bluuebunny/crossref_metadata_2025_split huggingface dataset:
μCT ANALYSIS AND 3D MODELLING OF COMPARATIVE FLUID PERMEABILITY OF HUMAN TALI FOLLOWING THREE DIFFERENT CLINICAL PROCEDURES: NANOFRACTURE, MICROFRACTURE, AND FINE WIRE DRILLING
Authors: Warren James , Canden Ahranee , Farndon Mark , Brockett Claire 
Published: November 2023

AbstractObjectivesThe aim of this work was to compare the different techniques and the different fluid permeability of the tissue following each technique through assessing the flow of radiopaque contrast agent using μCT image analysis and 3D modelling.MethodsDonated human tali specimens (n=12) were prepared through creating a 10mm diameter chondral defect in three different regions of each talus. Each region then underwent one of three surgical techniques: 1) Fine wire drilling, 2) Nanofracture or 3) Microfracture, equidistant sites in each defect to ensure even distribution. Each region then had an addition of 0.1 ml radiopaque contrast agent (Omnipaque™ 300), imaged using a clinical μCT scanner (SCANCO Medical AG, 73.6 μm resolution). Each μCT scan was segmented using Slicer 3D software (The Slicer Community, 2023 3D Slicer (5.2.2)). The segmentation package was used to segment the bone and contrast agent regions in each different surgical site of each sample. Each defect site was created into a cylinder and the ratio of segmented pixels of contrast agent against bone.ResultsThe μCT analysis indicated that across the 12 samples, eight nanofracture regions demonstrated flow of the contrast agent either to the depth of the fracture site or deeper. Some lateral flow was also observed in these sites. eight microfracture regions demonstrated that the flow of the contrast agent was localised to the fracture site and a preferential flow laterally. In only one sample, did a fine wire drilling region demonstrate any fluid flow. In this sample, contrast agent had permeated through the drilling site to the bottom and some sub-site permeation was observed. However, in all samples that showed no permeation of contrast agent through the fracture site, a layer of contrast agent on the chondral surface or minor permeation through to the sub-chondral surface. Segmentation of each sample site showed a significant increase (n=12, p<0.05) in fluid flow of the contrast agent in the nanofracture sites (11%) compared to microfracture (5%) and fine wire drilling (2%).ConclusionsNanofracture showed significantly improved fluid permeability throughout the surrounding trabecular structure, when compared to microfracture and fine wire drilling. Microfracture appears to allow some fluid flow, but only confined to the immediate area around the fracture site, while fine wire drilling appears to allow a comparably small amount, if not no fluid flow through the surrounding trabecular tissue. This conclusion is reinforced by previous literature that concluded the damage to the structure of the trabecular tissue is reduced when using nanofracture, compared to the other two techniques.Declaration of Interest(a) fully declare any financial or other potential conflict of interest
EVALUATING THE UTILITY OF SPECT/CT FOR THE IDENTIFICATION OF CARTILAGE LESIONS: A SYSTEMATIC REVIEW
Authors: Rix Larissa , Tushingham Samuel , Wright Karina , Snow Martyn 
Published: November 2023

