bluuebunny/crossref_metadata_2025 huggingface dataset:
MULTICELLULAR SPHEROID ENGINEERING USING BIOINSPIRED MATERIALS FOR OSTEOCHONDRAL TISSUE REGENERATION
Authors: Shin H.
Published: January 2024

Recently, technologies to culture one or more cell types in three dimensions have attracted a great deal of attention in tissue engineering. Particularly, the improved viability, self-renewal capacity, and differentiation potential have been reported for stem cell spheroids. However, it is crucial to modulate spheroid functions with instructive signals to use multi-cellular spheroids in tissue engineering. We have been developing ECM-mimicking fibrous materials decorated with cell-instructive cues, which were incorporated within 3D stem cell spheroids to fine-tune their functions as modular building blocks for bottom-up tissue-engineering applications. In particular, we created composite spheroids of human adipose-derived stem cells (hADSCs) incorporating nanofibers coated with instructive signal of either transforming growth factor-β3 or bone morphogenetic growth factor-2 for chondrogenesis or osteogenesis of stem cells, respectively. The bilayer structure of osteochondral tissue was subsequently mimicked by cultivating each type of spheroid inside 3D-printed construct. The in vitro chondrogenic or osteogenic differentiation of hADSCs within the biphasic construct under general media was locally regulated by each inductive component. More importantly, hADSCs from each spheroid proliferated and sprouted to form the integrated tissue with interface of bone and cartilage tissue. This approach may be applied to engineer complex tissue with hierarchically organized structure.
NEW-GENERATION SUPERIOR SINGLE PLATING VERSUS LOW-PROFILE DUAL MINI-FRAGMENT PLATING OF DIAPHYSEAL CLAVICLE FRACTURES: A BIOMECHANICAL STUDY
Authors: Pastor T. , Zderic I. , Berk T. , Souleiman F. , Vögelin E. , Beeres F.J.P. , Gueorguiev B. , Pastor T.
Published: January 2024

Recently, a new generation of superior clavicle plates was developed featuring the variable-angle locking technology for enhanced screw positioning and optimized plate-to-bone fit design. On the other hand, mini-fragment plates used in dual plating mode have demonstrated promising clinical results. However, these two bone-implant constructs have not been investigated biomechanically in a human cadaveric model. Therefore, the aim of the current study was to compare the biomechanical competence of single superior plating using the new generation plate versus dual plating with low-profile mini-fragment plates.

Sixteen paired human cadaveric clavicles were assigned pairwise to two groups for instrumentation with either a 2.7 mm Variable Angle Locking Compression Plate placed superiorly (Group 1), or with one 2.5 mm anterior plate combined with one 2.0 mm superior matrix mandible plate (Group 2). An unstable clavicle shaft fracture AO/OTA15.2C was simulated by means of a 5 mm osteotomy gap. All specimens were cyclically tested to failure under craniocaudal cantilever bending, superimposed with bidirectional torsion around the shaft axis and monitored via motion tracking.

Initial stiffness was significantly higher in Group 2 (9.28±4.40 N/mm) compared to Group 1 (3.68±1.08 N/mm), p=0.003. The amplitudes of interfragmentary motions in terms of craniocaudal and shear displacement, fracture gap opening and torsion were significantly bigger over the course of 12500 cycles in Group 1 compared to Group 2; p≤0.038. Cycles to 2 mm shear displacement were significantly lower in Group 1 (22792±4346) compared to Group 2 (27437±1877), p=0.047.

From a biomechanical perspective, low-profile 2.5/2.0 dual plates demonstrated significantly higher initial stiffness, less interfragmentary movements, and higher resistance to failure compared to 2.7 single superior variable-angle locking plates and can therefore be considered as a useful alternative for diaphyseal clavicle fracture fixation especially in unstable fracture configurations.
THE KNEE-HIP-SPINE TRILEMMA IN PATIENTS WITH SEVERE CONGENITAL DYSPLASIA OF THE HIP UNDERGOING TOTAL HIP ARTHROPLASTY: 77 HIPS FOLLOWED UP FOR A MINIMUM OF FIVE YEARS
Authors: García-Rey E. , Gómez-Barrena E.
Published: January 2024

Pelvic bone defect in patients with severe congenital dysplasia of the hip (CDH) lead to abnormalities in lumbar spine and lower limb alignment that can determine total hip arthroplasty (THA) patients' outcome. These variables may be different in uni- or bilateral CDH.

We compared the clinical outcome and the spinopelvic and lower limb radiological changes over time in patients undergoing THA due to uni- or bilateral CHD at a minimum follow-up of five years.

Sixty-four patients (77 hips) undergoing THA due to severe CDH between 2006 and 2015 were analyzed: Group 1 consisted of 51 patients with unilateral CDH, and group 2, 113 patients (26 hips) with bilateral CDH. There were 32 females in group 1 and 18 in group 2 (p=0.6). The mean age was 41.6 years in group 1 and 53.6 in group 2 (p<0.001). We compared the hip, spine and knee clinical outcomes. The radiological analysis included the postoperative hip reconstruction, and the evolution of the coronal and sagittal spinopelvic parameters assessing the pelvic obliquity (PO) and the sacro-femoro-pubic (SFP) angles, and the knee mechanical axis evaluating the tibio-femoral angle (TFA).

At latest follow-up, the mean Harris Hip Score was 88.6 in group 1 and 90.7 in group 2 (p=0.025). Postoperative leg length discrepancy of more than 5 mm was more frequent in group 1 (p=0.028). Postoperative lumbar back pain was reported in 23.4% of the cases and knee pain in 20.8%, however, there were no differences between groups. One supracondylar femoral osteotomy and one total knee arthroplasty were required. The radiological reconstruction of the hip was similar in both groups. The PO angle improved more in group 1 (p=0.01) from the preoperative to 6-weeks postoperative and was constant at 5 years. The SFP angle improved in both groups but there were no differences between groups (p=0.5). 30 patients in group 1 showed a TFA less than 10º and 17 in group 2 (p=0.7).

