bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of n‐Acetylcysteine on the Migration of Myofibroblasts
Authors: Nichols Matthew Dillon , Vaughan Melville B 
Published: November 2023

Dupuytren's contractures are hand deformities that affect more than 200,000 cases in the US per year and are typically cured by invasive procedures that remove the nodules that form on the affected hand. Our goal is to study chemical inhibition of myofibroblasts, cells associated with Dupuytren's contracture, to provide insight for a noninvasive treatment of Dupuytren's contractures. Myofibroblasts use migration as part of their pathologic activities. This study examined the migration of myofibroblasts, using varying amounts of the amino acid n‐acetylcysteine (NAC), previously shown to inhibit myofibroblast differentiation. The methods used were an elastomer plug migration assay and this determined the myofibroblast migration. Our results demonstrated NAC increased the speed of migration when used in concentrations of 1–5μM and NAC inhibited the migration when used in concentrations of 10–20μM. In a complex tissue, this biphasic result may have unintended consequences. Our future goal is to study the mechanism of this biphasic migration effect.Support or Funding InformationUCO Office of Research and Grants
Caffeine Inhibits Dupuytren's Fibroblast Form and Function In Vitro
Authors: Pantoja Joana C , Bryson Matthew , Alkadhem Niyaf , Vaughan Melville B. 
Published: November 2023

Myofibroblasts are contractile, secretory cells of wound healing, fibroses, and contractures. Recently caffeine was shown to reduce fibrotic conditions in rodents. Our goal was to determine caffeine's effect on Dupuytren's contracture cells in vitro. We cultured fibroblasts in three different experimental models for 5 days. Transforming Growth Factor‐beta (TGF‐b) was used to stimulate fibroblast differentiation into myofibroblasts. Replicate cultures were treated with 5mM caffeine using a coverslip assay. Immunostaining results showed that caffeine reduced proliferation and alpha‐smooth muscle actin. Stress fibers were present in both treated and untreated groups, suggesting the cells would be contractile. Fibroblasts plated in stress‐relaxed collagen lattices failed to generate any tension (3 cell types, n=4 each). We then cultured collagen lattices for 3 days to allow tension generation, followed by caffeine treatment. Caffeine failed to inhibit contraction under these conditions (n=4). Fibroblasts remodel and compress collagen using migration‐like tractional forces. We predicted that caffeine would inhibit cell migration. Using a migration assay we determined that 5mM caffeine inhibited migration. Therefore caffeine likely affects cellular pathways related to migration rather than contraction or tension generation. This suggests that treating already‐existing fibrotic conditions with caffeine will be more challenging than preventing future occurrences.Support or Funding InformationUCO Office of Research and Grants, NSF OK‐LSAMP Cooperative Agreement HRD‐0902027, and Fulbright Visiting Scholar Program for Iraq 2015
The Role of Nanoscale Roughness on Cell Attachment Following Titanium‐based Instrumentation of Titanium, Titanium‐Zirconium, and Zirconia Surfaces
Authors: Cerutis D. Roselyn , Fischer Nicholas G. , Gnabasik Ryan , Lang Melissa S. , Baruth Andrew 
Published: November 2023

