Miracle-dz/UniFAR-FTUs huggingface dataset:
Challenges on the road to a multicellular bioartificial liver

Over recent years, the progress in the development of a bioartificial liver (BAL) as an extracorporeal device or as a tissue engineered transplantable organ has been immense. However, many important BAL characteristics that are necessary to meet clinical demands have not been sufficiently addressed. This review describes the existing challenges in the development of a BAL for clinical applications, highlighting multicellularity and sinusoidal microarchitecture as crucial BAL characteristics to fulfil various liver functions. Currently available sources of nonparenchymal liver cells, such as endothelial cells, cholangiocytes and macrophages, used in BAL development are defined. Also, we discuss the recent studies on the reconstruction of the complex liver sinusoid microarchitecture using various liver cell types. Moreover, we highlight some other aspects of a BAL, such as liver zonation and formation of a vascular as well as biliary network for an adequate delivery, biotransformation and removal of substrates and waste products. Finally, the benefits of a multicellular BAL for the pharmaceutical industry are briefly described. Copyright © 2016 John Wiley & Sons, Ltd.
Deficits in Glenohumeral Passive Range of Motion Increase Risk of Elbow Injury in Professional Baseball Pitchers

Background: Injuries to the elbow joint in baseball pitchers appear common. There appears to be a correlation between shoulder range of motion and elbow injuries. Purpose: To prospectively determine whether decreased ROM of the throwing shoulder is correlated with the onset of elbow injuries in professional baseball pitchers. Study Design: Cohort study; Level of evidence, 2. Methods: For 8 consecutive years (2005-2012), passive range of motion of both the throwing and nonthrowing shoulders of all major and minor league pitchers within a single professional baseball organization were measured by using a bubble goniometer during spring training. In total, 505 examinations were conducted on 296 pitchers. Glenohumeral external rotation and internal rotation were assessed in the supine position with the arm at 90° of abduction and in the plane of the scapula. The scapula was stabilized per methods previously established. Total rotation was defined as the sum of external rotation and internal rotation. Passive shoulder flexion was assessed with the subject supine and the scapula stabilized per methods previously established. Elbow injuries and days missed because of elbow injuries were assessed and recorded by the medical staff of the team. Throwing and nonthrowing shoulder measurements were compared by using Student t tests; 1-tailed Fisher exact tests were performed to identify significant associations between shoulder motion and elbow injury. Nominal logistic regression was performed to determine the odds of elbow injury. Results: Significant differences were noted during side-to-side comparisons within subjects. There were 49 elbow injuries and 8 surgeries in 38 players, accounting for a total of 2551 days missed. Neither glenohumeral internal rotation deficit nor external rotation insufficiency was correlated with elbow injuries. Pitchers with deficits of >5° in total rotation in their throwing shoulders had a 2.6 times greater risk for injury. Pitchers with deficit of ≥5° in flexion of the throwing shoulder had a 2.8 times greater risk for injury. Conclusion: Bilateral differences in shoulder total rotation and flexion had a significant effect on the risk for elbow injuries in pitchers. Clinicians need to be aware of these findings and plan preventive programs that address these issues in hopes of reducing elbow injuries.
Angiogenic and osteogenic regeneration in rats via calcium phosphate scaffold and endothelial cell co‐culture with human bone marrow mesenchymal stem cells (MSCs), human umbilical cord MSCs, human induced pluripotent stem cell‐derived MSCs and human embryonic stem cell‐derived MSCs