Although the clinical outcome was better in terms of hip function in patients with bilateral CDH than those with unilateral CDH, the improvement in low back and knee pain was similar. Patients with unilateral dysplasia showed a better correction of the PO after THA. All spinopelvic and knee alignment parameters were corrected and maintained over time in most cases five years after THA.
CELL-DERIVED EXTRACELLULAR MATRIX TAILORING FOR INTERVERTEBRAL DISC REGENERATION
Authors: Milheiro C. , Gonçalves R.M. , Amendola M. , Barbosa M. , Caldeira J.
Published: January 2024

Intervertebral disc (IVD) degeneration is characterized by tissue loss of function and major structural changes, which can lead to Low Back Pain. Current treatments fail to tackle the disc's hindered function and degenerative alterations. Our goal is to promote IVD regeneration, through the recapitulation of a fetal-like microenvironment based on a tailored cell-derived matrix (CDM), rich in two fetal exclusive collagens – COLXII and COLXIV. We hypothesize that this engineered CDM will have a pro-regenerative potential and allow IVD functional restoration. Immortalized mesenchymal stromal/stem cells (iMSCs) were transduced with the CRISPR/dCas9-VP64 lentiviral system, targeting COL12A1 or COL14A1. Gene and protein expression were evaluated by qRT-PCR, Western Blot and immunofluorescence. Simultaneously, optimization of CDM decellularization protocol was performed. Process efficacy was validated by immunofluorescence. DNA content was quantified using the Quant-iT™ PicoGreen™ Kit. Successful iMSCs engineering was confirmed by an average increase of mRNA relative expression for both collagens (2.12-fold for COL12A1 and 11.7-fold for COL14A1). Protein level assessment by western blot and immunofluorescence confirmed increased COLXII and COLXIV. Decellularized CDM production was optimized. Cell removal was demonstrated by nuclear and actin staining reduction, when compared with the non-decellularized control. DNA content showed a marked decrease in both NH4OH- and SDS-based protocols. Matrix preservation after decellularization was confirmed by fibronectin staining only in the NH4OH-based decellularization. Preliminary proteomic characterization data of engineered iMSCs as shown some functional impact namely on Sonic Hedgehog (Shh) pathway and repression of pain by DREAM (Downstream regulator element antagonist modulator). In conclusion, we were able to establish a CRISPR activating system for COL12A1 and COL14A1, allowing the use of iMSCs as biofactories for a IVD fetal-tailored CDM. The use of a customized ECM and fetal microenvironment recapitulations is an innovative strategy for IVD functional restoration, and its versatility opens new avenues in the tissue regeneration field.
ADVANCED BIOREACTOR STUDIES OF REGION-SPECIFIC RESPONSE IN THE INTERVERTEBRAL DISC TO COMPRESSION, FLEXION/EXTENSION, AND TORSION
Authors: Šećerović A. , Ristaniemi A. , Crivelli F. , Heub S. , Weder G. , Ferguson S.J. , Ledroit D. , Grad S.
Published: January 2024

Intervertebral disc (IVD) degeneration is inadequately understood due to the lack of in vitro systems that fully mimic the mechanical and biological complexity of this organ. We have recently made an advancement by developing a bioreactor able to simulate physiological, multiaxial IVD loading and maintain the biological environment in ex vivo IVD models [1].

To validate this new bioreactor system, we simulated natural spine movement by loading 12 bovine IVDs under a combination of static compression (0.1 MPa), cyclic flexion/extension (±3˚, ±6˚ or 0-6˚) and cyclic torsion (±2˚, ±4˚ or 0-4˚) for more than 10’000 (0.2 Hz) or 100’000 (1 Hz) cycles over 14 days. A higher number of cycles increased the release of glycosaminoglycans and nitric oxide, as an inflammation marker, whereas fewer cycles maintained these two factors at physiological levels. All applied protocols upregulated the expression of MMP13 in the outermost annulus fibrosus (AF), indicating a collagen degradation response. This was supported by fissures observed in the AF after a longer loading duration. Increasing loading cycles induced high cell death in the nucleus pulposus and inner AF, while with fewer cycles, high cell viability was maintained in all IVD regions, irrespective of the magnitude of rotation.

Less frequent multiaxial loading maintains IVD homeostasis while more frequent loading initiates an IVD degenerative profile. Specifically, the morphological and molecular changes were localized in the AF, which can be associated with combined flexion/extension and torsion. More loading cycles induced region-specific cell death and a higher release of extracellular matrix molecules from the innermost IVD regions, likely associated with longer exposure to static compression. Altogether, we demonstrated the advantages of the multiaxial bioreactor to study region-specific response in the IVD, which will allow a more profound investigation of IVD degeneration under different combinations of motions.
A NEW TISSUE-ENGINEERED PRODUCT INDICATED FOR BONE RECONSTRUCTION: PROOF OF CONCEPT
Authors: Mbuku R.B. , Sanchez C. , Evrard R. , Englebert A. , Manon J. , Henriet V. , Nolens G. , Duy K.T. , Schubert T. , Henrotin Y. , Cornu O.
Published: January 2024

To design slow resorption patient-specific bone graft whose properties of bone regeneration are increased by its geometry and composition and to assess it in in-vitro and in-vivo models.

A graft composed by hydroxyapatite (HA) and β-TCP was designed as a cylinder with 3D gyroid porosities and 7 mm medullary space based on swine's anatomy. It was produced using a stereolithography 3D-printing machine (V6000, Prodways).

