bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUBJECT-SPECIFIC KNEE JOINT MODELLING BETWEEN YOUNG AND ELDERLY
Authors: Han S.K. , Yoo Y.W. , Choi H. , Lee K.K. , Korhonen R.K. , Esrafilian A. 
Published: January 2024

It is known that the gait dynamics of elderly substantially differs from that of young people. However, it has not been well studied how this age-related gait dynamics affects the knee biomechanics, e.g., cartilage mechanical response. In this study, we investigated how aging affects knee biomechanics in a female population using subject-specific computational models.Two female subjects (ages of 23 and 69) with no musculoskeletal disorders were recruited. Korea National Institute for Bioethics Policy Review Board approved the study. Participants walked at a self-selected speed (SWS), 110% of SWS, and 120% of SWS on 10 m flat ground. Three-dimensional marker trajectories and ground reaction forces (Motion Analysis, USA), and lower limbs’ muscle activities were measured (EMG, Noraxon USA). Knee cartilage and menisci geometries were obtained from subjects’ magnetic resonance images (3T, GE Health Care). An EMG-assisted musculoskeletal finite element modeling workflow was used to estimate knee cartilage tissue mechanics in walking trials. Knee cartilage and menisci were modeled using a transversely isotropic poroviscoelastic material model.Walking speed in SWS, 110%, and 120% of SWS were 1.38 m/s, 1.51 m/s, and 1.65 m/s for the young, and 1.21 m/s, 1.34 m/s and 1.46 m/s for the elderly, respectively. The maximum tensile stress in the elderly tibial cartilage was ~25%, ~33%, and ~32% lower than the young at SWS, 110%, and 120% of SWS, respectively. These preliminary results suggest that the cartilage in the elderly may not have enough stimulation even at 20% increases in walking speed, which may be one reason for tissue degeneration. To enhance these findings, further study with more subjects and different genders will investigate how age-related gait dynamics affects knee biomechanics.Acknowledgments: Australian NHMRC Ideas Grant (APP2001734), KITECH (JE220006)
TRANSFECTION OF HMSCS WITH CHEMICALLY MODIFIED MRNA CODING FOR BMP-7 ENHANCES OSTEOGENESIS
Authors: Runzer C.D.T. , Sadowska J. , Plank C. , O'Brien F.J. , van Griensven M. , Balmayor E.R. 
Published: January 2024

Bone morphogenetic proteins (BMPs) have been widely investigated for treating non-healing fractures. They participate in bone reconstruction by inducing osteoblast differentiation, and osteoid matrix production.1 The human recombinant protein of BMP-7 was among the first growth factors approved for clinical use. Despite achieving comparable results to autologous bone grafting, severe side effects have been associated with its use.2 Furthermore, BMP-7 was removed from the market.3 These complications are related to the high doses used (1.5-40 miligrams per surgery)2 compared to the physiological concentration of BMP in fracture healing (in the nanogram to picogram per milliliter range).4 In this study, we use transcript therapy to deliver chemically modified mRNA (cmRNA) encoding BMP-7. Compared to direct use of proteins, transcript therapy allows the sustained synthesis of proteins with native conformation and true post-translational modifications using doses comparable to the physiological ones.5 Moreover, cmRNA technology overcomes the safety and affordability limitations of standard gene therapy i.e. pDNA.6 BMP-7 cmRNA was delivered using Lipofectamine™ MessengerMAX™ to human mesenchymal stromal cells (hMSCs). We assessed protein expression and osteogenic capacity of hMSCs in monolayer culture and in a house-made, collagen hydroxyapatite scaffold. Using fluorescently-labelled cmRNA we observed an even distribution after loading complexes into the scaffold and a complete release after 3 days. For both monolayer and 3D culture, BMP-7 production peaked at 24 hours post-transfection, however cells transfected in scaffolds showed a sustained expression. BMP-7 transfected hMSCs yielded significantly higher ALP activity and Alizarin red staining at later timepoints compared to the untransfected group. Interestingly, BMP-7 cmRNA treatment triggered expression of osteogenic genes like OSX, RUNX-2 and OPN, which was also reflected in immunostainings. This work highlights the relevance of cmRNA technology that may overcome the shortcomings of protein delivery while circumventing issues of traditional pDNA-based gene therapy for bone regeneration.Acknowledgement: This work has been performed as part of the cmRNAbone project and has received funding from the European Union's Horizon 2020 research and innovation programme under the Grant Agreement No 874790.
A NOVEL SELECTIVE PROSTAGLANDIN-RECEPTOR EP4-AGONIST PROMOTES SPINAL FUSION IN RATS
Authors: Vater C. , Tian X. , Findeisen L. , Raina D.B. , Kern H. , Bolte J. , Straßburger L. , Matuszewski L.-M. , Modler N. , Gottwald R. , Winkler A. , Schaser K.-D. , Disch A.C. , Zwingenberger S. 
Published: January 2024