Angiogenesis is a limiting factor in regenerating large bone defects. The objective of this study was to investigate angiogenic and osteogenic effects of co‐culture on calcium phosphate cement (CPC) scaffold using human umbilical vein endothelial cells (hUVECs) and mesenchymal stem cells (MSCs) from different origins for the first time. hUVECs were co‐cultured with four types of cell: human umbilical cord MSCs (hUCMSCs), human bone marrow MSCs (hBMSCs) and MSCs from induced pluripotent stem cells (hiPSC‐MSCs) and embryonic stem cells (hESC‐MSCs). Constructs were implanted in 8 mm cranial defects of rats for 12 weeks. CPC without cells served as control 1. CPC with hBMSCs served as control 2. Microcapillary‐like structures were successfully formed on CPC in vitro in all four co‐cultured groups. Microcapillary lengths increased with time (p < 0.05). Osteogenic and angiogenic gene expressions were highly elevated and mineralization by co‐cultured cells increased with time (p < 0.05). New bone amount and blood vessel density of co‐cultured groups were much greater than controls (p < 0.05) in an animal study. hUVECs co‐cultured with hUCMSCs, hiPSC‐MSCs and hESC‐MSCs achieved new bone and vessel density similar to hUVECs co‐cultured with hBMSCs (p > 0.1). Therefore, hUCMSCs, hiPSC‐MSCs and hESC‐MSCs could serve as alternative cell sources to hBMSCs, which require an invasive procedure to harvest. In conclusion, this study showed for the first time that co‐cultures of hUVECs with hUCMSCs, hiPSC‐MSCs, hESC‐MSCs and hBMSCs delivered via CPC scaffold achieved excellent osteogenic and angiogenic capabilities in vivo. The novel co‐culture constructs are promising for bone reconstruction with improved angiogenesis for craniofacial/orthopaedic applications. Copyright © 2017 John Wiley & Sons, Ltd.
Efficient transdifferentiation of human dermal fibroblasts into skeletal muscle

Skeletal muscle holds significant regenerative potential but is incapable of restoring tissue loss caused by severe injury, congenital defects or tumour ablation. Consequently, skeletal muscle models are being developed to study human pathophysiology and regeneration. Their physiological accuracy, however, is hampered by the lack of an easily accessible human cell source that is readily expandable and capable of efficient differentiation. MYOD1, a master gene regulator, induces transdifferentiation of a variety of cell types into skeletal muscle, although inefficiently in human cells. Here we used MYOD1 to establish its capacity to induce skeletal muscle transdifferentiation of human dermal fibroblasts under baseline conditions. We found significant transdifferentiation improvement via transforming growth factor‐β/activin signalling inhibition, canonical WNT signalling activation, receptor tyrosine kinase binding and collagen type I utilization. Mechanistically, manipulation of individual signalling pathways modulated the transdifferentiation process via myoblast proliferation, lowering the transdifferentiation threshold and inducing cell fusion. Overall, we used transdifferentiation to achieve the robust derivation of human skeletal myotubes and have described the signalling pathways and mechanisms regulating this process. Copyright © 2017 John Wiley & Sons, Ltd.
Collagen density gradient on three‐dimensional printed poly(ε‐caprolactone) scaffolds for interface tissue engineering

The ability to engineer scaffolds that resemble the transition between tissues would be beneficial to improve repair of complex organs, but has yet to be achieved. In order to mimic tissue organization, such constructs should present continuous gradients of geometry, stiffness and biochemical composition. Although the introduction of rapid prototyping or additive manufacturing techniques allows deposition of heterogeneous layers and shape control, the creation of surface chemical gradients has not been explored on three‐dimensional (3D) scaffolds obtained through fused deposition modelling technique. Thus, the goal of this study was to introduce a gradient functionalization method in which a poly(ε‐caprolactone) surface was first aminolysed and subsequently covered with collagen via carbodiimide reaction. The 2D constructs were characterized for their amine and collagen contents, wettability, surface topography and biofunctionality. Finally, chemical gradients were created in 3D printed scaffolds with controlled geometry and porosity. The combination of additive manufacturing and surface modification is a viable tool for the fabrication of 3D constructs with controlled structural and chemical gradients. These constructs can be employed for mimicking continuous tissue gradients for interface tissue engineering.
Human adipose tissue‐derived tenomodulin positive subpopulation of stem cells: A promising source of tendon progenitor cells