This study aimed to evaluate the nanoscale characteristics of human gingival fibroblast (HGF) adhesion to disks composed of several dental implant and healing abutment materials following repeated (100x) instrumentation with a titanium (Ti) curette, as commonly used in dental implant surface cleaning, using atomic force microscopy (AFM) in contact mode. Sterile Ti Grade 2, Zirconia (ZrO2) and Ti‐zirconium (Ti‐Zr, Roxolid®) disks (Straumann®, Andover, MA, USA) with a machined surface, 5 mm in diameter, were used in this study. Optical laser profilometry (1 – 5 μm lateral resolution) over a length of 4.4 mm revealed a statistical increase (over control) in average roughness for Ti and Ti‐Zr, but not for ZrO2. The disks were then placed in 96‐well cell culture plates and seeded with 0.3 ml of an HGF suspension at a density of 104 cells / ml of cell culture media. The units were incubated for 24 h at 37 °C in a humidified CO2 incubator. The units were removed from the 96 well dishes, rinsed in phosphate buffered saline, fixed by immersion in 95% ethanol for 5 min, and air‐dried. Scanning electron microscopy revealed that HGF adhesion was statistically higher (over control) for Ti, Ti‐Zr, but not for ZrO2. We employed AFM (5 – 10 nm lateral resolution) to explicate the role of nanoscale roughness on cellular attachment; in particular, whether the nanoscale roughness played a dominant role in adhesion. AFM was performed on an Agilent 5420 SPM/AFM, in ambient conditions, housed in an acoustic and mechanical vibration isolation chamber and analyzed with Agilent's PicoView software package. Images were obtained in constant force mode with a 1 Hz scan rate, at 512 lines per image, with a Silicon Nitride cantilever (spring constant of 0.08 N/m and a tip radius of ≤ 10 nm). Images taken at size scales of 2 to 100 μm revealed an instrumented surface of Ti and Ti‐Zr that was coated with 50 – 100 nm pits and fissures, while ZrO2 remained relatively unchanged and smooth. Critically, these nanoscale features would have been difficult, if not impossible, to identify using traditional optical profilometry methods. Following cell plating, AFM clearly shows protruding cells on the control surface and a “planarizing” of the nanoscopically rough surfaces of instrumented Ti and Ti‐Zr. This likely occurs by filling of the pits and fissures with extracellular matrix during cell attachment. Alternatively, on ZrO2, the cells protruded from the surface for both the control and instrumented surface. In conclusion, the increase in nanoscale roughness following instrumentation, along with macroscale roughness, may play a significant role in HGF attachment and adhesion for dental implant and healing abutment materials, as it is more consistent with cellular size scales.Support or Funding InformationThis research was partially supported by a research grant from Straumann USA (IIS 15‐12).
Premature ovarian failure patient‐specific induced pluripotent stem (iPS) cells show compromised potential to develop to germ cells and granulosa cells
Authors: Lu Chen‐Yu , Chen Yu‐An , Wu Fang‐Chun , Chang Nan‐Shan , Ho Hong‐Nerng , Chen Hsin‐Fu 
Published: November 2023

Premature ovarian failure (POF), also called primary ovarian insufficiency (POI), is a common endocrine disorder in females, accounting for 1–2% in women during the reproductive ages. Patients with the disease experience spontaneous menopause before the age of 40 years, and frequently encounter significant difficulties and pains in overcoming the problems of infertility and menopausal syndrome. However, the mechanisms underlying POF are difficult to study due to the lack of a suitable disease model. Recently pluripotent stem cells, including human embryonic stem (ES) cells and human induced pluripotent stem (iPS) cells, are becoming useful cell sources to study and dissect the molecular mechanisms underlying in vitro differentiation into specialized cell types. We and other researchers have previously shown that pluripotent stem cells including human ES cells and iPS cells are capable of developing into germ cells and granulosa cells. In this study, we derived POF patient‐specific iPS cell lines from three patients and two controls using skin fibroblasts or PBMCs and induced them to early female germ cells expressing germ cell markers VASA and GDF9 and meiosis marker SCP3, and also to granulosa‐like cells expressing FOXL2, FSHR, AMHR2, AMH and CYP19A1 (aromatase). We observed that the differentiated POF‐patient iPS cells showed differential expression levels of the granulosa cell markers and VASA, when compared to NTU1 human embryonic stem cells. The data demonstrated that iPS cells can be produced from POF patients and control subjects, and these cells can be induced in vitro to early germ cells and granulosa cells, but significantly with compromised potential when compared to other pluripotent stem cells. The POF patient‐specific iPS cells derived in this study thus represent a very useful disease model for further studies to test the disease mechanisms and to test drugs that may be useful for treating POF.Support or Funding InformationNational Science Council of the Republic of China (NSC) and National Taiwan University Hospital (NTUH), Taiwan
Functional cranial joint histology in Anas platyrhynchos: a window to understand avian cranial kinesis
Authors: Bailleul Alida M , Holliday Casey M 
Published: November 2023