Sterile bone grafts impregnated with or without a 10µg/mL porcine BMP-2 (pBMP-2) solution were implanted into porcine femurs in a bone loss model. Bone defect was bi-weekly evaluated by X-ray during 3 months. After sacrifice, microscanner and non-decalcified histology analysis were conducted on biopsies.

Finally, osteoblasts were cultured inside the bone graft or in monolayer underneath the bone graft. Cell viability, proliferation, and gene expression were assessed after 7 and 14 days of cell culture (n=3 patients).

3D scaffolds were successfully manufactured with a composition of 80% HA and 20% β-TCP ±5% with indentation compressive strength of 4.14 MPa and bending strength of 11.8MPa.

In vivo study showed that bone regeneration was highly improved in presence of pBMP-2. Micro-CT shows a filling of the gyroid sinuses of the implant (Figure 1).

In vitro, the presence of BMP2 did not influence the viability of the osteoblasts and the mortality remained below 3%. After 7 days, the presence of BMP2 in the scaffold significantly increased by 85 and 65% the COL1A1 expression and by 8 and 33-fold the TNAP expression by osteoblasts in the monolayer or in the scaffold, respectively. This BMP2 effect was transient in monolayer and did not modify gene expression at day 14.

BMP2-impregnated bone graft is a promising patient-personalized 3D-printed solution for bone defect regeneration, by promoting neighboring host cells recruitment and solid new bone formation.

For any figures and tables, please contact the authors directly.
BONE TISSUE REGENERATION INDUCED BY LOCAL DELIVERY OF BONE MORPHOGENETIC PROTEIN 2 FROM PRO-ANGIOGENIC NEAR-INFRARED-RESPONSIVE HYDROGELS
Authors: Escudero-Duch C. , Serrano-Yamba R. , Sánchez-Casanova S. , Falguera-Uceda M. , Yus C. , Lerma-Juárez M.A. , Arruebo M. , Vilaboa N.
Published: January 2024

In this work, we combined tissue engineering and gene therapy technologies to develop a therapeutic platform for bone regeneration. We have developed photothermal fibrin-based hydrogels that incorporate degradable CuS nanoparticles (CuSNP) which transduce incident near-infrared (NIR) light into heat. A heat-activated and rapamycin-dependent transgene expression system was incorporated into mesenchymal stem cells to conditionally control the production of bone morphogenetic protein 2 (BMP-2). Genetically engineered cells were entrapped in the photothermal hydrogels. In the presence of rapamycin, photoinduced mild hyperthermia induced the release of BMP-2 from the NIR responsive cell constructs. Transcriptome analysis of BMP-2 expressing cells showed a signature of induced genes related to stem cell proliferation and angiogenesis. We next generated 4 mm diameter calvarial defects in the left parietal bone of immunocompetent mice. The defects were filled with NIR-responsive hydrogels entrapping cells that expressed BMP-2 under the control of the gene circuit. After one and eight days, rapamycin was administered intraperitoneally followed by irradiation with an NIR laser. Ten weeks after implantation, the animals were euthanized and samples from the bone defect zone were processed for histological analysis using Masson's trichrome staining and for immunohistochemistry analyses using specific CD31 and CD105 antibodies. Samples from mice that were only administered rapamycin or vehicle or that were only NIR-irradiated showed the persistence of fibrous tissue bridging the defect. In animals that were treated with rapamycin, NIR irradiation of implants resulted in the formation of new mineralized tissue with a high degree of vascularization, thus indicating the therapeutic potential of the approach.

Acknowledgements: This research was supported by grants RTI2018-095159-B-I00 and PID2021-126325OB-I00 (MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe”), by grant P2022/BMD- 7406 (Regional Government of Madrid). M.A.L-J. is the recipient of predoctoral fellowship PRE2019-090430 (MCIN/AEI/10.13039/501100011033).
TOWARDS FUNCTIONAL PATIENT-DERIVED ORGANOIDS AS MODELS FOR SOFT-TISSUE JOINT DISEASE
Authors: Dvorak N.
Published: January 2024

In-vitro models of disease are valuable tools for studying disease and analysing response to therapeutics. Recently, advances in patient-derived organoid (PDO) models have been shown to faithfully recapitulate structure, function, and therapeutic response for a wide range of tissues. Frozen shoulder is a rare example of a chronic inflammatory fibrotic disease which is self-limiting, unlike many other soft tissue fibrotic disorders. As no in-vitro 3D models or in-vivo animal models exist for frozen shoulder, establishing an organoid model which recapitulates core diseases features may give insight into fibrosis resolution. Consequently, using biocompatible hydrogels, primary capsular fibroblasts, monocyte-derived macrophages and HUVEC cells, we generated stable PDO cultures which exhibited key disease phenotypes, including vascularization, increased stiffness, and an expanded lining layer over 21 days of culture. Through further investigation of cell-matrix and cell-cell interactions in the organoid model, we intend to unpack the differences between resolving and non-resolving fibrotic disease and uncover clinically relevant therapeutic targets for fibrosis.
ULTRASOUND COUNTERACTS INFLAMMATION AND INDUCES CHONDROGENIC DIFFERENTIATION OF ASCS IN 3D PIEZOELECTRIC HYDROGELS
Authors: Manferdini C. , Gabusi E. , Dolzani P. , Trucco D. , Lenzi E. , D'Atri G. , Vannozzi L. , Cafarelli A. , Ricotti L. , Lisignoli G.
Published: January 2024

In cartilage tissue engineering (TE),new solutions are needed to effectively drive chondrogenic differentiation of mesenchymal stromal cells in both normal and inflammatory milieu. Ultrasound waves represent an interesting tool to facilitate chondrogenesis. In particular, low intensity pulsed ultrasound (LIPUS)has been shown to regulate the differentiation of adipose mesenchymal stromal cells. Hydrogels are promising biomaterials capable of encapsulating MSCs by providing an instructive biomimetic environment, graphene oxide (GO) has emerged as a promising nanomaterial for cartilage TE due to its chondroinductive properties when embedded in polymeric formulations, and piezoelectric nanomaterials, such as barium titanate nanoparticles (BTNPs),can be exploited as nanoscale transducers capable of inducing cell growth/differentiation. The aim of this study was to investigate the effect of dose-controlled LIPUS in counteracting inflammation and positively committing chondrogenesis of ASCs embedded in a 3D piezoelectric hydrogel.

