bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence of Bath Environment on the Fluid Content of Human and Rabbit Patellar Tendons
Authors: Israel Rajakumar , Atkinson Theresa 
Published: November 2021

Abstract
Recent studies have shown that the mechanical properties of tendons and ligaments are dependent on the amount of fluid present in the tissue. These studies have used a variety of bath environments to maintain or alter the fluid content of the tissue. However, no study has measured the effect of these baths on the fluid content of the specimen. In addition, no study has documented the influence of test environment on sectioned versus whole specimens. This experiment investigated the effect of saline, distilled water and sucrose baths on human and rabbit patellar tendons. Specimens were placed into the baths, and weight gain over time was measured. The results show that all specimens gained weight, and thus fluid, over time. The results further show that human specimens absorbed fluid at a faster rate than rabbit specimens. An important conclusion of this study is that exposure time in a bath is a critical factor in tissue hydration. Significant differences in absorption rates between divided and whole specimens were also found.
Finite Element Study of Oxygen Diffusion in the Intervertebral Disc
Authors: Sélard E. , Shirazi-Adl A. , Urban J. P. G. 
Published: November 2021

Abstract
The intervertebral disc consists of a water-rich extra-cellular matrix which is synthesized and maintained by its cells. The disc is the largest avascular tissue in the body with its cells lying as much as 8mm away from the blood supply. Nutrients, essential for maintaining cellular viability, diffuse through the matrix from blood supply under a concentration gradient arising from cellular demand. The oxygen concentration gradients in the intervertebral disc are investigated to examine the effects of exchange area and disc thickness on oxygen flux in the disc. The concentration gradients are computed using the two-dimensional Poisson’s equation and measured values for oxygen consumption rate and oxygen diffusion.
Pore Growth in Foamed Intermetallics for Structural Implants
Authors: Ilegbusi Olusegun J. , Ballas Matthew W. 
Published: November 2021

Abstract
The hydrodynamically controlled growth of closely spaced bubbles in a semi-solid alloy matrix is investigated. Specific attention is given to the case of controlled pore growth during the formation of porous intermetallics. Growth models are derived using three distinct relationships for the rheology of semi-solid alloys at various solid fractions. A cell model is used to represent the effect of spacing on bubble growth. The resulting models are solved numerically and compared for a variety of cases.
Mechanical Failure of Artificial Joint Materials: Wear and Fatigue
Authors: Topoleski L. D. Timmie 
Published: November 2021

Abstract
Total artificial joint replacements are one of the most effective treatments for arthritis. Artificial joints are used to replace damaged cartilage and act as low-friction articulating materials in joints. During normal human walking, some of the materials used for artificial knee and hip replacements are subjected to both sliding articulation (relative motion) and cyclic loading. A common example is the CoCrMo alloy femoral surface of an artificial knee that articulates against an ultra-high-molecular-weight-polyethylene (UHMWPE) component. Other materials do not experience relative motion (at least not intentionally) and are subjected to only cyclic loading. An example is the poly(methyl methacrylate) or PMMA bone cement used to fix components of artificial joints into bones. In the case of articulating materials, both surfaces are susceptible to wear, from both second-body and third body (in the presence of abrasive particles) mechanisms. Wear of the UHMWPE has received considerable attention recently, since the polymer wear is far more obvious than the metal wear. The Biomaterials field is developing an understanding of the wear mechanisms and how to enhance the wear resistance of UHMWPE. The wear of the metal components has not received as much attention, yet materials wear as a couple; both surfaces play a role in the overall wear. In the UMBC Laboratory for Implantable Materials, we are investigating the mechanisms of CoCrMo alloy wear, and the effect of worn metal components on the wear of UHMWPE. Understanding the wear mechanisms of metal components may help to extend the life of artificial joints by allowing new articulating material combinations and joint designs. For non-articulating materials, fatigue failure is a primary concern. Fatigue of metal components is relatively rare. In the distal portion of an artificial hip, the metal hip stem is fixed into the bone by a layer of PMMA bone cement. The PMMA bone cement is far weaker and less resistant to fracture and fatigue than either the bone or the metal, and thus may be considered the mechanical “weak link” in cemented total joints. We are investigating the fatigue properties of PMMA bone cements, and studying the mechanisms of fatigue crack initiation. If we can determine how fatigue cracks start in bone cement, we may be able to develop, for example, new surgical procedures (e.g., bone preparation) that will reduce the likelihood of fatigue failure. New formulations of bone cement have been developed for both joint fixation, and also for bone repair or replacement. Understanding the failure mechanisms of bone cements may enable safe and effective new uses for new bone cements, and extend the lives of cemented artificial joints.
Metal Release From Ti-6Al-4V Posterior Cervical Spine Plates: A Computational and Experimental Study in the Canine Model
Authors: Villarraga Marta L. 
Published: November 2021