A novel EP4 selective agonist (KMN-159) was developed [1] and has been proven that it can act as an osteopromotive factor to repair critical-size femoral bone defects in rats at a dose-dependent manner [2]. Based on its osteopromotive properties, we hypothesized that KMN-159 could also aid in bone formation for spinal fusion. Therefore, the aim of this study was to investigate its spinal fusion effect in a dorsolateral spinal fusion model in rats. This study was performed on 192, 10-week-old male Wistar rats. The rats were randomized into 8 groups (n = 12 per group): 1) SHAM (negative control), 2) MCM (scaffold only), 3) MCM + 20 µg BMP-2 (positive control), 4-8) MCM + 0.2, 2, 20, 200 or 2000 µg KMN-159. A posterolateral intertransverse process spinal fusion at L4 to L5 was performed bilaterally by implanting group dependent scaffolds (see above) or left empty in the SHAM group (protocol no. 25-5131/474/38). Animals were euthanized after 3 weeks and 6 weeks for µCT and biomechanical testing analysis. The results showed that KMN-159 promoted new bone formation in a dose-dependent manner at 3 weeks and 6 weeks as verified by µCT. The biomechanical testing showed that the dose of 20, 200 and 2000 µg KMN-159 groups obtained comparable strength with BMP-2 group, which higher than SHAM, MCM and lower doses of 0.2 and 2 µg KMN-159 groups. In conclusion, KMN-159 could be a potential replacement of BMP-2 as a novel osteopromotive factor for spinal fusion.Acknowledgements: We are grateful to Ulrike Heide, Anna-Maria Placht (assistance with surgeries) as well as Suzanne Manthey & Annett Wenke (histology).
MECHANICAL STIMULATION OF PIEZOELECTRIC SCAFFOLDS PROMOTES CELL OSTEOGENIC DIFFERENTIATION
Authors: Tavernaraki N.N. , Platania V. , Chatzinikolaidou M. 
Published: January 2024

Bone is a dynamic tissue that undergoes continuous mechanical forces. Mechanical stimuli applied on scaffolds resembling a part of the human bone tissue affects the osteogenesis [1]. Poly(3,4-ethylenedioxythiophene) (PEDOT) is a piezoelectric material that responds to mechanical stimulation producing an electrical signal, which in turn promotes the osteogenic differentiation of bone-forming cells by opening voltage-gated calcium channels [2]. In this study we examined the biological behavior of pre-osteoblastic cells seeded onto lyophilized piezoelectric PEDOT-containing scaffolds applying uniaxial compression.Two different concentrations of PEDOT (0.10 and 0.15% w/v) were combined with a 5% w/v poly(vinyl alcohol) (PVA) and 5% w/v gelatin, casted into wells, freeze dried and crosslinked with 2% v/v (3-glycidyloxypropyl)trimethoxysilane and 0.025% w/v glutaraldehyde. The scaffolds were physicochemically characterized by FTIR, measurement of the elastic modulus, swelling ratio and degradation rate. The cell-loaded scaffolds were subjected to uniaxial compression with a frequency of 1 Hz and a strain of 10% for 1 h every second day for 21 days. The loading parameters were selected to resemble the in vivo loading situation [3]. Cell viability and morphology on the PEDOT/PVA/gelatin scaffolds was determined. The alkaline phosphatase (ALP) activity, the collagen and calcium production were determined.The elastic modulus of PEDOT/PVA/gelatin scaffolds ranged between 1 and 5 MPa. The degradation rate indicates a mass loss of 15% after 21 days. The cell viability assessment displays excellent biocompatibility, while SEM images display well-spread cells. The ALP activity at days 3, 7 and 18 as well as the calcium production are higher in the dynamic culture compared to the static one. Moreover, energy dispersive spectroscopy analysis revealed the presence of calcium phosphate in the extracellular matrix after 14 days. The results demonstrate that PEDOT/PVA/gelatin scaffolds promote the adhesion, proliferation, and osteogenic differentiation of pre-osteoblastic cells under mechanical stimulation, thus favoring bone regeneration.
The CREB1 inhibitor 666-15 maintains cartilage homeostasis and mitigates osteoarthritis progression
Authors: Wang Ying , Wu Zhimin , Yan Guoqiang , Li Shan , Zhang Yanzhuo , Li Guangping , Wu Chengai 
Published: January 2024

AimscAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect.MethodsCREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA).ResultsCREB1 was hyperactive in osteoarthritic articular cartilage, interleukin (IL)-1β-treated cartilage explants, and IL-1β- or carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-treated chondrocytes. 666-15 enhanced cell viability of OA-like chondrocytes and alleviated IL-1β- or CCCP-induced chondrocyte injury through inhibition of mitochondrial dysfunction-associated apoptosis. Moreover, inhibition of CREB1 by 666-15 suppressed expression of ADAMTS4. Additionally, 666-15 alleviated joint degeneration in an ACLT mouse model.ConclusionHyperactive CREB1 played a critical role in OA development, and 666-15 exerted anti-IL-1β or anti-CCCP effects in vitro as well as joint-protective effects in vivo. 666-15 may therefore be used as a promising anti-OA drug.Cite this article: Bone Joint Res 2024;13(1):4–18.
Parameter-free fiber coupling method for inter-satellite laser communications based on Gaussian approximation
Authors: Li Ziqiang , Pan Ziting , Li Yuting , Yang Xu , Li Feng , Geng Chao , Li Xinyang 
Published: January 2024

Satellite constellation networks play a pivotal role in making Beyond 5G services universally accessible to people worldwide. Inter-satellite laser communication is a crucial component of satellite communication networks. To utilize fiber amplifiers, it is imperative to couple the free-space optical beam into a single-mode fiber. However, vibrations and non-coaxial errors significantly impact coupling efficiency, thereby affecting communication quality. We have developed a parameter-free fiber coupling method based on Gaussian approximation to rectify non-coaxial errors and mitigate incident angle deviations induced by vibrations, ensuring consistently high coupling efficiency. This method is fast, stable, and parameter-free, eliminating the need for manual intervention. Furthermore, experimental results demonstrate the method’s effectiveness across the entire correction range of the correction device. In environments with strong vibrations, the communication link experiences a bit error rate of 6.734 E-2, which is reduced to zero bit errors after implementing this method in a closed loop.
Multiplexed wavefront sensing with a thin diffuser
Authors: Wu Tengfei , Guillon Marc , Tessier Gilles , Berto Pascal 
Published: January 2024

In astronomy or biological imaging, refractive index inhomogeneities of, e.g., atmosphere or tissues, induce optical aberrations that degrade the desired information hidden behind the medium. A standard approach consists of measuring these aberrations with a wavefront sensor (e.g., Shack–Hartmann) located in the pupil plane, and compensating for them either digitally or by adaptive optics with a wavefront shaper. However, in its usual implementation this strategy can only extract aberrations within a single isoplanatic patch, i.e., a region where the aberrations remain correlated. This limitation severely reduces the effective field-of-view in which the correction can be performed. Here, we propose a wavefront sensing method capable of measuring, in a single shot, various pupil aberrations corresponding to multiple isoplanatic patches. The method, based on a thin diffuser (i.e., a random phase mask), exploits the dissimilarity between different speckle regions to multiplex several wavefronts incoming from various incidence angles. We present proof-of-concept experiments carried out in widefield fluorescence microscopy. A digital deconvolution procedure in each isoplanatic patch yields accurate aberration correction within an extended field-of-view. This approach is of interest for adaptive optics applications as well as diffractive optical tomography.
Micro-opto-mechanical glass interferometer for megahertz modulation of optical signals
Authors: Memeo Roberto , Crespi Andrea , Osellame Roberto 
Published: January 2024

