bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANISOTROPIC COLLAGEN/HYALURONAN 3D-PRINTED HYDROGELS AS NOVEL IN VITRO MODEL OF ANNULUS FIBROSUS
Authors: Oliveira S. D. , Miklosic G. , Guicheux J. , Visage C. L. , D'este M. , Helary C. 
Published: November 2024

INTRODUCTIONIntervertebral disc (IVD) degeneration is not completely understood because of the lack of relevant models. In vivo models are inappropriate because animals are quadrupeds. IVD is composed of the Nucleus Pulposus (NP) and the Annulus Fibrosus (AF), an elastic tissue that surrounds NP. AF consists of concentric lamellae made of collagen I and glycosaminoglycans with fibroblast-like cells located between layers. In this study, we aimed to develop a novel 3D in vitro model of Annulus Fibrosus to study its degeneration. For this purpose, we reproduced the microenvironment of AF cells using 3D printing.METHODAn ink consisting of dense collagen (30 mg.mL-1) and tyramine-functionalized hyaluronic acid (THA) at 7.5 mg.mL-1 was first designed by modulating pH and [NaCl] in order to inhibit the formation of polyionic complexes between collagen and THA. Then, composite inks were printed in different gelling baths to form collagen hydrogels. Last, THA photocrosslinking using eosin and green light was performed to strengthen hydrogels. Selected 3D printed constructs were then cellularized with fibroblasts.RESULTSThe physicochemical study revealed that collagen/THA solutions (4:1 ratio) used at pH 5 with 200 mM NaCl were homogenous. In addition, collagen fibrils were observed in these solutions. The dense composite collagen/THA inks printed in a 2X PBS bath rapidly gelled and the photo-crosslinking increased the mechanical properties by 2 to reach 25 kPa (Young's modulus). Then, 3D printing parameters were optimized (85 kPa, extrusion, 4.5 mm/s speed and 80% fill-in percentage) to generate flat and anisotropic lamellae observed by polarized light microscopy. For the in vitro study, several anisotropic layers were printed and fibroblasts seeded between them. Cells adhered to layers, spread, proliferate and aligned along the axis of printed layers.CONCLUSIONTaken together, these results show it is possible to reproduce in vitro the main AF's biochemical and physical properties.
IMPACT OF ANNULUS FIBROSUS STIFFNESS ON THE FRACTURE LOAD OF FUNCTIONAL SPINE UNITS
Authors: Strack D. , Mesbah M. , Rayudu N. M. , Baum T. , Kirschke J. , Subburaj K. 
Published: November 2024

IntroductionFunctional Spine Units (FSUs) play a vital role in understanding biomechanical characteristics of the spine, particularly bone fracture risk assessment. While established models focus on simulating axial compression of individual bones to assess fracture load, recent models underscore the importance of understanding fracture load within FSUs, offering a better representation of physiological conditions. Despite the limited number of FSU fracture studies, they predominantly rely on a linear material model with an annulus fibrosus Young's modulus set at 500 MPa, significantly higher than stiffness values (ca. 4 MPa) utilized in other FSU and spine section biomechanical models. Thus, this study aims to study the effect of varying annulus fibrosus stiffness on FSU fracture load, aiming to identify physiologically relevant biomechanical parameters.MethodSubject-specific geometry and material properties of bones were derived from computed tomography (CT) image data of five human cadaveric FSU specimens. The annulus fibrosus and nucleus pulposus were manually recreated and assigned linear elastic material properties. By subjecting the model to axial compression, the fracture load of the FSU was deduced from the peak of the force-displacement graph. To explore the effect of stiffness of the annulus fibrosus on simulated fracture load, we conducted a parameter study, varying stiffness values from the high 500 MPa to a more physiologically relevant 25 MPa, aiming to approximate values applied in FSU kinematic models while achieving bone fracture.ResultSignificant reductions in fracture load were observed, ranging from 23% to 46%, as annulus stiffness decreased from 500MPa to 25MPa. Additionally, a discernible, gradual decline in fracture load was observed with a decrease in stiffness values.ConclusionThe stiffness of the annulus fibrosus significantly influences the simulated fracture load of an FSU. Future investigations should prioritize biomechanically accurate modeling of the intervertebral disc, ensuring alignment with experimental findings regarding FSU fracture load while maintaining biomechanical fidelity.
POLYACRYLAMIDE HYDROGEL FOR KNEE OSTEOARTHRITIS: FOUR-YEAR RESULTS FROM A PROSPECTIVE STUDY
Authors: Bliddal H. , Beier J. , Hartkopp A. , Conaghan P. , Henriksen M. 
Published: November 2024