Many of the cranial joints of birds allow significant cranial kinesis, a phenomenon in part responsible for the remarkable diversity of avian feeding adaptations. Whereas some morphological and biomechanical features of cranial kinesis have been studied, little is known about joint structure at the microscopic scale. Consequently, it is still unclear: 1) how the skeletal tissues found at these joints mediate intracranial movements; 2) how these cranial joints vary among different reptile clades; and 3) if specific tissues coincide with particular loading environments. These data are key to understanding the structural basis of kinesis, how secondary articulations form and the origins of the avian feeding apparatus.Here we investigated the functional joint histology of the duck (Anas platyrhynchos). Ducks have derived adaptations for herbivory and are model organisms in developmental biology and biomechanics. A total of five specimens (three adults and two hatchlings) were histologically sampled. Two other specimens were CT‐scanned using contrast‐enhancing techniques to build 3D anatomical and biomechanical models. Five intracranial joints were sampled: three diarthroses (jaw joint, otic joint and palatobasal joint) and two syndesmoses (mandibular symphysis and craniofacial hinge). CT data were registered with histological slides to better compare 3D structure.The jaw, otic and palatobasal joints are all synovial, with a synovial cavity encasing cartilage on each articular surface. The prokinetic hinge is a complex joint: laterally it is synovial, whereas medially it is a synostosis. The mandibular symphysis is a synostosis. Upon comparisons with functionally homologous, albeit structurally analogous joints in lizards and crocodylians, major differences in tissue organization occur within the otic and palatobasal joints, as well as in portions of the craniofacial hinge, likely reflecting each clade's developmental and phylogenetic trajectories. These clade‐specific differences in joint microstructure are possibly responsible for the wide range of skull morphologies and cranial kinesis in reptiles. The results of this study have significant implications to understanding the origins of avian cranial kinesis in a broader phylogenetic context (i.e., within non‐avian dinosaurs).Support or Funding InformationThis study was funded by: NSF‐IOS 1457319; Department of Pathology and Anatomical Sciences.
Evolvability and the Diversification of the Craniofacial Skeleton in the Domesticated Pigeon (Columba livia)
Authors: Linde‐Medina Marta , Fondon John , Marcucio Ralph , Hallgrímsson Benedikt , Young Nathan M. 
Published: November 2023

The elucidation of the mechanisms underlying the evolution of complex structures, like the cranium, represents a principal aim in evolutionary biology. It has been argued that the evolution of a modular organization, by which different subunits of a structure can change relatively independent from one another, has favored the morphological diversification of complex structures. However, the potential of species to diversify can be hidden in natural populations due to the fact that both natural selection and genetic drift tend to reduce phenotypic variation. This mismatch between potential and actual phenotypic variation will confound studies aimed to understand the role of integration and modularity in the evolution of complex structures. For example, a taxon with a high degree of modularity could display lower phenotypic variation than a taxon with low modularity if the former evolved under strong stabilizing selection. Domesticated species are characterized for displaying a wider spectrum of morphologies than their wild populations. Thus, domesticated species offer a unique opportunity to investigate if this increase in phenotypic diversification is related to changes in pattern and/or magnitude of morphological integration and modularity or, instead, it reflects the potential of a common structural pattern to generate phenotypic variation, i.e. the evolvability of the wild population. Here we use geometric morphometrics to quantify variation in cranium size and shape of domesticated pigeons and compare this to their feral counterparts. We show that domesticated pigeons do not represent novel phenotypes but extensions of variation already present in the feral population. We also show that the increase of variation in domesticated pigeons would mainly reflect the evolvability of the feral population.Support or Funding InformationNational Institutes of Health Grants R01DE019638 and R01DE021708.
The Effects of Body Weight Supported Physical Activity on Joint Pain, Function and Thigh Muscle Strength in Overweight Patients with Mild – Moderate Knee Osteoarthritis
Authors: Peeler Jason , Leiter Jeffrey , MacDonald Peter 
Published: November 2023