Waveguide-based interferometric circuits are widely employed in optical communications, sensing, and computing applications. In particular, glass-based devices are appealing due to the transparency and bio-compatibility of this substrate, or where low-loss interfacing with fiber networks is required. However, fast electro-optic phase modulation is hard to achieve in glass materials. Here, we demonstrate an optical phase and intensity modulator in glass, working in the megahertz range. This modulator exploits the elasto-optic effect inside a mechanical microstructure, brought to oscillation at resonance, and is entirely realized by femtosecond laser micromachining. In detail, we demonstrate 23-dB optical intensity modulation at 1.17 MHz, with an internal optical loss of the phase-modulator component as low as 0.04 dB.
Micropulse cyclophotocoagulation compared to continuous wave cyclophotocoagulation for the management of refractory pediatric glaucoma
Authors: Wang Bo , Wallace Ryan T. , Musser John A. , Chaya Craig J. , Kraus Courtney L. 
Published: January 2024

Introduction
Micropulse cyclophotocoagulation (MPCPC) has been shown in adults to offer a favorable post-operative safety profile compared to continuous wave transscleral cyclophotocoagulation (CWCPC) in the management of glaucoma. The purpose of this study is to evaluate the long term efficacy, safety, and effectiveness of MPCPC in the management of pediatric glaucoma when compared to CWCPC.

Methods
IRB approved retrospective chart review of patients with pediatric glaucoma that underwent MPCPC and CWCPC at 2 separate institutions. Success was defined as intraocular pressure (IOP) between 5 and 21mmHg on any number of topical glaucoma medication without requiring additional surgical intervention or oral IOP lowering medication.

Results
Of the 48 patients in the study, 22 (26 eyes) underwent MPCPC and 26 (30 eyes) underwent CWCPC. At 1 year, 7 out of 26 eyes (26.9%) achieved success in the MPCPC group compared to 13 out of 30 eyes (43.3%) in the CWCPC group. Survival analysis unveiled a statistically significant difference in success between the two groups (p = 0.03).

Conclusion
In pediatric glaucoma patients undergoing cyclophotocoagulation procedures, CWCPC outperformed MPCPC using default settings in terms of achieving long-term IOP control. Additional studies are required to evaluated augmented MPCPC settings in pediatric glaucoma patients.
Factors associated with the acceptability of Lopinavir/Ritonavir formulations among children living with HIV/AIDS attending care and treatment clinics in Mbeya and Mwanza, Tanzania
Authors: Jiwa Nadiya Alnoor , Ketang’enyi Eunice , Nganyanyuka Kapongola , Mbwanji Ruth , Mwenisongole Danistan , Masuka Eutropia , Brown Mary , Charles Mary , Mwasomola Davance Leonard , Nyangalima Thomas , Olomi Willyhelmina , Komba Lilian , Gwimile Judith , Kasambala Bertha , Mwita Lumumba 
Published: January 2024

Introduction
Children living with chronic illnesses are offered formulations based on manufacturer and distributor research. The aim of this study is to better understand the perspectives of children and their caregivers in accepting Lopinavir/ritonavir (LPV/r) formulations.

Methods
362 participants were recruited from two pediatric HIV/AIDS clinics in Mbeya and Mwanza, Tanzania, from December 2021 to May 2022. A translated questionnaire was piloted and validated at both clinics, followed by the implementation of a cross-sectional study.

Results
169 participants (47.1%) reported general difficulties in swallowing, regardless of formulation, while 34.3% and 38.5% reported vomiting tablets and syrups, respectively. Statistical significance is shown to support that children can swallow medications if they can eat stiffened porridge (Ugali). This correlated with the lower incidence of younger children being able to swallow compared to older children (above six years of age). Children older than six years preferred taking tablets (independent of daily dosage) better than other formulations. Significantly, older children who attend school were associated with high odds of swallowing medicine (AOR = 3.06, 95%CI; 1.32–7.05); however, age was not found to be statistically related to ease of administration for Lopinavir/Ritonavir in this study.

Conclusions
Lopinavir/Ritonavir tablets remain the most accepted formulation among children and adolescents with HIV/AIDS. This study highlights the impact of various factors affecting the acceptability of pediatric formulation, suggesting that children younger than six years, unable to eat Ugali and not attending schools may be most vulnerable regarding their ability to accept Lopinavir/Ritonavir formulations. Further studies are needed to assess the acceptability of other medications in chronically ill children.
Liver transplant recipients with polycystic liver disease have longer waiting times but better long-term clinical outcomes than those with liver disease due to other causes: A retrospective cross-sectional study
Authors: Gittus Matt , Moore Joanna , Ong Albert C. M. 
Published: January 2024

Introduction
Liver transplantation is the only curative option for patients with polycystic liver disease (PLD). In the United Kingdom, these patients are listed on the variant syndrome list due to their preserved liver function reflected in the United Kingdom End-stage Liver Disease (UKELD) score. The transplantation and survival rates for this patient group in the UK have not been previously reported.