IntroductionPolyacrylamide hydrogel (iPAAG1), is CE marked for treating symptomatic knee osteoarthritis (OA), meeting the need for an effective, long-lasting, and safe non-surgical option. This study evaluates the efficacy and safety of a single 6 ml intra-articular injection of iPAAG in participants with moderate to severe knee OA over a 5-year post-treatment period, presenting data from the 4-year follow up.MethodThis prospective multicentre study (3 sites in Denmark) involved 49 participants (31 females) with an average age of 70 (range 44 – 86 years). They received a single 6 mL iPAAG injection. All participants provided informed consent and re-consented to continue after 1 year. The study followed GCP principles and was approved by Danish health authorities and local Health Research Ethics committees. Twenty-seven participants completed the 4-year follow-up.The study evaluated WOMAC pain, stiffness, function, and Patient Global Assessment (PGA) of disease impact. Changes from baseline were analysed using a mixed model for repeated measurement (MMRM). Sensitivity analyses were applied on the extension data, where the MMRM analysis was repeated only including patients in the extension phase and an ANCOVA model was used, replacing missing values at 4-years with baseline values (BOCF).ResultsThe planned MMRM analysis (n=49) revealed a statistically significant decrease in WOMAC pain subscale scores (-22.0; 95%CI: -29.5; -14.4) from baseline to 4-years. Analysis of the extension phase (n=27) showed similar results (-21.8; 95%CI: -29.0; -14.6) compared to the initial analysis. Furthermore, BOCF analysis indicated a statistically significant reduction in WOMAC pain subscale scores from baseline (-13.0 units). Four new adverse events were reported between the 3-year and 4-year visits; none were related to treatment.ConclusionsThis study shows that single injections of 6 ml intra-articular iPAAG were well tolerated and continued to provide clinically important effectiveness at 4-years after treatment.AcknowledgementsThe study was sponsored by Contura International A/S.
COMPREHENSIVE EVALUATION OF MUSCULOSKELETAL SOFT TISSUES BY CONTRAST-ENHANCED MICROCT AND HISTOLOGY: PERSPECTIVE AND LIMITS
Authors: Marchiori G. , Zaffagnini S. , Cavazza L. , Fabbro G. D. , Grassi A. , Lopomo N. F. , Giavaresi G. , Maglio M. 
Published: November 2024

IntroductionHistology is still considered the gold standard method for the evaluation of soft tissues in the musculoskeletal field, thanks to the possibility of studying structures using different staining and high magnification microscopy. To overcome the intrinsic limits of this method, contrast enhanced microtomographic (CE- microCT) protocols are constantly evolving to allow 3D study of soft tissues. However, no standardized approaches are available, and many concerns exist about the alterations induced to the samples.MethodmicroCT/histology protocols were explored on human tendons and menisci. To enhance contrast tissues for microCT scanning 1) examethyldisilazane drying 2) 2% phosphotungstic acid (PTA) in alcoholic solution exposition and 3) 2% PTA in aqueous solution exposition were performed; to observe PTA contrast progression, three exposition and scanning times were selected. microCT images were compared to histological slices obtained from the same samples, after rehydration protocols, or from adjacent tissues portion, stained with Picrosirius red to highlight the peculiar collagenic structures.ResultExposition times influence PTA diffusion and tissue contrast; its specificity for collagenic structure allow a clearer contrast of the tissues. Histological processing on the same samples is possible: PTA removal requires careful washing in basic solution to reduce the hardening of the sample, while drying can be reverted applying inverse protocol. Comparison with microCT images is really accurate if histology is performed on the same sample, although all protocols induce tissue shrinkage with relative packing of collagen fibers.ConclusionThe contrast approaches tested proved effective in highlighting the structures of both tendons and menisci, but the structural effects induced by tissue shrinkage do not allow a completely real microCT visualization of native tissue. Histology can be the reference method to monitor the efficacy of the contrast methods and the alterations induced to define the possibility of improvement of the technique.AcknowledgementPR23-PAS-P4 “ADJOINT 2”- INAIL
COMPARATIVE BIOMECHANICAL ANALYSIS OF SUPERIOR CAPSULAR RECONSTRUCTION (SCR) AND LOWER TRAPEZIUS TRANSFER (LTT) IN TREATING MASSIVE ROTATOR CUFF TEARS
Authors: Mungalpara N. , Kim S. , Baker H. , Lee C. , Shakya A. , Chen K. , Athiviraham A. , Koh J. , Elhassan B. , Maassen N. H. , Amirouche F. 
Published: November 2024