Abstract
The use of Ti-6Al-4V for spinal implants has increased due to its advantageous mechanical properties, biocompatibility, corrosion resistance, and compatibility with MRI procedures. The release of metal ions or particulates, which can result from mechanical loads imposed on the implant, can affect the degree of biocompatibility of spinal implants, possibly influencing their clinical performance. In this project, the titanium metal release from Ti-6Al-4V posterior cervical spine plates was examined using a computational and experimental approach in the canine model.
Laser Microtexturing of Implant Surfaces for Enhanced Tissue Integration
Authors: Ricci John L. , Alexander Harold 
Published: November 2021

Abstract
Dental and orthopaedic implants rely on combinations of bone and soft tissue integration for mechanical support. While polished metal surfaces have been shown to encourage fibrous tissue encapsulation, roughened surfaces encourage bone integration. It is an accepted practice to roughen or texture regions of implants to encourage bone integration and produce smooth regions to promote soft tissue integration. We have developed a laser microtexturing technique that can be used to produce precision microtextured surfaces.
Abrasion of Steel by Diamondlike Carbon Coatings
Authors: Harris Stephen J. 
Published: November 2021

Abstract
Thin ceramic coatings can increase the fatigue lifetime of bearings and gears, possibly by polishing their counterparts and reducing stresses from asperities. Thus, a coating’s ability to polish or abrade may determine its usefulness. Yet there has been little work examining factors which control the abrasiveness of such coatings. We have analyzed the abrasiveness of diamondlike carbon and boron carbide coatings against steel for this study. We find an extremely steep dependence of abrasiveness on hardness. We show that coating roughness with horizontal features on the nanometer-scale is strongly correlated with abrasiveness, while roughness with horizontal features on the micron-scale is not correlated with abrasiveness. The nano-scale—but not the micro-scale—structure is quickly obliterated by sliding against steel, explaining the drastic reduction with time in the abrasiveness of the coating that we observe. We derive quantitative scaling relationships that show how the time dependence of the abrasion rate varies with important parameters of sliding wear, and we use these relationships to predict abrasion kinetics for new experiments. Detailed modeling of the stresses present during abrasion leaves some important questions unanswered.
Kinetic Spray: A New Coating Process
Authors: van Steenkiste T. 
Published: November 2021

Abstract
A relatively new coating process that uses high velocity gas to accelerate powder particles to velocities on the order of 500 m/s is being used to produce low porosity, low oxide, and low residual stress coatings. The powder particles are not melted or thermally softened prior to impact with the substrate. The coating process depends primarily on the conversion of the particle’s kinetic energy to mechanical and thermal deformation when the incident powder particles impact the substrate surface at high velocity. The time scale for the particle deformation and subsequent bonding to the substrate is on the order of 100 to 400 nsec. This extremely short time scale limits the possible bonding mechanisms and various papers have speculated on the possible bonding mechanisms for these coatings. An overview of the kinetic spray process, the history, description of the equipment, as well as an explanation of the bonding mechanism will be presented.
The Anisotropic Elastic Constants of Cancellous Bone
Authors: Cowin Stephen C. 
Published: November 2021