Cell‐based therapies are of particular interest for tendon and ligament regeneration given the low regenerative potential of these tissues. Adipose tissue is an abundant source of stem cells, which may be employed for the healing of tendon lesions. However, human adult multipotent adipose‐derived stem cells (hASCs) isolated from the stromal vascular fraction of adipose tissue originate highly heterogeneous cell populations that hinder their use in specific tissue‐oriented applications. In this study, distinct subpopulations of hASCs were immunomagnetic separated and their tenogenic differentiation capacity evaluated in the presence of several growth factors (GFs), namely endothelial GF, basic‐fibroblast GF, transforming GF‐β1 and platelet‐derived GF‐BB, which are well‐known regulators of tendon development, growth and healing. Among the screened hASCs subpopulations, tenomodulin‐positive cells were shown to be more promising for tenogenic applications and therefore this subpopulation was further studied, assessing tendon‐related markers (scleraxis, tenomodulin, tenascin C and decorin) both at gene and protein level. Additionally, the ability for depositing collagen type I and III forming extracellular matrix structures were weekly assessed up to 28 days. The results obtained indicated that tenomodulin‐positive cells exhibit phenotypical features of tendon progenitor cells and can be biochemically induced towards tenogenic lineage, demonstrating that this subset of hASCs can provide a reliable source of progenitor cells for therapies targeting tendon regeneration.
A Methylaspartate Cycle in Haloarchaea

Salt-loving microbes have patched together an alternative carbon assimilation cycle. Access to novel ecological niches often requires adaptation of metabolic pathways to cope with new environments. For conversion to cellular building blocks, many substrates enter central carbon metabolism via acetyl–coenzyme A (acetyl-CoA). Until now, only two such pathways have been identified: the glyoxylate cycle and the ethylmalonyl-CoA pathway. Prokaryotes in the haloarchaea use a third pathway by which acetyl-CoA is oxidized to glyoxylate via the key intermediate methylaspartate. Glyoxylate condensation with another acetyl-CoA molecule yields malate, the final assimilation product. This cycle combines reactions that originally belonged to different metabolic processes in different groups of prokaryotes, which suggests lateral gene transfer and evolutionary tinkering of acetate assimilation. Moreover, it requires elevated intracellular glutamate concentrations, as well as coupling carbon assimilation with nitrogen metabolism.
Biomimetic design of musculoskeletal humanoid knee joint with patella and screw-home mechanism

We are trying to create a novel musculoskeletal humanoid robot which has a humanlike structure. In this paper, we present a new knee joint which is usually simplified in robotics for high controllability. The knee joint has three human mimetic points, patella, screw-home mechanism and four-linked linkage. Patella is for a longer moment arm. Screw-home mechanism is for locking knee joint. Four-linked linkage is for making humanlike motion. Furthermore, we confirmed those performances by three experiments.
Human osteoarthritic chondrons outnumber patient‐ and joint‐matched chondrocytes in hydrogel culture—Future application in autologous cell‐based OA cartilage repair?

Autologous chondrocyte implantation (ACI) is used in 34–60% for osteoarthritic (OA) cartilage defects, although ACI is neither recommended nor designed for OA. Envisioning a hydrogel‐based ACI for OA that uses chondrons instead of classically used chondrocytes, we hypothesized that human OA chondrons may outperform OA chondrocytes. We compared patient‐ and joint surface‐matched human OA chondrons with OA chondrocytes cultured for the first time in a hydrogel, using a self‐assembling peptide system. We determined yield, viability, cell numbers, mRNA expression, GAPDH mRNA enzyme activity, Collagen II synthesis (CPII) and degradation (C2C), and sulfated glycosaminoglycan. Ex vivo, mRNA expression was comparable. Over time, significant differences in survival led to 3.4‐fold higher OA chondron numbers in hydrogels after 2 weeks (p = .002). Significantly, more enzymatically active GAPDH protein indicated higher metabolic activity. The number of cultures that expressed mRNA for Collagen Types I and VI, COMP, aggrecan, VEGF, TGF‐β1, and FGF‐2 (but not Collagen Types II and X) was different, resulting in a 3.5‐fold higher number of expression‐positive OA chondron cultures (p < .05). Measuring CPII and C2C per hydrogel, OA chondron hydrogels synthesized more than they degraded Collagen Type II, the opposite was true for OA chondrocytes. Per cell, OA chondrons but not OA chondrocytes displayed more synthesis than degradation. Thus, OA chondrons displayed superior biosynthesis and mRNA expression of tissue engineering and phenotype‐relevant genes. Moreover, human OA chondrons displayed a significant survival advantage in hydrogel culture, whose presence, drastic extent, and timescale was novel and is clinically significant. Collectively, these data highlight the high potential of human OA chondrons for OA ACI, as they would outnumber and, thus, surpass OA chondrocytes.
Social inclusion and choice for adults with learning disabilities: Some lessons from reprovisioning