ASCs at 2*106 cells/mL were embedded in a 3D VitroGel RGD® hydrogel without nanoparticles (Control) or doped with 25 µg/ml of GO nanoflakes and 50 µg/ml BTNPs.The hydrogels were exposed to basal or inflammatory milieu (+IL1β 10ng/ml)and then to LIPUS stimulation every 2 days for 10 days of culture. Hydrogels were chondrogenic differentiated and analyzed after 2,10 and 28 days. At each time point cell viability, cytotoxicity, gene expression and immunohistochemistry (COL2, aggrecan, SOX9, COL1)and inflammatory cytokines were evaluated.

Ultrasound stimulation significantly induced chondrogenic differentiation of ASCs loaded into 3D piezoelectric hydrogels under basal conditions: COL2, aggrecan and SOX9 were significantly overexpressed, while the fibrotic marker COL1 decreased compared to control samples. LIPUS also has potent anti-inflammatory effects by reducing IL6 and IL8 and maintaining its ability to boost chondrogenesis.

These results suggest that the combination of LIPUS and piezoelectric hydrogels promotes the differentiation of ASCs encapsulated in a 3D hydrogel by reducing the inflammatory milieu, thus representing a promising tool in the field of cartilage TE.

Acknowledgements: This work received funding from the European Union's Horizon 2020 research and innovation program, grant agreement No 814413, project ADMAIORA (AdvanceD nanocomposite MAterIals for in situ treatment and ultRAsound-mediated management of osteoarthritis).
ELECTRICAL STIMULATION COMBINED WITH ADDITIVE MANUFACTURED 3D CONDUCTIVE SCAFFOLDS TOWARDS IMPROVED BONE-TISSUE ENGINEERING STRATEGIES
Authors: Silva J.C. , Garrudo F.F.F. , Meneses J. , Marcelino P. , Barbosa F. , Moura C.S. , Alves N.M. , Pascoal-Faria P. , Ferreira F.C.
Published: January 2024

The growing number of non-union fractures in an aging population has increased the clinical demand for tissue-engineered bone. Electrical stimulation (ES) has been described as a promising strategy for bone regeneration treatments in several clinical studies. However the underlying mechanism by which ES augments bone formation is still poorly understood and its use in bone tissue engineering (BTE) strategies is currently underexplored. Additive manufacturing (AM) technologies (Fused Deposition Modeling/3D Printing) have been widely used in BTE due to their ability to fabricate scaffolds with a high control over their structural and mechanical properties in a reproducible and scalable manner. Thus, in this work, we combined AM methods with conductive biomaterials and ES to enhance the osteogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells (hBMSCs) envisaging improved BTE strategies.

First, we started by developing AM-based electro-bioreactor devices containing medical-grade electrodes (stainless steel and Ti6Al4V) to apply ES to monolayer 2D cultures and 3D cell-seeded scaffolds. Computer modeling(Finite Element Analysis-FEA) was employed to predict the magnitude/distribution of electrical fields within the ES devices and along the different conductive scaffolds. Prior to scaffold culture, 5 different ES protocols were tested in terms of their ability to promote hBMSCs proliferation and osteogenic differentiation in 2D cultures. The best performance ES protocol was then used in two different AM-based BTE strategies: 1) Two different conductive scaffolds (conductive poly lactic acid (PLA) and titanium) were seeded with hBMSCs and cultured for 21 days under osteogenic medium conditions with and without ES and their biological performance was evaluated in comparison to non-conductive standard PLA scaffolds; 2) Different PEDOT:PSS-based coating solutions were screened to obtain PEDOT:PSS/Gelatin-coated 3D polycaprolactone (PCL) scaffolds with a high(11 S.cm-1) and stable electroconductivity. When cultured under ES, PEDOT:PSS/Gelatin-PCL scaffolds enhanced significantly hBMSCs osteogenic differentiation and mineralization(calcium deposition), highlighting their potential for BTE applications.

Acknowledgements: Funding received from FCT through projects InSilico4OCReg (PTDC/EME-SIS/0838/2021), OptiBioScaffold (PTDC/EME-SIS/4446/2020) and BioMaterARISES (EXPL/CTM-CTM/0995/2021), and to the institutions iBB (UIDB/04565/2020), CDRSP (UIDB/04044/2020) and Associate Laboratory i4HB (LA/P/0140/2020).
Management of Lateral Femoral Condyle Non-union with Autogenous Bone Graft in CAS Total Knee Arthroplasty
Authors:   Department of Joint Replacement Services, Joint Replacement Services, Fortis Escorts Hospital, Jaipur, Rajasthan, India., Jhurani Anoop , Agarwal Piyush ,   Department of Joint Replacement Services, Joint Replacement Services, Fortis Escorts Hospital, Jaipur, Rajasthan, India., Sahni Hardik ,   Department of Joint Replacement Services, Joint Replacement Services, Fortis Escorts Hospital, Jaipur, Rajasthan, India., Krishnamurthy Kanagasarathy ,   Department of Joint Replacement Services, Joint Replacement Services, Fortis Escorts Hospital, Jaipur, Rajasthan, India.
Published: January 2024