PurposeTo examine the effect of a 12‐week lower body positive pressure (LBPP) supported low‐load treadmill walking program on knee joint pain, function, and thigh muscle strength in overweight knee OA patients.DesignProspective, observational, repeated measures.SettingCommunity based, multidisciplinary sports medicine clinic.ParticipantsThirty‐one patients between the ages of 55–75, with a body mass index (BMI) ≥ 25 kg/m2 and mild to moderate knee OA.InterventionParticipants exercised under low‐load treadmill walking conditions twice weekly (for 12 weeks) using an amount of lower body positive pressure (LBPP) support that minimized knee pain while walking for a period of 25 minutes at a set speed of 3.1 mph at 0° incline.Main Outcome MeasurementsAcute knee pain (VAS) during full weight bearing treadmill walking, chronic knee pain and joint function (KOOS questionnaire) during normal activities of daily living, thigh muscle strength (Biodex isokentic dynamometer), and body anthropometry were assessed at baseline, week 13, and again at week 46.ResultsImmediately following completion of the 12 week exercise regimen, participants reported significant improvements in chronic knee pain and function, and demonstrated significant increases in thigh muscle strength about the degenerative knee. Participants also experienced significant reductions in acute knee pain during full‐weight bearing treadmill walking, and required dramatically less LBPP support in order to walk pain free on the treadmill. More than 33 weeks following exercise cessation, patients continued to report improvements in knee joint pain and symptoms; experienced enhanced joint function; and maintained thigh muscle strength gains.ConclusionsData suggest that a LBPP supported low‐load exercise regime can be used to significantly diminish knee pain, enhance joint function and increase thigh muscle strength, while safely promoting pain‐free walking exercise in over‐weight knee OA patients. These findings have important implications for the development and refinement of exercise strategies and interventions used in the management of joint symptoms associated with knee OA, and for improving the physical health, quality of life and social well‐being of North America's aging population.Impact of the StudyLower body positive pressure (LBPP) supported low‐load exercise is a safe user‐friendly mode of exercise that can be successfully used in the management of day‐to‐day joint symptoms associated with knee osteoarthritis, as well as to study the long term impact of regular exercise on knee OA pathogeneses and progression.Support or Funding InformationFunding provided by the Manitoba Centre on Aging, and on‐going support through the University of Manitoba and the Pan Am Clinic Foundation.
The Collaborative Undergraduate Research Lab: Using Yeast Genetics To Create An Authentic Research Experience For Freshman
Authors: Johnson Tracy 
Published: November 2023

In the last several years, there has been a growing recognition of the value of discovery‐driven research experiences for undergraduates. The benefits are well‐documented, including better learning outcomes, higher overall GPAs, and increased persistence in STEM disciplines. Notably, while the data are compelling for students in general, there appear to be particularly strong benefits for students who come from historically underrepresented backgrounds. A key component of persistence in STEM, particularly for traditionally underrepresented students, is their ability to identify as scientists (See for example Estrada‐Hollenbeck et al. J. Educ. Psychology 2011). To this end, and with the support of the Howard Hughes Medical Institute (HHMI) Professors program, we have developed the Collaborative Undergraduate Research Lab (CURL) to provide first year students with a discovery‐based, authentic research experience within a classroom setting.The CURL is an introductory course that provides research training for up to 22 students in a 10‐week quarter and includes complementary instruction in genetics, molecular biology, and bioinformatics. Additionally, the course includes intensive focus on laboratory ethics, science writing (grants and manuscripts), and research presentation—all of which are key components of research science. The CURL is closely aligned with my laboratory's research, which focuses on understanding the process of RNA splicing. The students in the CURL address the basic question: How does the cellular machinery that carries out RNA splicing (the spliceosome) work? Using the genetically tractable model organism Saccharomyces cerevisiae (budding yeast) the students perform a genetic screen to generate mutants that they then characterize using molecular genetics approaches. At the end of the quarter, when the mutants have been identified and characterized, the students present their research findings to each other and to a panel of faculty observers and prepare their contributions for a publication that includes all of the students as co‐authors, which is currently in preparation.Our initial assessment indicates that engaging early‐stage students in inquiry based research experiences that mirror the activities of professional research scientists can have a profound effect on student learning outcomes, identification as scientists, and the propensity to pursue research opportunities in STEM disciplines. The results of these assessments will be presented here.Support or Funding InformationHoward Hughes Medical Institute (HHMI) Award# 52008140
Laterality and Locality of Metastatic Renal Cell Carcinoma to Pancreatic Position; Right Kidney RCC Mechanism of Dissemination to Pancreatic Position
Authors: Hartley Christopher Kirk , Raffoul Adam , Johnson Marjorie , Gomez Jose A , Pautler Stephen , McAlister Vivian 
Published: November 2023