AbstractObjectiveA common orthopaedic pain found in a wide spectrum of individuals, from young and active to the elderly is anterior knee pain (AKP). It is a multifactorial disorder which is thought to occur through muscular imbalance, overuse, trauma, and structural malalignment. Over time, this can result in cartilage damage and subsequent chondral lesions. Whilst the current gold standard for chondral lesion detection is MRI, it is not a highly sensitive tool, with around 20% of lesions thought to be mis-diagnosed by MRI. Single-photon emission computerised tomography with conventional computer tomography (SPECT/CT) is an emerging technology, which may hold clinical value for the detection of chondral lesions. SPECT/CT may provide valuable diagnostic information for AKP patients who demonstrate absence of structural change on other imaging modalities. This review systematically assessed the value of SPECT/CT as an imaging modality for knee pain, and its ability to diagnose chondral lesions for patients who present with knee pain.MethodsUsing PRISMA guidelines, a systematic search was carried out in PubMed, Science Direct, and Web of Knowledge, CINAHL, AMED, Ovid Emcare and Embase. Inclusion criteria consisted of any English language article focusing on the diagnostic value of SPECT/CT for knee chondral lesions and knee pain. Furthermore, animal or cadaver studies, comparator technique other than SPECT/CT or patients with a pathology other than knee chondral lesions were excluded from the study. Relevant articles underwent QUADAS-2 bias assessment.Results11,982 manuscripts were identified, and the titles were screened for relevance. Seven studies were selected as being appropriate and were subjected to QUADAS-2 assessment. All 7 articles scored low for bias. Two papers deemed that the ICRS score of chondral lesions at intraoperative assessment correlated with SPECT/CT tracer uptake. Two studies concluded that MRI significantly correlated with SPECT/CT tracer uptake, with some instances whereby SPECT/CT identified more chondral lesions than MRI. Two papers compared bone scintigraphy (BS) to SPECT/CT and concluded that SPECT/CT was not only able to identify more chondral lesions than BS, but also localise and characterise the lesions.ConclusionEvidence implies that SPECT/CT may be a useful imaging modality for the detection and localisation of cartilage lesions, particularly in discrepant cases whereby there is an absence of lesions on other imaging modalities, or a lack of correspondence with patients’ symptoms. More studies would be of value to confirm the conclusions of this review.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
SYNOVIAL FLUID PROTEOMICS AND BIOINFORMATICS HIGHLIGHTS POTENTIAL MECHANISMS OF UMBILICAL CORD-MSC INDUCED RADIOLOGICAL IMPROVEMENT IN AN OVINE MODEL OF OSTEOARTHRITIS
Authors: Wright Karina , McDonald Jamie , Mennan Claire , Perry Jade , Peffers Mandy , Hulme Charlotte 
Published: November 2023

AbstractObjectivesA promising therapy for early osteoarthritis (OA) is the transplantation of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs). The synovial fluid (SF) from a pre-clinical ovine model treated with hUC-MSCs has been profiled using proteomics and bioinformatics to elucidate potential mechanisms of therapeutic effect.MethodsFour weeks after a medial meniscus transection surgery, sheep were injected with 107 hUC-MSCs in Phosphate Buffered Saline (PBS) or PBS only (n=7) and sacrificed at 12 weeks. SF was normalised for protein abundance (ProteoMinerTM) and analysed using label-free quantitation proteomics. Bioinformatics analyses (Ingenuity Pathway Analysis (IPA) and STRING) were used to assess differentially regulated functions from the proteomic data. Human orthologues were identified for the ovine proteins using UniProt and DAVID resources and proteins that were ≥±1.3 fold differentially abundant between treatment groups, were included in the bioinformatics analyses.ResultshUC-MSC treated animals demonstrated significantly less joint space narrowing. Nineteen SF proteins were differentially abundant in treated cf. control sheep (FC±2.0; p<0.05). Biglycan (a small leucine-rich proteoglycan of the cartilage extracellular matrix) abundance was increased by 2.1 fold in treated compared to untreated sheep (p=0.024). IPA indicated that lipid synthesis (z-score=1.772; p=0.00267) and immune cell migration pathways (cell movement of mononuclear leukocytes: z-score=1.761; p=0.00259), amongst others, were likely to be activated in the treated sheep. Conversely, tissue damage (z-score=−2; p=0.00019), senescence (z-score=−1.981; p=0.00007) and necrosis (z-score=−1.728; p=0.00829) associated pathways as well as inflammation (z-score=−1.718; p=0.00057) and vascular permeability (z-score=−1.698; p=0.00002) were likely to be inhibited in treated cf. untreated sheep.ConclusionshUC-MSC treatment prevented/delayed OA progression, demonstrated via a reduction in joint space narrowing. SF proteome bioinformatics revealed potential mechanisms of therapeutic action related to immunomodulation and the inhibition of multiple cell death, and tissue damage associated pathways. Further, a potential predicted upregulation in lipid synthesis in treated sheep represents a novel mechanism warranting further investigation. Additional work is required to validate these discovery phase proteomic findings in studies which specifically target and manipulate the proposed mechanisms highlighted.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
PATIENT-SPECIFIC DISTAL FEMORAL OSTEOTOMY REDUCES SURGICAL TIME: DEMONSTRATION OF A NOVEL PATIENT-SPECIFIC TECHNIQUE
Authors: Bishop Mathew , Zaffagnini Stefano , Grassi Alberto , Fabbro Giacomo Dal , Smyrl Graeme , Roberts Samuel , MacLeod Alisdair 
Published: November 2023