Introduction: Neglected distal femur fractures often present with significant uncontained bone defects of the lateral femoral condyle (LFC) leading to a valgus deformity and lateral compartment arthritis. Case Report: Bone defect can be managed with the help of autogenous bone graft harvested from a distal femur cut and shaped in the form of an augment. The objective of using bone graft along with the primary femur was to restore bone stock in a young patient and prevent the use of an augment with a revision femur and intramedullary rod. Conclusion: The use of computer navigation helped in getting accurate components and overall alignment thus facilitating compression at the bone graft site and early union. Keywords: Lateral femoral condyle fracture, bone graft, computer navigation.
Cross-beam Non-vascular Fibular Graft Reconstruction in the Management of Long Bone Giant Aneurysmal Bone Cyst – A Case Series
Authors:   Department of Orthopaedics, Thiruvallur Medical College, Thiruvallur, Tamil Nadu, India,, Annamalai Saravanan , Kandasamy Velmurugan ,   Department of Orthopaedics, Government Kilpauk Medical College, Chennai, Tamil Nadu, India,, Chandrasekaran Srinivasacholan ,   Department of Orthopaedics, Government Royapettah Hospital, Chennai, Tamil Nadu, India,, Muthu Sathish ,   [4] Orthopaedic Research Group, Coimbatore, Tamil Nadu, India, [5] Department of Biotechnology, Faculty of Engineering, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India, [6] Department of Orthopaedics, Government Medical College, Karur, Tamil Nadu, India.
Published: January 2024

Introduction: Aneurysmal bone cyst (ABC) is a benign expansile osteolytic lesion, characterized by a blood-filled cavity in the bone. Giant ABC (GABC) is an uncommon condition due to the delayed presentation of an ABC that is difficult to handle when it occurs in long weight-bearing bones due to its aggressive nature. The common treatment relies on total resection of tumor with reconstruction of the resultant defect. Case Report: We present the results of 5 cases of GABCs of long bones managed with non-vascularized fibular graft in a cross-beam fashion along with internal fixation. All patients achieved complete consolidation of the lesion by 12 months along with full incorporation of the graft with good-excellent musculoskeletal tumor society scores. None of the patients had recurrence/pathological fracture till 2 years of follow-up. Conclusion: We suggest the method of using a non-vascularized fibula graft in a cross-beam fashion to reconstruct the void from the resection of long-bone GABC as a safe, reliable technique with excellent functional and radiological results. Keywords: Giant Aneurysmal Bone Cyst, Fibular Graft, Resection, Recurrence, Reconstruction
Unilateral Biportal Endoscopic Approach for Symptomatic Adjacent Segment Disease: Case Report and Technical Note
Authors:   Department of Spine Surgery, Yonsei Okay Hospital, Seoul, South Korea., Sakhrekar Rajendra , Ha Ji Soo ,   Department of Spine Surgery, Yonsei Okay Hospital, Seoul, South Korea., Don Hee- ,   Department of Spine Surgery, Yonsei Okay Hospital, Seoul, South Korea., Kim Do-Hyoung ,   Department of Spine Surgery, Yonsei Okay Hospital, Seoul, South Korea., Kim Chang Wook ,   Department of Spine Surgery, Yonsei Okay Hospital, Seoul, South Korea., Kulkarni Shreenidhi ,   Department of Spine Surgery, Yonsei Okay Hospital, Seoul, South Korea.
Published: January 2024

Introduction: Recently, lumbar degenerative disease has been treated using unilateral biportal endoscopic (UBE) lumbar interbody fusion. However, the use of the UBE approach for symptomatic ASD following lumbar interbody fusion surgery isn’t illustrated widely in the literature. This case report and technical note describe the use of the UBE approach for symptomatic ASD. Case Report: A 72-year-old female who underwent conventional fusion surgery elsewhere twelve years ago at the L5-S1 level presented with severe back pain (VAS 8/10) and radicular pain in both legs (left > right) (left VAS 7/10, right VAS 7/10) for 1 year with an ODI score of 70%. Preoperative X-ray and MRI showed dynamic instability with spondylolisthesis at L4–5. We performed an upper-level extension using UBE FES techniques to resolve ASD. The operative time was 132 minutes, blood loss was 40 ml. After surgery, the patient was followed up at 1 week, 6 weeks, 3 months, 6 months, 12 months, and 2 years. The pain and tingling sensation in the legs got better at the 1-week follow-up itself with a VAS score of 0/10 and an ODI score of 10% at the 2-year follow-up. Patient satisfaction was surveyed using Odom’s criteria at each follow-up visit (at 1 week, 6 weeks,3 months, 6 months, and 2 years) and found to be excellent. Postoperative imaging showed a good reduction and canal decompression at L4–5. Conclusion: The UBE fusion extension technique for ASD is a safe, less invasive, and effective treatment option for lumbar interbody fusion extension and posterior pedicle screw revision with less morbidity and early recovery. Keywords: Unilateral Biportal Endoscopic, Adjacent Segment Disease, Case Report, Technical Note
100G FSO field trial with transmitter power adaptability using a LoRa feedback channel
Authors: Brandão Bruno T. , Fernandes Marco A. , Fernandes Gil M. , Kaai Nourdin , Tomeeva Alina , van Der Wielen Bas , Reid John , Raiteri Daniele , Guiomar Fernando P. , Monteiro Paulo P.
Published: January 2024