Abstract
A method of data analysis for a set of elastic constant measurements is applied to an excellent data base for cancellous bone. For these materials the identification of the type of elastic symmetry is complicated by the variable composition of the material. The data analysis method permits the identification of the type of elastic symmetry to be accomplished independent of the examination of the variable composition. This method of analysis may be applied to any set of elastic constant measurements, but is illustrated here by application to an extraordinary data base of cancellous bone elastic constants. The solid volume fraction or bulk density is the compositional variable for the elastic constants of these natural materials. The final results are the solid volume fraction dependent orthotropic Hooke’s law for cancellous bone.
VCN-01 disrupts pancreatic cancer stroma and exerts antitumor effects
Authors: Bazan-Peregrino Miriam , Garcia-Carbonero Rocio , Laquente Berta , Álvarez Rafael , Mato-Berciano Ana , Gimenez-Alejandre Marta , Morgado Sara , Rodríguez-García Alba , Maliandi Maria V , Riesco M Carmen , Moreno Rafael , Ginestà Mireia M , Perez-Carreras Mercedes , Gornals Joan B , Prados Susana , Perea Sofía , Capella Gabriel , Alemany Ramon , Salazar Ramon , Blasi Emma , Blasco Carmen , Cascallo Manel , Hidalgo Manuel 
Published: November 2021

BackgroundPancreatic ductal adenocarcinoma (PDAC) is characterized by dense desmoplastic stroma that limits the delivery of anticancer agents. VCN-01 is an oncolytic adenovirus designed to replicate in cancer cells with a dysfunctional RB1 pathway and express hyaluronidase. Here, we evaluated the mechanism of action of VCN-01 in preclinical models and in patients with pancreatic cancer.MethodsVCN-01 replication and antitumor efficacy were evaluated alone and in combination with standard chemotherapy in immunodeficient and immunocompetent preclinical models using intravenous or intratumoral administration. Hyaluronidase activity was evaluated by histochemical staining and by measuring drug delivery into tumors. In a proof-of-concept clinical trial, VCN-01 was administered intratumorally to patients with PDAC at doses up to 1×1011viral particles in combination with chemotherapy. Hyaluronidase expression was measured in serum by an ELISA and its activity within tumors by endoscopic ultrasound elastography.ResultsVCN-01 replicated in PDAC models and exerted antitumor effects which were improved when combined with chemotherapy. Hyaluronidase expression by VCN-01 degraded tumor stroma and facilitated delivery of a variety of therapeutic agents such as chemotherapy and therapeutic antibodies. Clinically, treatment was generally well-tolerated and resulted in disease stabilization of injected lesions. VCN-01 was detected in blood as secondary peaks and in post-treatment tumor biopsies, indicating virus replication. Patients had increasing levels of hyaluronidase in sera over time and decreased tumor stiffness, suggesting stromal disruption.ConclusionsVCN-01 is an oncolytic adenovirus with direct antitumor effects and stromal disruption capabilities, representing a new therapeutic agent for cancers with dense stroma.Trial registration numberEudraCT number: 2012-005556-42 andNCT02045589.
10 Tertiary lymphoid structure in pancreatic ductal adenocarcinoma; a potential target in an immunologically inert malignancy
Authors: Adoke Kasimu , Haruna Sanusi 
Published: November 2021