AbstractBackgroundDistal femoral osteotomy is an established successful procedure which can delay the progression of arthritis and the need for knee arthroplasty. The surgery, however, is complex and lengthy and consequently it is generally the preserve of highly experienced specialists and thus not widely offered. Patient specific instrumentation is known to reduce procedural complexity, time, and surgeons’ anxiety levels1 in proximal tibial osteotomy procedures. This study evaluated a novel patient specific distal femoral osteotomy procedure (Orthoscape, Bath, UK) which aimed to use custom-made implants and instrumentation to provide a precision correction while also simplifying the procedure so that more surgeons would be comfortable offering the procedure.Presenting problemThree patients (n=3) with early-stage knee arthritis presented with valgus malalignment, the source of which was predominantly located within the distal femur, rather than intraarticular. Using conventional techniques and instrumentation, distal femoral knee osteotomy cases typically require 1.5–2 hours surgery time. The use of bi-planar osteotomy cuts have been shown to improve intraoperative stability as well as bone healing times2. This normally also increases surgical complexity; however, multiple cutting slots can be easily incorporated into patient specific instrumentation.Clinical managementAll three cases were treated at a high-volume tertiary referral centre (Istituto Ortopedico Rizzoli, Bologna) using medial closing wedge distal femoral knee osteotomies by a team experienced in using patient specific osteotomy systems3. Virtual surgical planning was conducted using CT-scans and long-leg weight-bearing x-rays (Orthoscape, Bath, UK). Patient specific surgical guides and custom-made locking plates were design for each case. The guides were designed to allow temporary positioning, drilling and bi-planar saw-cutting. The drills were positioned such that the drills above and below the osteotomy became parallel on closing following osteotomy wedge removal. This gave reassurance of the achieved correction allowed the plate to be located precisely over the drills. All screw lengths were pre-measured.DiscussionThe surgical time reduced to approximately 30 minutes by the third procedure. It was evident that surgical time was saved because no intraoperative screw length measurements were required, relatively few x-rays were used to confirm the position of the surgical guide, and the use of custom instrumentation significantly reduced the surgical inventory. The reduced invasiveness and ease of surgery may contribute to faster patient recovery compared to conventional techniques. The final post-operative alignment was within 1° of the planned alignment in all cases.Declaration of Interest(a) fully declare any financial or other potential conflict of interest
HUMAN MONOCYTES AND MESENCHYMAL STEM/STROMAL CELLS CO-CULTURED IN FIBRIN HAVE A PRO-REPAIR PHENOTYPE THAT INFLUENCES CHONDROCYTE ACTIVITY
Authors: Alkhrayef Mohammad , Muhammad Hayat , Hosni Rawiya Al , McCaskie Andrew , Birch Mark 
Published: November 2023