The popularity of free-space optics (FSO) communications is rising as a key enabler for widespread communications since it can provide fiber-like connectivity to regions where fiber deployment is not feasible and radio-frequency (RF) technologies cannot comply with the bandwidth requirements. However, the reliability of FSO links is severely affected by fluctuations in the received optical power caused by weather instability, atmospheric turbulence, and pointing errors. In this work, we propose an adaptive power pre-compensation system enabled by a low-cost, long-range (LoRa) RF feedback link. We experimentally demonstrate this system in a 1.8 km field trial supporting 100 Gbps coherent FSO transmission under approximately 10 dB of slow-fading over a 16 h period. Our results show a considerable reduction of up to 5 dB in the average dynamic range of the receiver and substantial improvement in the link reliability (7% on average) when compared with an estimated fixed power transmission. Further reliability or data-rate improvements can also be achieved with joint optimization of the FEC overhead and the adaptive power transmission scheme.
A tailless FBG smart bolt with excellent performance
Authors: Li Xiaojin , Zheng Min , Hou Dan , yang zhimin , li run
Published: January 2024

The existing smart bolts based on fiber Bragg grating (FBG) have limitations, such as with long tail fibers and without satisfactory repeatability (R-squared value < 0.990), these limit their further application. Here, a tailless FBG smart bolt with excellent repeatability (R-squared value ≥ 0.999) that can simultaneously measure the strain and temperature through the design of the integrated FBG sensor is developed. A theoretical approach is employed to derive the linear relationship between the applied torque and the central wavelength of the tailless FBG smart bolt. The integrated FBG sensor embedded in the tailless FBG smart bolt, includes the temperature compensated FBG and strain measured FBG. In addition, a nominal strength of M24 bolt is redesigned. To enable the experimental study, the tailless FBG smart bolt is designed, fabricated and tested. Experimental results reveal the good linear relationship between the applied torque and the central wavelength of the integrated FBG sensor, which demonstrate that this tailless FBG smart bolt is suitable for the axial forces monitoring and the bolt looseness monitoring.
H3K27me3 is vital for fungal development and secondary metabolite gene silencing, and substitutes for the loss of H3K9me3 in the plant pathogen Fusarium proliferatum
Authors: Studt-Reinhold Lena , Atanasoff-Kardjalieff Anna K. , Berger Harald , Petersen Celine , Bachleitner Simone , Sulyok Michael , Fischle Alica , Humpf Hans-Ulrich , Kalinina Svetlana , Søndergaard Teis Esben
Published: January 2024

Facultative heterochromatin marked by histone H3 lysine 27 trimethylation (H3K27me3) is an important regulatory layer involved in secondary metabolite (SM) gene silencing and crucial for fungal development in the genus Fusarium. While this histone mark is essential in some (e.g., the rice pathogen Fusarium fujikuroi), it appears dispensable in other fusaria. Here, we show that deletion of FpKMT6 is detrimental but not lethal in the plant pathogen Fusarium proliferatum, a member of the Fusarium fujikuroi species complex (FFSC). Loss of FpKmt6 results in aberrant growth, and expression of a large set of previously H3K27me3-silenced genes is accompanied by increased H3K27 acetylation (H3K27ac) and an altered H3K36me3 pattern. Next, H3K9me3 patterns are affected in Δfpkmt6, indicating crosstalk between both heterochromatic marks that became even more obvious in a strain deleted for FpKMT1 encoding the H3K9-specific histone methyltransferase. In Δfpkmt1, all H3K9me3 marks present in the wild-type strain are replaced by H3K27me3, a finding that may explain the subtle phenotype of the Δfpkmt1 strain which stands in marked contrast to other filamentous fungi. A large proportion of SM-encoding genes is allocated with H3K27me3 in the wild-type strain and loss of H3K27me3 results in elevated expression of 49% of them. Interestingly, genes involved in the biosynthesis of the phytohormones gibberellins (GA) are among the most upregulated genes in Δfpkmt6. Although several FFSC members harbor GA biosynthetic genes, its production is largely restricted to F. fujikuroi, possibly outlining the distinct lifestyles of these notorious plant pathogens. We show that H3K27me3 is involved in GA gene silencing in F. proliferatum and at least one additional FFSC member, and thus, may serve as a regulatory layer for gene silencing under non-favoring conditions.
Induced pluripotent stem cell-derived human macrophages as an infection model for Leishmania donovani
Authors: Baert Lore , Rudy Serena , Pellisson Mélanie , Doll Thierry , Rocchetti Romina , Kaiser Marcel , Mäser Pascal , Müller Matthias
Published: January 2024

The parasite Leishmania donovani is one of the species causing visceral leishmaniasis in humans, a deadly infection claiming up to 40,000 lives each year. The current drugs for leishmaniasis treatment have severe drawbacks and there is an urgent need to find new anti-leishmanial compounds. However, the search for drug candidates is complicated by the intracellular lifestyle of Leishmania. Here, we investigate the use of human induced pluripotent stem cell (iPS)-derived macrophages (iMACs) as host cells for L. donovani. iMACs obtained through embryoid body differentiation were infected with L. donovani promastigotes, and high-content imaging techniques were used to optimize the iMACs seeding density and multiplicity of infection, allowing us to reach infection rates up to 70% five days after infection. IC50 values obtained for miltefosine and amphotericin B using the infected iMACs or mouse peritoneal macrophages as host cells were comparable and in agreement with the literature, showing the potential of iMACs as an infection model for drug screening.
Snakebite prevalence and risk factors in a nomadic population in Samburu County, Kenya: A community-based survey
Authors: Tianyi Frank-Leonel , Oluoch George O. , Otundo Denis , Ofwete Robert , Ngari Cecilia , Trelfa Anna , Ahmed Sayem , Wang Duolao , Smith Monica , Meta Viviane , Casewell Nicholas R. , Lalloo David G. , Harrison Robert A. , Stienstra Ymkje
Published: January 2024

Introduction

Snakebite is an important public health concern, especially in tropical areas, but the true burden remains unclear due to sub-optimal reporting and over-reliance on health facility-based data.