Methods
A retrospective cross-sectional analysis of patients receiving liver transplantation between 2010 and 2017 was performed using the NHS blood and transplantation database. This database contains the demographic, clinical parameters, indication for transplantation and follow-up of all patients in UK-based transplant centres. Basic statistics was performed using SPSS version 27.

Results
5412 recipients received elective liver allografts in the study period. 1.6% (100) of recipients had PLD as their primary indication for transplantation with 60 receiving liver only allografts and 40 receiving combined liver-kidney allografts. PLD patients had a >3-fold longer mean waiting time for transplantation compared to non-PLD patients, 508 days v 154 days respectively. PLD patients receiving combined liver-kidney allografts had a longer waiting time than those receiving a liver only allograft, 610 days v 438 days respectively. There were comparable patient survival rates for people with PLD and non-PLD primary indications at 30 days (94.0% vs 97.6%) and 1 year (92.0% vs 93.2%) but improved survival rates at 5 years (81.3% vs 76.5%). There were also comparable allograft survival rates for people with PLD and non-PLD primary indications at 30 days (93.9% vs 95.3%) and 1 year (91.9% vs 91.2%) but improved survival rates at 5 years (82.5% vs 77.3%). Transplant centre-level analysis identified variation in the proportion of liver transplantations for people with PLD as their primary listed indication.

Conclusions
Patients with PLD wait significantly longer for liver transplantation compared to other indications. However, transplanted PLD patients demonstrate better longer-term patient and liver allograft survival rates compared to transplanted non-PLD patients. The unexpected variation between individual UK centres transplanting for PLD deserves further study.
Diagnostic psychiatric and somatic comorbidity in patients with depression in the Western Balkan countries
Authors: Latas Milan , Stefanovski Branko , Mihaljević-Peleš Alma , Memić Serdarević Amra , Pajević Izet , Radulović Nera Zivlak , Radulović Sabina , Đukić Bojana , Korugić Vasilije , Jovandić Željko 
Published: January 2024

Introduction
This paper aims to examine the frequency and significance of diagnostic comorbidity of psychiatric disorders and somatic diseases in a sample of patients with depression as well as present current psychopharmacological treatment of the patients in the sample.

Methods
The subjects in this study sample were 489 patients from the four Western Balkan countries with current primary diagnosis of major depression according to ICD 10. Comorbid psychiatric disorders and non-psychiatric illnesses were noted according to ICD 10 criteria during the diagnostic interview and analysed later. Additionally, the pharmacological treatment (existing and newly introduced) for each patient was noted and analysed later.

Results
At least one comorbid psychiatric disorder was present in 72.5% of patients. The most frequent were anxiety disorders (53.6%), specifically generalized anxiety disorder (20.2%); non-organic sleep disorders (50.7%), specifically insomnia (48.4%); and sexual dysfunctions (21.4%), specifically lack of sexual desire (20.2%). Comorbidity with any non-psychiatric illness was present in 80.3% of patients. The most frequent were circulatory system diseases (55.9%), specifically hypertension (45.9%); endocrine, nutritional and metabolic disorders (51.3%), specifically hyperlipidaemia (24.0%); and other non-psychiatric disorders (60.7%), specifically low back pain (22.7%). All patients received pharmacological treatment with different medications. Most patients received monotherapy or combination therapy of antidepressants, anxiolytics, antipsychotics and antiepileptics. The most frequently used antidepressants were escitalopram, sertraline, and duloxetine. The most frequently used anxiolytics were alprazolam and diazepam, the most used antiepileptic was pregabalin, and the most used antipsychotics were olanzapine, quetiapine, and aripiprazole.

Conclusion
The results of the study confirm the results of previous research studies about the high prevalence of psychiatric and non-psychiatric comorbidities in patients with depression that were conducted in the past. It would be important if future studies could prove the importance of those comorbidities on clinical severity, choice of treatment, and its outcome in patients with depression.