BackgroundTertiary lymphoid structure (TLS) are immune aggregates with various degrees of organization that forms outside of secondary lymphoid organ in response to chronic inflammation, infection or tumours.1 2 TLS like secondary lymphoid organ, has defined T cell zones, B cell zones, high endothelial venules (HEV) and matured dendritic cells. They have been shown to correlate with increase patient survival in many tumours. Pancreatic ductal carcinoma (PDAC) is generally believed to be immunologically inert, low tumour mutation burden (TMB) and poor response to checkpoint blockade. Recent findings in some patients with PDAC shows significant intratumoral cytotoxic T cell infiltration and a high Inflammatory signature. Since current immunotherapy aim to enhance CD 8+ T cells, we aim to investigate the contribution of humoral immunity in patients with TLS in PDAC.MethodsTissue blocks were obtained from departmental archive and sections were cut and stained with routine H&E of all patients who underwent surgery for pancreatic cancer from 2015–2021 at Federal Medical Centre Birnin Kebbi. Serial sections were done at 5µ and four immunohistochemical stains CD 3, CD8, CD20 and PD-L1 were used. Statistical analysis was done using spss version 24.ResultsA total of nine cases of PDAC were diagnosed during the period with a Male Female ratio of 1:1.25 with an age range of 40–68 years and a mean age of 57.7±8.4. Five cases (55.6%) of PDAC showed TLS with marked expression of CD20 B+ cells seen in all five cases (figures 1 and 2). Also expressed are CD 8+ cytotoxic T cells and PD-L1. Prognosis was better in patients with TLS compare with those without TLS.Abstract 10 Figure 1TLS in pancreatic ductal adenocarcinoma.Abstract 10 Figure 2CD 20 stain in TLSConclusionsTLS can be a potential therapeutic target to explore in the future for treatment of some cancers including PDAC through induction of TLS formation in inert tumours or B lymphocyte specific target.ReferencesPitzalis C, Jones GW, Bombardieri M, Jones S. Ectopic lymphoid like structures in infection, cancer and autoimmunity. Nat Rev Immunol 2014; 14: 447–462.Neyt K, Perros F, Geurtsvan C, Hammad H. Lambrecht B. Tertiary lymphoid organs in infection and autoimmunity. Trends Immunol 2012; 33: 297–305.Ethics ApprovalEthical Approval was obtained for this study with Ethics number KSHREC Registration Number:104:6/2019ConsentN/A
57 Assessment of the spatial distribution of B cells subpopulations in the tumor microenvironment and tertiary lymphoid structures by Brightplex®, a sequential chromogenic multiplex assay
Authors: Trinh Alex , Collignon Aurélie , Olive Marion , Jaume Clémence , Chamourin Maïté , Sfeir Nour , Anselmo Dylan , Ramouz-Charpentier Raana , Culey Georgia , Haond Christophe , Galon Jerome , Fieschi-Meric Jacques 
Published: November 2021

BackgroundDensity and localization of T cells within the tumor microenvironment (TME) is critical to control tumor growth. Immunotherapy with antibodies against immune checkpoint inhibitors (ICI), which aim to reinvigorate exhausted T cells, despite inducing long-term response in many cancer types, remains ineffective for most patients. Other factors present in the TME may participate in the control of tumors, among several candidates, the role of B cells has been underestimated. Publications revealed that B-cells are associated with good prognosis in several indications. However, there are no general rules since neutral or even deleterious impact of the presence of B-cells in the tumor was reported. Among other hypotheses, we can suppose that the level of activation and isotype switch will be important to mediate activation of NK cells or ADCC within the tumor and will have a favorable impact on the prognosis. In addition, the spatial distribution of B-cells may be important since, in the TME, they are mostly located in Tertiary Lymphoid Structures (TLS) which are ectopic lymphoid organs. Mature TLSs contain zones where dendritic cells (DC) present antigen to T-cells and others where proliferating B-cells undergo class switch and maturation toward plasma cells. Antigen presentation by B cells to T cells is supported by DCs, therefore, the presence of these three types of cells within the TLS allows T cell activation in the TME. If B-cells are major players in the therapeutic efficacy of ICI antibodies, not all subtypes of tumor infiltrating B-cells are likely to participate in response to immunotherapy.MethodsTo decipher the roles of B cells, new tools are needed to identify the differentiation and activation status of individual B cells. We have developed a 7-plex panel of antibodies against biomarkers that allow the identification of main types of B cells.ResultsOn a single FFPE tissue section: naïve, unswitched memory, switched memory, activated, plasmablast and plasma B cells, as well as T cells and DC are identified. Following images registration, complex cells phenotypes can be detected and quantified. Furthermore, digital pathology tools allow the evaluation of the spatial distribution within the TME of subtypes of B cells especially in association with TLSs.ConclusionsThis new tool unravels the heterogeneity of B cells in TME and could help clinical researchers to understand their contribution to the response to immunotherapy. Integrated into an Immunogram, this new Brightplex® Panel will be critical to understand the immune contexture of the tumor.
316 Leucine-rich repeats and immunoglobulin-like domains protein 1 is highly expressed on tumor-infiltrating T cells and may play a role in modulating T cell activation
Authors: Wang Li , Chan Timothy , Gilmour Cassandra , Zhang Keman , Alban Tyler , Ta Hieu , Ta Hieu 
Published: November 2021