Based on a study of the relocation of adults with learning disabilities from a local authority hostel to individual and multi-occupancy tenancies, this article argues that well-intentioned reprovisioning policy initiatives struggle to strike a balance between imperatives concerned with managing the state's duty of care, realising social inclusion and securing the rights of individuals. Protracted implementation and changes to the timetable contributed to tension between speed and meaningful consultation and adversely affected the perceived reliability of information. Many residents, staff and relatives were neither clear about the reasons for change, nor were supportive of it. Initial scepticism amongst staff and relatives changed over time to appreciation of the value of the move and frequency of contact between tenants and relatives remained relatively stable. However, the shift from unit-based management to that of dispersed tenancies put staff autonomy, support and supervision under scrutiny. More fundamentally, the choices available to users were restricted to matters of daily living and routine and few staff felt enabled to support them to take full advantage of the move.
Keypoints based laser scan matching — A robust approach

This paper aims at development of a robust keypoints based scan matching (KSM) methodology for 2D laser data applied to mobile robot navigation. In this method feature points are first transformed to grid points, and then represented in the form of image. Keypoints are extracted using Harris corner detection method and finally matching is done by RANSAC method. Real world experiments have been carried out to evaluate the utility and robustness of the proposed method. A comparison has been drawn with scan matching technique with ICP method. The proposed method might be used in a robust manner for mobile robot navigation with moderate computational complexity.
Decellularized caprine liver extracellular matrix as a 2D substrate coating and 3D hydrogel platform for vascularized liver tissue engineering

Development of a vascularized liver tissue construct is a need of an hour to circumvent the current demand of liver transplantation in health care sector. An appropriate matrix must support liver cell viability, functionality, and development of microvasculature. With this perspective, here, we report the use of decellularized caprine liver extracellular matrix (CLECM) derived hydrogel for tissue engineering applications. First, CLECM was used as a substrate coating material for 2D hepatocyte culture. HepG2 cells cultured on CLECM‐coated surface showed higher albumin, urea, glycogen, and GAGs synthesis in comparison with collagen‐coated surface (taken as control for the study). Thereafter, the cells were encapsulated in CLECM hydrogels for 3D culture. In CLECM hydrogels, HepG2 cells showed highly differentiated and polarized phenotype with the appearance of bile canaliculi‐like structures and enhanced expression of mature hepatocyte markers. We further showed that CLECM hydrogels also supported the development of microvasculature in vitro, thus making it a suitable candidate for development of a prevascularized liver tissue construct. In conclusion, we proved the superiority of CLECM over collagen for 2D/3D human hepatocyte and endothelial cell culture. CLECM could serve as an efficient biomaterial platform in the development of a liver tissue construct for application in tissue engineering.
A robust adaptive neural controller to drive a knee joint actuated orthosis

This paper presents a robust adaptive control of an actuated orthosis intended to assist the lower limb movements of dependent persons. The proposed controller, based on a MultiLayer Perception Neural Network (MLPNN) and considered as a black-box, does not require the dynamic model of lower limbs/orthosis. A neural identification is used to extract the principal components of the MLPNN input vector. The MLPNN is used to compensate the dynamic effects arising from the interaction between the human lower limb and the orthosis. MLPNN weights are adjusted online according to an adaption algorithm based on the Lyapunov analysis. Experiments, carried out on a healthy subject, show the good performance of the proposed controller in terms of trajectory tracking and robustness against external disturbances.
Mineralization of gellan gum hydrogels with calcium and magnesium carbonates by alternate soaking in solutions of calcium/magnesium and carbonate ion solutions