IntroductionTreatment strategies for irreparable Massive Rotator Cuff Tears (MRCTs) are debatable, especially for younger, active patients. Superior Capsular Reconstruction (SCR) acts as a static stabilizer, while Lower Trapezius Transfer (LTT) serves as a dynamic stabilizer. This study compares the biomechanical effectiveness of SCR and LTT, hypothesizing that their combination will enhance shoulder kinematics.MethodsEight human shoulders from donors aged 55-75 (mean = 63.75 years), balanced for gender, averaging 219.5 lbs, were used. Rotator cuff and deltoid tendons were connected to force sensors through a pulley system, with the deltoid linked to a servohydraulic motor for dynamic force measurement.ResultsFrom intact to MRCT, deltoid force was reduced by 28% (p = 0.023). LTT increased deltoid force by 27.25 (p = 0.166). SCR decreased deltoid force by 34% (p = 0.208). Combining LTT with SCR increased deltoid force by 32.57% compared to SCR (p = 0.023) and decreased it by 13.6% compared to LTT alone (p = 0.017). Combined LTT and SCR reduced deltoid force by 20.9% from the control (p = 0.001). Subacromial contact pressure rose by 15% in MRCT over intact, but LTT decreased it by 7.6%, achieving nearly 50% correction. SCR increased subacromial space volume, raising pressure by 6.5%. The humeral head translation (HHT) increases with MRCT, reaching 3.33 mm (SD = 0.95) at 0 degrees, compared to 2.24 mm (SD = 0.78) in the intact. LTT and the combined LTT + SCR significantly reduce HHT, with combined LTT + SCR achieving HHT of 2.24 mm (SD = 0.63) at 0 degrees, comparable to the control.ConclusionNotable changes in deltoid force were observed. LTT outperformed the combined SCR and LTT in reducing deltoid force and subacromial peak pressure. Both SCR and LTT corrected HTT, with LTT being more effective. However, combining SCR and LTT optimally corrected HHT.
OPTIMIZING PATIENT-SPECIFIC BONE FINITE ELEMENT ANALYSIS: MESH CONVERGENCE AND MATERIAL GROUPING STRATEGIES
Authors: Strack D. , Rayudu N. M. , Kirschke J. , Baum T. , Subburaj K. 
Published: November 2024

IntroductionPatient-specific biomechanical modeling using Finite Element Analysis (FEA) is pivotal for understanding the structural health of bones, optimizing surgical procedures, assessing outcomes, and validating medical devices, aligning with guidance issued by standards and regulatory bodies. Accurate mapping of image-to-mesh-material is crucial given bone's heterogeneous composition. This study aims to rigorously assess mesh convergence and evaluate the sensitivity of material grouping strategies in quantifying bone strength.MethodSubject-specific geometry and nonlinear material properties were derived from computed tomography (CT) scan data of one cadaveric human vertebral body. Linear tetrahedral elements with varying edge lengths between 2mm and 0.9mm were then generated to study the mesh convergence. To compare the effectiveness of different grouping strategies, three approaches were used: Modulus Gaping (a user-defined absolute threshold of Young's modulus ranging from 500 MPa to 1 MPa), Percentual Thresholding (relative parameter thresholds ranging from 50% to 1%), and Adaptive clustering (unsupervised k-means-based clustering ranging from 10 to 200 clusters). Adaptive clustering enables a constant number of unique material properties in cross-specimen studies, improving the validity of results.ResultMesh convergence was evaluated via fracture load and reached at a 1mm mesh size across grouping strategies. All strategies exhibit minimal deviation (within 5%) from individually assigned material parameters, except Modulus Gaping, with a 500 MPa threshold (32% difference). Computational efficiency, measured by runtime, significantly improved with grouping strategies, reducing computational cost by 82 to 94% and unique material count by up to 99%.ConclusionDifferent grouping strategies offer comparable mesh convergence, highlighting their potential to reduce computational complexity while maintaining accuracy in the biomechanical modeling of bones and suggesting a more efficient approach than individual element materials. The higher efficiency of FEA may increase its applicability in clinical settings with limited computational resources. Further studies are needed to refine grouping parameters and assess their suitability across different subjects.
Compact cavity-enhanced aerosol detector using incoherent light sources
Authors: Williamson Jacob , Muthukrishnan Pranav Chamakkad , Nandanwar Srushti , Guo Shuaifeng , Raman Chandra 
Published: November 2024