Methods

A community-based cross-sectional survey was conducted in Samburu County, Kenya from December 2019 to March 2020. Geospatial techniques were used to create a sampling frame of all households in Samburu County and a multistage cluster sampling strategy to select households and recruit study participants. Five year prevalence and mortality rates were estimated, the characteristics and circumstances of snakebite were described, and multilevel logistic regression models were built to identify independent risk factors for snakebite.

Results

We recruited 3,610 individuals living in 875 households from 30 clusters. The 5-year prevalence of snakebite was 2.2% (95% CI 1.4%–3.4%), and the 5-year mortality rate was 138 (95% CI 44–322) deaths per 100,000 inhabitants, resulting in an estimated 1,406 snakebites and 88 deaths from snakebites per year in Samburu County. Snakebite incidents often occurred at night between 9pm and 6 am (44%, n = 36), and the participants were mostly walking/playing outdoors (51%, n = 41) or sleeping (32%, n = 27) when they were bitten. Lower household socioeconomic status and smaller numbers of people per house were significant independent risk factors.

Conclusion

Samburu County has a high snakebite burden and the most victims are bitten while sleeping or walking outdoors at night. Snakebite prevention and health promotion programs in Samburu County, and other endemic regions, need to be contextualised and consider the geographic, seasonal, and temporal specificities found in our study. Our findings also have implications for health care delivery, especially identification of the need for night-time staffing with expertise in snakebite management and antivenom availability to better manage patients and thereby improve outcomes.
The nutritional status of mycetoma affected patients seen at the Mycetoma Research Center, Sudan
Authors: Gabani Manal Hassan , Ahmed Arwa Abdelraouf , Hassan Alshaima Abdelelah , Abdalla Mona Abdelrahim , Mustafa Samar Abdelmahmoud , Alobaid Tasneem Abdelmutalab , Khatir Abrar Adam , Mohammed Reell Mukhlis , Awad Nehal Ibrahim , Abdellateef Tanzeel Alqurashi , Hassan Abeer , Ahmed Eiman Siddig , Ali Mohammed Zain , Fahal Ahmed Hassan
Published: January 2024

Nutrition plays a critical and crucial role in addressing neglected tropical diseases (NTDs) and their complications, as they often contribute to malnutrition, which can worsen the impact of these conditions. Therefore, it is necessary to investigate the nutritional status of mycetoma patients, which has not been explored previously.

This descriptive cross-sectional hospital-based study was conducted at the Mycetoma Research Center (MRC), University of Khartoum, Sudan. The study included 179 confirmed mycetoma patients and an equal number of age- and sex-matched normal controls. The nutritional status of the mycetoma patients was assessed and compared with that of the control group. The majority of the patients were young adults with varying educational levels, predominantly from Central Sudan. The foot was the most commonly affected part; most patients had lesions more than 10 cm in diameter.

The Body Mass Index (BMI) was calculated for both study groups, revealing that 43.5% of the patients and 53.6% of controls had a normal BMI. Furthermore, 36% of patients were underweight, contrasting with only 11% in the control group. Correlation analyses indicated no significant associations between BMI and age groups, educational levels, daily meals, food quantity, and appetite in the study population (p > 0.05). Similarly, no significant differences were observed in BMI concerning disease duration and affected sites (p = 0.0577). The Kruskal-Wallis test did not reveal significant differences in BMI means among the groups.

The study revealed that most participants consumed three meals daily, and the control group showed a more robust appetite and consumed more food than the patient group (p = 0.005). Nevertheless, there were no significant differences in the consumption of different food types between the patient and control groups and among different BMI categories (p = 0.025 and 0.040, respectively).
The role of naturally acquired intracellular Pseudomonas aeruginosa in the development of Acanthamoeba keratitis in an animal model
Authors: Rayamajhee Binod , Willcox Mark , Henriquez Fiona L. , Vijay Ajay Kumar , Petsoglou Constantinos , Shrestha Gauri Shankar , Peguda Hari Kumar , Carnt Nicole
Published: January 2024

Background

Acanthamoeba is an environmental host for various microorganisms. Acanthamoeba is also becoming an increasingly important pathogen as a cause of keratitis. In Acanthamoeba keratitis (AK), coinfections involving pathogenic bacteria have been reported, potentially attributed to the carriage of microbes by Acanthamoeba. This study assessed the presence of intracellular bacteria in Acanthamoeba species recovered from domestic tap water and corneas of two different AK patients and examined the impact of naturally occurring intracellular bacteria within Acanthamoeba on the severity of corneal infections in rats.

Methodology/Principal findings

Household water and corneal swabs were collected from AK patients. Acanthamoeba strains and genotypes were confirmed by sequencing. Acanthamoeba isolates were assessed for the presence of intracellular bacteria using sequencing, fluorescence in situ hybridization (FISH), and electron microscopy. The viability of the bacteria in Acanthamoeba was assessed by labelling with alkyne–functionalized D–alanine (alkDala). Primary human macrophages were used to compare the intracellular survival and replication of the endosymbiotic Pseudomonas aeruginosa and a wild type strain. Eyes of rats were challenged intrastromally with Acanthamoeba containing or devoid of P. aeruginosa and evaluated for the clinical response. Domestic water and corneal swabs were positive for Acanthamoeba. Both strains belonged to genotype T4F. One of the Acanthamoeba isolates harboured P. aeruginosa which was seen throughout the Acanthamoeba’s cytoplasm. It was metabolically active and could be seen undergoing binary fission. This motile strain was able to replicate in macrophage to a greater degree than strain PAO1 (p<0.05). Inoculation of Acanthamoeba containing the intracellular P. aeruginosa in rats eyes resulted in a severe keratitis with increased neutrophil response. Acanthamoeba alone induced milder keratitis.