Mineralization of hydrogels is desirable prior to applications in bone regeneration. CaCO3 is a widely used bone regeneration material, and Mg, when used as a component of calcium phosphate biomaterials, has promoted bone‐forming cell adhesion and proliferation and bone regeneration. In this study, gellan gum hydrogels were mineralized with carbonates containing different amounts of calcium (Ca) and magnesium (Mg) by alternate soaking in, firstly, a calcium and/or magnesium ion solution and, secondly, a carbonate ion solution. This alternate soaking cycle was repeated five times. Five different calcium and/or magnesium ion solutions, containing different molar ratios of Ca to Mg ranging from Mg free to Ca free were compared. Carbonate mineral formed in all sample groups subjected to the alternate soaking cycle. Ca : Mg elemental ratio in the mineral formed was higher than in the respective mineralizing solution. Mineral formed in the absence of Mg was predominantly CaCO3 in the form of a mixture of calcite and vaterite. Increasing the Mg content in the mineral formed led to the formation of magnesian calcite and decreased the total amount of the mineral formed and its crystallinity. Hydrogel mineralization and increasing Mg content in mineral formed did not obviously improve proliferation of MC3T3‐E1 osteoblast‐like cells or differentiation after 7 days.
Anterior Cruciate Ligament Function in Providing Rotational Stability Assessed by Medial and Lateral Tibiofemoral Compartment Translations and Subluxations

Background: Rotational knee stability provided by the anterior cruciate ligament (ACL) in the pivot-shift phenomena involves analysis of more complex robotic testing profiles and resulting tibiofemoral compartment kinematics and subluxations. Hypotheses: Using anterior-posterior tibial forces along with internal and valgus tibial moments will produce a major anterior subluxation of both tibiofemoral compartments not obtained with internal and valgus moments alone. Increasing the internal torque in pivot-shift testing will constrain the anterior subluxations of the medial and central tibial compartments. Study Design: Controlled laboratory study. Methods: A 6 degrees of freedom robotic knee testing system applied anterior translation and rotational loading profiles in 10 cadaveric knees before and after ACL sectioning. Changes in knee motion limits were measured, and medial and lateral tibiofemoral compartment translations were determined by digitization of tibial plateau anatomic landmarks. Loading profiles simulated Lachman and tibial rotation tests as well as typical pivot-shift loading profiles from prior in vitro and in vivo studies. Results: After ACL sectioning, anterior tibial translation increased by 10.3 ± 3.7 mm at 25° of flexion (P < .001). Internal tibial rotation increased by 1.6° ± 1.1° (5 N·m; P > .05). In pivot-shift tests (anterior translation, 100 N; internal rotation, 1 N·m; valgus, 7 N·m), the tibial rotation center shifted outside the medial tibial margin, with abnormal anterior translation of both compartments (medial, 12.9 ± 3.9 mm; lateral, 7.5 ± 3.7 mm; P < .001), with internal rotation decreasing by 4.1° ± 3.5° (P < .05). A greater internal rotation torque (5 vs 1 N·m) in the pivot-shift test constrained and limited anterior tibial translation and prevented anterior subluxation of the medial compartment (P < .001). Conclusion: Sectioning of the ACL produces major increases in tibiofemoral compartment translations and only small increases in internal tibial rotation. The simulation of the pivot shift requires a combined loading profile of anterior translation, internal rotation, and valgus, which produces the greatest anterior subluxation of the medial and lateral tibiofemoral compartments. This testing profile is recommended to be included along with other loading profiles for future ACL studies. The application of a high internal rotation torque in cadaveric pivot-shift tests constrains anterior tibial subluxation of the medial and center compartments and appears less ideal for analysis of ACL function and graft reconstructions. Clinical Relevance: Surgeons should be cautious in interpreting conclusions on ACL function and graft reconstructions without knowing the resulting tibiofemoral subluxations or loading conditions that may limit maximum anterior tibial femoral subluxations.
Common neurological and musculoskeletal problems in rabbits

NEUROLOGICAL and musculoskeletal disease is often encountered in pet rabbits, with head tilt and hindlimb paresis/paralysis being the most common clinical presentations. Arthritis is also a frequent finding in older animals. The principal causes of neurological disease in rabbits include bacterial infections, such as pasteurellosis, encephalitozoonosis, trauma and toxaemia. Accurate case assessment and diagnosis of neurological and musculoskeletal problems in this species can be a challenge for the veterinary surgeon in practice. However, with the increased availability of advanced diagnostic imaging techniques, such as computed tomography, obtaining a final diagnosis is a realistic goal. This article discusses the diagnostic procedures that can be used to investigate neurological and musculoskeletal problems in rabbits, and outlines the causes and management options for the most common conditions seen.