AbstractObjectivesTissue repair is believed to rely on tissue-resident progenitor cell populations proliferating, migrating, and undergoing differentiation at the site of injury. During these processes, the crosstalk between mesenchymal stromal/stem cells (MSCs) and macrophages has been shown to play a pivotal role. However, the influence of extracellular matrix (ECM) remodelling in this crosstalk, remains elusive.MethodsHuman MSCs cultured on tissue culture plastic (TCP) and encased within fibrin in vitro were treated with/without TNFα and IFNγ. Human monocytes were cocultured with untreated/pretreated MSCs on TCP or within fibrin. After seven days, the conditioned media (CM) were collected. Human chondrocytes were exposed to CM in a migration assay. The impact of TGFβ was assessed by adding an inhibitor (TGFβRi). Cell activity was assessed using RT-qPCR and XL-protein-profiler-array.ResultsPreviously, we demonstrated that culturing human MSCs within 3D-environments significantly enhances their immunoregulatory activity in response to pro-inflammatory stimuli. In this study, monocytes were co-cultured with MSCs within fibrin, acquiring a distinct M2-like repair macrophage phenotype in contrast to TCP co-cultures. MSC/macrophage CM characterization using a protein array demonstrated differences in release of several factors, including chemokines, growth factors and ECM components. Chondrocyte migration was significantly reduced in CM from untreated MSC/monocytes co-cultures in fibrin compared to CM of untreated MSCs/monocytes on TCP. This impact on migration was not seen with chondrocytes cultured in CM of monocytes co-cultured with pretreated MSCs in fibrin. The CM of monocytes co-cultured with pretreated MSCs in fibrin up-regulates COL2A1 and SOX9 compared to TCP. Chondrogenesis and migration were TGFβ dependent.ConclusionMSC/macrophage crosstalk and responsiveness to cytokines are influenced by the ECM environment, which subsequently impacts tissue-resident cell migration and chondrogenesis. The direct effects of ECM on MSC/macrophage secretory phenotype is complemented by the dynamic ECM binding and release of growth factors such as TGFβ.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
SENESCENCE OR APOPTOSIS: CHONDROCYTE RESPONSE TO INFLAMMATION IN VITRO IS DEPENDENT ON ITS DIMENSIONAL ENVIRONMENT
Authors: Strangmark Estelle , Wang Jia Hua , Hosni Rawiya Al , Muhammad Hayat , Alkhrayef Mohammad , Robertson-Waters Eve , MacMillan Alexandra , Gompels Benjamin , Vogt Antonia , Khan Wasim , Birch Mark , McCaskie Andrew 
Published: November 2023

AbstractBACKGROUNDCell culture on tissue culture plastic (TCP) is widely used across biomedical research to understand the in vivo environment of a targeted biological system. However, growing evidence indicates that the characteristics of cells investigated in this way differ substantially from their characteristics in the human body. The limitations of TCP monolayer cell cultures are especially relevant for chondrocytes, the cell population responsible for producing cartilage matrix, because their zonal organization in hyaline cartilage is not preserved in a flattened monolayer assay.OBJECTIVEHere, we contrast the response of primary human chondrocytes to inflammatory cytokines, tumor necrosis factor-alpha and interferon-gamma, via transcriptional, translational, and histological profiling, when grown either on TCP or within a 3D cell pellet (scaffold-less). We focus on anti-apoptotic (Bcl2), pro-apoptotic (Bax, Mff, Fis1), and senescent (MMP13, MMP1, PCNA, p16, p21) markers.RESULTSWe find that the 3D environment of the chondrocyte has a profound effect on the behavior and fate of the cell; in TCP monolayer cultures, chondrocytes become anti-apoptotic and undergo senescence in response to inflammatory cytokines, whereas in 3D cell pellet cultures, they exhibit a pro-apoptotic response.CONCLUSIONOur findings demonstrate that chondrocyte culture environment plays a pivotal role in cell behavior, which has important implications for the clinical applicability of in vitro research of cartilage repair. Although there are practical advantages to 2D cell cultures, our data suggest researchers should be cautious when drawing conclusions if they intend to extrapolate findings to in vivo phenomena. Our data demonstrates opposing chondrocyte responses in relation to apoptosis and senescence, which appear to be solely reliant on the environment of the culture system. This biological observation highlights that proper experimental design is crucial to increase the clinical utility of cartilage repair experiments and streamline their translation to therapy development.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
CLINICAL VALUE OF ELECTIVE POSTOPERATIVE RADIOGRAPHS IN TOTAL JOINT REPLACEMENT
Authors: Rajab Ali , Ponsworno Kimberly , Keehan Robert , Ahmad Riaz 
Published: November 2023