BackgroundImmune checkpoint receptors (ICRs) regulate T cell-mediated immune responses to self - and neo-antigens, thereby play an important role in the development of autoimmunity and immune responses to infections. In cancer, ICRs such as PD-1 and CTLA4 impair immuno-surveillance against neoplastic cells, while other costimulatory molecules like ICOS, OX40 could augment the immune responses. Immunotherapy that targets either inhibitory or costimulatory immune checkpoint have become the breakthrough therapy for cancer treatment. However, the efficacy of this class of therapy is limited to a fraction of patients, pointing the need to overcome non-redundant immuno-inhibitory pathways or discover new immuno-costimulatory pathways.MethodsExamining surface proteins that are highly expressed in various mouse tumors by flow cytometry and immuno-histochemistryResultsThis study identified the expression of Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) in activated CD4+ and CD8+ T cells. LRIG1 is a type-I transmembrane protein with 1092 amino acids (120 kD) and ubiquitous tissue expression patterns. We show that LRIG1 expression is not detectable on naïve CD4+ and CD8+ murine T cells but is induced upon T cell receptor (TCR) stimulation in vitro, and in tumor-infiltrating lymphocytes (TILs) from multiple murine models. We also detected LRIG1 expression on CD4+ and CD8+ TILs in several types of cancer patients such as non-small-cell lung cancer, breast cancer, melanoma, B cell lymphoma.ConclusionsLRIG1 was originally identified as a tumor suppressor gene in a variety of tissues, but its expression and function have not been explored in immune cells. Our data suggest that LRIG1 is highly expressed in TILs in multiple cancer types and might play a role in regulating the anti-tumor immune responseEthics ApprovalOur studies have been approved by the ethics committee of the Cleveland Clinic.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
317 An immunosuppressive tumor population drives global and regional patterns of immune infiltration in heterogeneous tumors
Authors: Tanaka Miho , Lum Lotus , Ng Kenneth , Adams Zoe , Superville Daphne , Reeves Melissa 
Published: November 2021

BackgroundIntratumoral heterogeneity (ITH) is cellular and molecular diversity within a tumor. ITH is linked to failure of immunotherapy in multiple cancer types. One of the suggested mechanisms of this failure is the absence of a productive immune response, which can be driven by the dominance of a tumor population that creates immunosuppressive microenvironment. However, the molecular mechanisms that mediate such dominant immunosuppressive effects and how a dominant immunosuppressive tumor population affects the efficacy of immune checkpoint blockade (ICB) therapy are poorly understood.MethodsWe generated a library of squamous skin cell carcinoma cell lines derived from DMBA+TPA carcinogen-treated mice. Upon transplantation into immunocompetent mice, two cell lines (CF6 and CF9) gave rise to highly and poorly immune-infiltrated tumors, respectively. These two cell lines were tagged with YFP and RFP, respectively, mixed at a 1:1 ratio and injected subcutaneously. The resulting mixed tumors contained a patchwork of distinct regions that are predominantly occupied with YFP (CF6) cells, occupied with RFP (CF9) cells, or are a mixture of YFP and RFP cells. These mixed tumors were microdissected into YFP, RFP, and mixed regions, and the immune infiltrate in each region was analyzed by flow cytometry.ResultsWe found mixed tumors were ”cold” on a whole-tumor level. However, regional analysis showed a higher frequency of total and CD4 T cells in YFP regions compared to RFP regions. In contrast, macrophages exhibited a preferential localization to RFP regions. This suggests that local factors unique to each region drive the immune infiltration patterns of CD4 T cells and macrophages. Interestingly, although CD8 T cells showed a low frequency in all regions, a majority of CD8 T cells from YFP regions produced IFNgamma in response to PMA/Ionomycin stimulation while IFNgamma+ CD8 T cells from RFP regions made up a small fraction. This suggests that the presence of CF9-RFP regions inhibits infiltration of CD8 T cells throughout the tumor, but may not affect the anti-tumoral potential of CD8 T cells that succeed in infiltrating CF6-YFP regions.ConclusionsAn immunosuppressive tumor population rendered our model heterogeneous tumors ”cold” on the whole. Nonetheless, we observed regional patterns in the quantity and quality of immune infiltrates, with local immune infiltration being shaped by the tumor cells present in that region. Understanding how these immune infiltration patterns impact the response of each region to ICB therapy will provide insights into the mechanism by which ITH poses barriers to immunotherapy.