Conclusions/Significance

Our findings indicate the presence of live intracellular bacteria in Acanthamoeba can increase the severity of acute keratitis in vivo. As P. aeruginosa is a common cause of keratitis, this may indicate the potential for these intracellular bacteria in Acanthamoeba to lead to severe polymicrobial keratitis.
Bilateral trade potential analysis of the Lanzhou-Kathmandu South Asian rail-road freight trains linking China and Nepal: A stochastic frontier gravity model approach
Authors: Tian Fei
Published: January 2024

In this paper, the stochastic frontier gravity model is applied to analyze the trade potential between China and Nepal and the prospects of Lanzhou-Kathmandu South Asian rail-road freight trains (LKSARFT). Based on the statistical data, we test the Exports Efficiency (EE), Bilateral Trade Efficiency (BTE), Exports Trade Potential (ETP), Bilateral Trade Potential (BTP), Extended Exports Trade Potential (EETP), Extended Bilateral Trade Potential (EBTP), Improved Exports Trade Potential (IETP) and Improved Bilateral Trade Potential (IBTP) between China and Nepal, the following analysis results can be found: for the bilateral trade model, the bilateral non-efficiency factor decreasing at a rate of 0.057 with time increasing, bilateral trade increasing at a rate of 0.057 with time increasing. For the exports model, the exports non-efficiency factor increasing at a rate of 0.004 with time increasing, exports trade decreasing at a rate of 0.057 with time increasing. The BTE between China and Nepal increases when time changes, the EE from China to Nepal remains constant changing during the 18 years. The changing range of BTE is 0.002–0.05; the changing range of EE from China to Nepal is over 0.1, larger than the BTE. The BTE and EE ranking among the eight South Asian countries are ranking fifth and fourth during the 18 years. exports trade resistance from China to Nepal is larger than bilateral trade resistance; The import trade potential from Nepal to China is huge, the focus of bilateral trade between China and Nepal may be changed, there are more goods may be exported from Nepal to China, and China may become trade deficit when trading with Nepal. Then, the development bottlenecks of the LKSARFT are analyzed. Finally, we give policy directions to boost bilateral trade efficiency and tap the potential of bilateral trade between China and Nepal.
Predication of the post mining land use based on random forest and DBSCAN
Authors: Bo Qiang , Lv Pinhan , Wang Ziguan , Wang Qian , Li Zechuan
Published: January 2024

Mine reclamation is one of the most important stages of the mining activities in line with the basic principles of sustainable development. In this study, different post-mining land uses are evaluated in the Hongliulin mining area, which is located in Shen mu country of China. 145 soil samples were collected in the May,2021 by using the soil auger, and the sampling depths were 0–20 cm. The sampling points contains 45 to be reclaimed samples and 100 existing classification land use types. 14 environmental factors including soil organic matter (SOM), total nitrogen (TN), available phosphate (AP), available potassium (AK), K, Slope steepness, curvatures, aspect, length, Topographic Wetness Index (TWI), NDVI and elevation were extracted and calculated based on laboratory test and digital elevation map. The random forest classier showed a great prediction capability, with only 1 miss-classified sample in the validation data-set, the accuracy of the classification model was 95%. The content of TN of C1 is 5 times more than C2 and 4 times more than C3. Also, the K value of C1 column is maximum and over 0.4, which means the soil particle is relatively smaller and the soil texture of it is sandy loam. In terms of the 45 to be reclaimed samples, 15 samples were classified into C1, 23 samples were classified into C2, 5 samples were classified into C3, 2 samples were classified into C4. The value of K and content of soil nutrients of the samples classified to be C1 column(C1-C) is maximum. The soybean and murphy were suggested based on the soil nutrients index and with the mining disturbance on cluster 2 of C1, the ground subsidence filling as well as soil nutrients increased strategy should be applied. The result may contribute to the land use planning and idle land utilization strategy.
Living on the edge: Crayfish as drivers to anoxification of their own shelter microenvironment
Authors: Neculae Adrian , Barnett Zanethia C. , Miok Kristian , Dalosto Marcelo M. , Kuklina Iryna , Kawai Tadashi , Santos Sandro , Furse James M. , Sîrbu Ovidiu I. , Stoeckel James A. , Pârvulescu Lucian
Published: January 2024

Burrowing is a common trait among crayfish thought to help species deal with adverse environmental challenges. However, little is known about the microhabitat ecology of crayfish taxa in relation to their burrows. To fill this knowledge gap, we assessed the availability of oxygen inside the crayfish shelter by series of in-vivo and in-silico modelling experiments. Under modeled condition, we found that, except for the entrance region of the 200 mm, a flooded burrow microenvironment became anoxic within 8 h, on average. Multiple 12-hour day-night cycles, with burrows occupied by crayfish for 12 h and empty for 12 h, were not sufficient for refreshing the burrow microenvironment. We then examined the degree to which crayfish species with different propensities for burrowing are tolerant of self-created anoxia. From these experiments, primary and secondary burrowers showed best and most consistent tolerance—exhibiting ≥ 64% survival to anoxia and 25–91% survival of ≥ 9 h at anoxia, respectively. Tertiary burrowers exhibited little to no tolerance of anoxia with 0–50% survival to anoxia and only one species exhibiting survival (2%) of ≥ 9 h at anoxia. Results suggest that moderate to strongly burrowing crayfish can quickly draw down the dissolved oxygen in burrow water but appear to have conserved a legacy of strong tolerance of anoxia from their monophyletic ancestors–the lobsters–whereas tertiary burrowers have lost (or never evolved) this ability.