AbstractBackgroundPost operative radiographs following total joint arthroplasty are requested as part of routine follow up in many institutions. These studies have a significant cost to the local departments, in terms of financial and clinic resources, however, previous research has suggested they may not alter the course of the patients treatment. The purpose of this study was to assess the significance of elective post operative radiographs on changes in management of patients who underwent total joint arthroplasty.MethodAll patients who underwent total knee arthroplasty and total hip arthroplasty at a District General Hospital from 2019 to 2020 were included. Data was collected retrospectively from medical records and radiograph requests. Alterations to clinical management based on radiographic findings were reviewed in clinic letters.ResultsA total of 227 Total joint arthroplasty were retrieved. With 111(49%) total hip arthroplasty and 116 (51%) total knee arthroplasty. 54 were excluded due to having no clinical follow up and 173 met inclusion criteria. 56 (32%) had their post operative elective radiograph, while 93 (53.8%) patients had none. There were no abnormalities detected from the elective radiographs and none of the patients returned to the theatre. 24 patients (13%) presented with symptoms and had non-elective radiographs, 16 (67%) did not have any interventions and 8 (4.6%) required intervention and were taken to theatre. Discussion: Not performing these radiographs saves time, cost, and prevents unnecessary radiation exposure. In our institution, a 2-view joint radiograph costs £29 and takes roughly 15 minutes. This does not include indirect costs of additional clinic time and patient waiting time. In the larger context, the cost associated with elective radiographs is significant and our data suggests that routine post-operative radiographs are not beneficial as part of standard post-operative protocol for asymptomatic patients. However, performing imaging remains beneficial for patients who re-present with symptoms.ConclusionRoutine elective post-operative joint radiographs did not detect any true abnormalities. Information from elective radiographs has no clinical significance and did not change management. Therefore, this study recommends that there is no rationale requesting elective post-operative joint radiographs.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Spectral precision improvement with demagnifying spectral images in spectroscopic nanoscopy
Authors: Song Ki-Hee , Zhang Yang 
Published: November 2023

Spectroscopic nanoscopy (SN) has been recognized as a key functional imaging tool in cell biology and chemistry because it offers the unique capability to simultaneously obtain the spatial and spectral information for single molecules. However, it has an intrinsic issue in using the limited photon budget from single emitters divided into two imaging channels to concurrently acquire spatial and spectral images. Accordingly, this issue lowers the spatial localization and spectral precision. Although several techniques have been introduced to improve the spatial precision in SN, improving the spectral precision has been overlooked so far. Here we propose a method to improve the spectral precision by optically manipulating the width of the spectroscopic signatures using a demagnifier. We evaluate its performance using numerical simulations with systematic investigations of several underlying optimal parameters such as the demagnification factor and the integration width in the proposed configuration. We also present achievable spectral precision values with different signal and background levels. Compared to the existing SN system, the 3× demagnifier-based configuration shows an approximate 35% improvement, from 2.9 nm to 1.9 nm, in the spectral precision at the 1000 photons signal level.
Vegetable oil-based surfactants are adjuvants that enhance the efficacy of neonicotinoid insecticides and can bias susceptibility testing in adult mosquitoes
Authors: Ashu Fred A. , Fouet Caroline , Ambadiang Marilene M. , Penlap-Beng Véronique , Kamdem Colince 
Published: November 2023

Background
The standard operating procedure for testing the susceptibility of adult mosquitoes to neonicotinoid or butenolide insecticides recommends using a vegetable oil ester (Mero) as a surfactant. However, there is growing evidence that this adjuvant contains surfactants that can enhance insecticide activity, mask resistance and bias the bioassay.

Methodology/Principal findings
Using standard bioassays, we tested the effects of commercial formulations of vegetable oil-based surfactants similar to Mero on the activity of a spectrum of active ingredients including four neonicotinoids (acetamiprid, clothianidin, imidacloprid and thiamethoxam) and two pyrethroids (permethrin and deltamethrin). We found that three different brands of linseed oil soap used as cleaning products drastically enhanced neonicotinoid activity in Anopheles mosquitoes. At 1% (v/v), the surfactant reduced the median lethal concentration, LC50, of clothianidin more than 10-fold both in susceptible and in resistant populations of Anopheles gambiae. At 1% or 0.5% (v/v), linseed oil soap restored the susceptibility of adult mosquitoes fully to clothianidin, thiamethoxam and imidacloprid and partially to acetamiprid. By contrast, adding soap to the active ingredient did not significantly affect the level of resistance to permethrin or deltamethrin suggesting that vegetable oil-based surfactants specifically enhance the potency of some classes of insecticides.

Conclusions/Significance
Our findings indicate that surfactants are not inert ingredients, and their use in susceptibility testing may jeopardize the ability to detect resistance. Further research is needed to evaluate the potential, the limitations and the challenges of using some surfactants as adjuvants to enhance the potency of some chemicals applied in mosquito control.