchanger. In the case of bone cell processes we show that the actin filament bundles have an effective Young's modulus that is 200 times > the measured modulus for the actin gel in the cell body. It is, therefore, unlikely that bone cell processes respond in vivo to fluid shear stress, as proposed in [59]. However, we show that the fluid drag forces on the pericellular matrix which tethers the cell processes to the canalicular wall can produce a 20–100 fold amplification of bone tissue strains in the actin filament bundle of the cell process.
Biomechanical properties of the human umbilical cord
Authors: Pennati Giancarlo
Published: November 2024

The umbilical cord is a complex and fascinating structure that connects the fetus to the placenta and encases the umbilical vessels. The response of its tissues to mechanical loading due to fetal movements and uterine contractions is not well understood. The aim of this study is the evaluation of the mechanical properties of the main components of the human umbilical cord. Fresh umbilical cord specimens were collected from neonates born at term of the gestation and submitted to compliance tests. Furthermore, uniaxial tensile and stress‐relaxation tests were performed on samples of umbilical vein and Wharton's jelly. Both materials exhibited nonlinear stress–strain response with increasing strain, increasing the elastic modulus (Ehigh about 10–20 times Elow) and significant viscoelastic behavior. In addition, anisotropy of the vein was observed. Although the circumferential properties of the vein (mean Ehigh about 2.4 MPa) were similar to those after birth, the longitudinal stiffness of both materials was higher (mean Ehigh over 10 MPa) and comparable to that of the ligaments. These findings suggest a mechanism of protection acting against excessive elongations of the cord, which could cause undue restriction of the umbilical vessel area and interference with the fetal blood circulation.
Red blood cell rheological alterations in a rat model of ischemia‐reperfusion injury
Authors: Kayar E. , Mat F. , Meiselman H.J. , Baskurt O.K.
Published: November 2024

Red blood cell (RBC) deformability and aggregation characteristics were investigated in an experimental model of ischemia‐reperfusion injury. Ischemia was produced in rat hind limb by occluding the femoral artery for 10 minutes, followed by reperfusion. Blood samples were obtained either following the ischemia or 15 minutes after reperfusion. RBC deformability measured by ektacytometry was found to be significantly impaired immediately after the end of ischemic period in the blood samples obtained from femoral vein of the ischemic limb, while there was no significant difference after 15 minutes of reperfusion. In contrast, RBC aggregability was found to be decreased only after the reperfusion period and this alteration was not only limited to the blood returning from the ischemic limb but was also observed in the samples obtained from non‐ischemic, contralateral hind limb, indicating a systemic alteration. RBC electrophoresis studies suggested that the altered aggregability might be related to altered RBC surface properties including increased RBC surface charge density.
A two‐phase model for flow of blood in narrow tubes with increased effective viscosity near the wall
Authors: Sharan Maithili , Popel Aleksander S.
Published: November 2024

A two‐phase model for the flow of blood in narrow tubes is described. The model consists of a central core of suspended erythrocytes and a cell‐free layer surrounding the core. It is assumed that the viscosity in the cell‐free layer differs from that of plasma as a result of additional dissipation of energy near the wall caused by the red blood cell motion near the cell‐free layer. A consistent system of nonlinear equations is solved numerically to estimate: (i) the effective dimensionless viscosity in the cell‐free layer (β), (ii) thickness of the cell‐free layer (1−λ) and (iii) core hematocrit (Hc). We have taken the variation of apparent viscosity (μapp) and tube hematocrit with the tube diameter (D) and the discharge hematocrit (HD) from in vitro experimental studies [16]. The thickness of the cell‐free layer computed from the model is found to be in agreement with the observations [3,21]. Sensitivity analysis has been carried out to study the behavior of the parameters 1−λ, β, Hc, B (bluntness of the velocity profile) and μapp with the variation of D and HD.