IntroductionRenal cell carcinoma (RCC) accounts for approximately 3% of all adult malignancies. Although RCC does not commonly metastasize to the pancreas, it is the most common source of metastasis in the pancreas. RCC preferentially disseminates via the renal vein to common sites such as the lung, brain, and bone. Current literature does not document a physical explanation for why the pancreas is susceptible to RCC metastasis as it is upstream in the venous drainage. We hypothesize a potential undocumented local vascular or lymphatic route from the kidney to the pancreas to explain pancreatic susceptibility to RCCs. This study aims to map anatomical structures and pathways that might be responsible for metastatic spread between the right perinephric compartment and anterior paranephric compartment.MethodsFour fresh frozen cadaveric specimens and 20 fixed cadaveric specimens are in the process of microdissection following vascular latex injection.A study is underway to map perinephric and anterior paranephric lymphatics and lymph nodes will be identified using GEWF (glacial acetic acid, ethanol, distilled water, and formaldehyde) and immunohistochemistry for monoclonal antibody D2–40 (a marker of lymphatic endothelium). Vasculature will be identified under a dissection microscope and further characterized using immunohistochemistry for polyclonal antibody CD31 (a pan‐endothelial marker).Preliminary resultsVasculature has been observed exiting the kidney via the capsule into the perinephric fat. Microdissection has revealed a rich vessel network supplying the superior medial aspect of the perirenal space converging on the adrenal gland. In addition, vasculature has been observed extending to and running along the internal barrier of Gerota's fascia. The GEWF solution is being tested on axillary fat as a control for comparison of lymph node identification in the renal perinephric and paranephric fat.DiscussionAnatomical understanding of the vascular and lymphatic pathways between the kidney and the pancreas will help determine the extent of radical resection surgery with a curative intent. In addition, our study may have implications on the local resection of tumors.
a Medium‐sized, Enlarged Anatomical Model of Human Ear in plaster (first middle of the 20th century)
Authors: LE FLOCH‐PRIGENT PATRICE P , FROMAGER VALERIE , GILLOT JEAN‐BERNARD 
Published: November 2023

An enlarged model of the human ear represented the temporal bone with the elements of the middle ear. It was 30 cm long, 22 cm wide and 14 cm high. The basis (26,7 ; 16,3 ; 2,5 cm) was in wood painted in black. The osseous sections of the temporal bone (squamous part and roof of the petrous bone) were represented with the diploë. The tympanic membrane presented a 5 mm peripheral annulus and was 5 cm wide and 5,5 cm high. The malleus, uncus and corda tympani (VII) were stuck on the medial face of the tympanic membrane. The internal carotid artery was represented in its extra and intra‐cranial aspect. The internal jugular vein was represented in its extra‐cranial aspect. The elements of the internal ear were missing. Numerous numbers and letters corresponded to legends of which the text was unknown. The roof of the petrous bone was missing. A well drawn auricle was present. This sample in plaster was very similar to a still greater one belonging also to the Scientific Library Brieux ‐ Gillot in Paris (France) on january 2015. Their craftsman was identical.Support or Funding InformationLibrairie scientifique Brieux ‐ Gillot, 48 rue Jacob, 75006 Paris ‐ France