We have realized a compact optical particle counter utilizing
enhancement of light scattering within a high finesse Fabry–Perot
optical cavity. In contrast with laser-based approaches such as cavity
ringdown spectroscopy, we use the light stream from superluminescent
and light-emitting diodes that have no longitudinal coherence. This
eliminates the vibration sensitivity that is
typical of laser-based cavity
methods. The use of the transmission mode of detection allows us to
reduce the cavity mirror separation to below 1 cm, with no
obvious limit to miniaturization. Typical light scattering instruments
are larger, in part due to their sensitivity to background signals
from the light source. Our approach paves the way toward what we
believe to be is a new generation of compact and portable instruments.
A simultaneous comparison of the scattering signals with a commercial
particle counter suggests that our cavity may be sensitive to
ultrafine particles below 300 nm diameter, which are typically
not recorded in such counters.
Camellia sinensis methanolic leaves extract: Phytochemical analysis and anticancer activity against human liver cancer cells
Authors: Hanna Demiana H. , Al-Atmani Ahlam K. , AlRashidi Aljazi Abdullah , Shafee E. El. 
Published: November 2024

Background
The study’s primary goal is to ascertain whether there is a relationship between the processed green tea methanolic extract’s (GTME) phytochemical components and its potential effectiveness against human liver cancer cells. The GTME’s phytochemical composition was identified using gas chromatography-mass spectrometry, and the extract’s capacity to lower cellular proliferation and cause apoptosis in HepG2 cancerous liver cell lines was checked.

Results
The findings of the gas chromatography-mass chromatogram showed that GTME included bioactive antioxidants and anticancer substances. Additionally, utilizing the MTT, comet assay, and acridine assay, GTME revealed a selective cytotoxic impact with a significant IC50 value (27.3 µg/ml) on HepG2 cells without any harmful effects on WI-38 healthy cells. Also, compared to untreated cells, the extract-treated HepG2 cells had an upsurge in the proportion of cells that have undergone apoptosis and displayed a comet nucleus, which is a sign of DNA damage. In addition, HepG2 cells treated with GTME revealed a stop in the G1 phase and sub-G1 apoptotic cells (37.32%) in a flow cytometry analysis. Furthermore, reactive oxygen species were shown to be responsible for HepG2 apoptosis, and the tested extract significantly reduced their levels in the treated cells. Lastly, compared to untreated cells in treated HepG2 cells, GTME significantly changed protein expression levels linked with cell cycle arrest in the G1 phase and apoptosis.

Conclusion
These findings provided information about the processes through which the GTME inhibited the growth of HepG2. Therefore, it has potential as an effective natural therapy for the treatment of human liver cancer. However, to validate these findings, animal models must be used for in vivo studies.
Individualised prediction of major bleeding in patients with atrial fibrillation treated with anticoagulation
Authors: Toft-Petersen Anne Pernille , J.-Y. Lee Christina , Phelps Matthew , Ozenne Brice , Gerds Thomas Alexander , Torp-Pedersen Christian 
Published: November 2024

Background
Anticoagulation in atrial fibrillation (AF) increases the risk of major bleeding. No predictive model has hitherto provided estimates of the absolute risk for individual patients.

Aim
To predict the individual 1-year risk of major bleeding in patients with AF taking anticoagulants and evaluate the importance of individual risk factors.

Design
A nationwide register-based cohort study.

Participants
Danish patients with first-time non-valvular AF who redeemed anticoagulants within 7 days after diagnosis.

Method
The individual absolute risk of major bleeding was estimated from a logistic regression model (the Calculator of Absolute Bleeding Risk/CABS model) utilising the same risk factors as HAS-BLED, except allowing non-linear age effects, and allowing effect modification of all factors according to history of bleeding. The logistic regression was assessed in term of discrimination using the Area Under the ROC curve (AUC) and calibration.

Results
Among 76,102 patients with AF redeeming anticoagulants, 2,406 suffered a major bleeding within 1 year. History of bleeding was the strongest predictor, and age significantly modified the risk. The CABS model superseded HAS-BLED score with regards to discrimination (AUC 0.646 vs 0.615, p<0.001) and calibrated well. A typical male patient was 70-years old without any risk factors and he had a 1-year bleeding risk of 1.4% (1.2; 1.6) while a typical female patient was 73-years old, had hypertension and a 1-year bleeding risk of 2.2% (1.9;2.6).

Conclusion
We propose CABS as a tool for prediction of individual absolute risks of major bleeding in patients with AF taking anticoagulant. The predicted absolute risk can be used for patient counselling.
The impact of financial incentives promoting biosimilar products in oncology: A quasi-experimental study using administrative data
Authors: Itoshima Hisashi , Takada Daisuke , Goto Etsu , Sasaki Noriko , Kunisawa Susumu , Imanaka Yuichi 
Published: November 2024

Background
Biosimilars have the potential to save a significant amount of money in cancer treatment costs. However, barriers exist in the adoption of biosimilar products. Japan introduced a new health policy in 2022 to promote the use of biosimilars in oncology by offering financial incentives to eligible hospitals. This study aims to examine the association between these financial incentives and prescription patterns.

Methods
The study analyzed Diagnosis Procedure Combination (DPC) data to assess the impact of the new health policy on the use of biosimilar products in oncology. The policy provided an additional fee for hospitals using biosimilar products. The study included patients with specific types of cancer and analyzed the proportion of monthly biosimilar prescriptions using the number of prescriptions of reference and biosimilar products. A generalized synthetic control method was used for analysis.

Results
From April 2020 to March 2023, the study involved 27,737 patients in 114 hospitals, with 63 eligible hospitals receiving financial incentives. The average number of prescriptions of the drugs (rituximab, trastuzumab, and bevacizumab) increased gradually in both eligible and ineligible hospitals. The financial incentives were associated with a significant increase in the proportion of biosimilar product prescriptions, with a monthly increase of 0.092 per month (95% CI, 0.040–0.145) [9.2%, 95% CI, 4.0–14.5] compared to ineligible hospitals.

Conclusion
Our study indicates that providing financial incentives to hospitals to utilize biosimilar products increased their prescriptions. Japan’s recent health policy of moderate financial incentives is an effective approach to increasing prescriptions of biosimilar products.
Parents’ knowledge and practices of child eye health care: A scoping review
Authors: Ghani Nor Diyana Hani , Mohamad Fadzil Norliza , Mohammed Zainora , Abd Rahman Mohd Harimi , Che Din Normah 
Published: November 2024

Background
Treating children’s eyes is not just a privilege for a child, it is an essential requirement for their visual health. Parents, as caregivers, have a paramount responsibility to make decisions regarding their children’s eye health. Thus, this review aims to identify and summarise published information about parents’ knowledge and practices on children’s eye health care.

Methods
Relevant articles searches were performed through a systematic search of databases (EBSCOhost, PubMed, and Scopus) using the keywords ‘knowledge’, ‘practice’, ‘parent’, ‘eye’, ‘problem’, and ‘children’. This review was conducted and reported in line with the PRISMA-ScR. The methodological quality of the listed studies was assessed using A Modified McMaster Critical Review form based on the total score.

Result
From a total of 235 studies retrieved through literature review and pearling, 219 remained after removing duplicates. After screening titles and abstracts, 204 irrelevant studies were excluded, leaving 15. After a detailed full-text review, four studies were excluded due to not meeting inclusion criteria. Thus, this review includes the remaining 11 studies. All eleven studies (n = 11) show that parents’s knowledge and practices vary. Some parents display good knowledge regarding children’s eye health care, for example, understanding the importance of wearing spectacles, the significance of children having normal vision, and where to seek eye examinations. Five studies (n = 5) showed that parents have good practices such as consulting doctors and seeking eye examinations and treatment at the hospital. Six studies (n = 6) showed that parents have misconceptions regarding knowledge, practices, and treatment of children’s eye health.

Conclusion
This scoping review found that parents’ knowledge and practices regarding children’s eye health are poor. Parents’ perceptions and practices about the cause and treatment of eye problems were tainted with misconceptions. Therefore, implementing structured programs to enhance awareness and promote the adoption of healthy practices for children’s eye health is required.