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Introduction Haglund's deformity is an abnormal bony postero-superior calcaneal prominence which causes the posterior heel pain. Surgery is the choice of treatment after failed conservative management. Both open and endoscopic techniques are used to treat this condition. In this article, we discuss endoscopic calcaneoplasty for the management of such cases. Methods All included patients underwent bi-portal endoscopic calcaneoplasty. Clinical outcomes were assessed by using the visual analog scale (VAS) score and the American Orthopaedic Foot and Ankle Society (AOFAS) score. The radiological outcome was assessed by a change in the Fowler-Philip angle (FPA). All patients were followed at one month, three months, and six months postoperatively. Results A total of 22 patients were included in this prospective study. Patients were followed up to six months postoperatively. The mean VAS score was 6.32 ± 0.65 which was significantly reduced to 0.91 ± 0.68 (p < 0.001) at six months. Similarly, AOFAS Score was improved to 90.01 ± 2.67 (p < 0.001) from 64.36 ± 7.07 preoperatively. The mean Fowler Philip Angle was reduced from 72.45° ± 3.74° to 65.77° ± 2.25° at six months (p < 0.001). Conclusion Bi-portal endoscopic calcaneoplasty significantly improves clinical outcomes in Haglund's deformity. Compared to open procedures, bi-portal endoscopic calcaneoplasty offers several advantages, including shorter recovery times, smaller incisions, and better clinical results for Haglund's deformity.
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Bulk wave acoustic time-of-flight (ToF) measurements in pipes and closed containers can be hindered by guided waves with similar arrival times propagating in the container wall, especially when a low excitation frequency is used to mitigate sound attenuation from the material. Convolutional neural networks (CNNs) have emerged as a new paradigm for obtaining accurate ToF in non-destructive evaluation (NDE) and have been demonstrated for such complicated conditions. However, the generalizability of ToF-CNNs has not been investigated. In this work, we analyze the generalizability of the ToF-CNN for broader applications, given limited training data. We first investigate the CNN performance with respect to training dataset size and different training data and test data parameters (container dimensions and material properties). Furthermore, we perform a series of tests to understand the distribution of data parameters that need to be incorporated in training for enhanced model generalizability. This is investigated by training the model on a set of small- and large-container datasets regardless of the test data. We observe that the quantity of data partitioned for training must be of a good representation of the entire sets and sufficient to span through the input space. The result of the network also shows that the learning model with the training data on small containers delivers a sufficiently stable result on different feature interactions compared to the learning model with the training data on large containers. To check the robustness of the model, we tested the trained model to predict the ToF of different sound speed mediums, which shows excellent accuracy. Furthermore, to mimic real experimental scenarios, data are augmented by adding noise. We envision that the proposed approach will extend the applications of CNNs for ToF prediction in a broader range.
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Bidirectional oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalysts are crucial for renewable energy transduction via electrolyzers and fuel cell. Here, we present a protocol for harnessing the cobalt complex for bidirectional O2/H2O transformation in neutral water via electrocatalysis/photocatalysis. We describe steps for monitoring ORR and OER in neutral aqueous solution, measuring O2 concentration, and identifying the probable catalytic mechanism for ORR and OER. We then detail procedures for examining catalyst behavior under photocatalytic conditions in neutral aqueous surroundings. For complete details on the use and execution of this protocol, please refer to Saini et al.1.
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Cobalto , Oxidación-Reducción , Oxígeno , Agua , Catálisis , Cobalto/química , Agua/química , Oxígeno/química , Procesos Fotoquímicos , Técnicas Electroquímicas/métodos , Complejos de Coordinación/químicaRESUMEN
Bacterial infections are rising, and antimicrobial resistance (AMR) in bacteria has worsened the scenario, requiring extensive research to find alternative therapeutic agents. Terpenoids play an essential role in protecting plants from herbivores and pathogens. The present study was designed to focus on in silico evaluation of terpenoids for their affinity towards two necessary enzymes, i.e. DHFR and DHPS, which are involved in forming 5, 6, 7, 8-tetrahydrofolate, a key component in bacterial DNA synthesis proteins. Additionally, to account for activity against resistant bacteria, their affinity towards the L28R mutant of DHFR was also assessed in the study. The structure-based drug design approach was used to screen the compound library of terpenes for their interaction with active sites of DHFR and DHPS. Further, compounds were screened based on their dock score, pharmacokinetic properties, and binding affinities. A total of five compounds for each target protein were screened, having dock scores better than their respective standard drug molecules. CNP0169378 (-8.4 kcal/mol) and CNP0309455 (-6.5 kcal/mol) have been identified as molecules with a higher affinity toward the targets of DHFR and DHPS, respectively. At the same time, one molecule CNP0298407 (-5.8 kcal/mol for DHPS, -7.6 kcal/mol for DHFR, -6.1 kcal/mol for the L28R variant), has affinity for both proteins (6XG5 and 6XG4). All the molecules have good pharmacokinetic properties. We further validated the docking study by binding free energy calculations using the MM/GBSA approach and molecular dynamics simulations.Communicated by Ramaswamy H. Sarma.
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Antimaláricos , Antagonistas del Ácido Fólico , Antimaláricos/farmacología , Pirimetamina , Antagonistas del Ácido Fólico/farmacología , Sulfadoxina/farmacología , Sulfadoxina/uso terapéutico , Simulación de Dinámica Molecular , Dihidropteroato Sintasa/genética , Terpenos/farmacología , Plasmodium falciparum , Tetrahidrofolato Deshidrogenasa/genéticaRESUMEN
The O2/H2O redox couple is vital in various renewable energy conversion strategies. This work delves into the Co(L-histidine)2 complex, a functional mimic of oxygen-carrying metalloproteins, and its electrochemical behavior driving the bidirectional oxygen reduction (ORR) and oxygen evolution (OER) activity in neutral water. This complex electrocatalyzes O2 via two distinct pathways: a two-electron O2/H2O2 reduction (catalytic rate = 250 s-1) and a four-electron O2 to H2O production (catalytic rate = 66 s-1). The formation of the key trans-µ-1,2-Co(III)-peroxo intermediate expedites this process. Additionally, this complex effectively oxidizes water to O2 (catalytic rate = 15606 s-1) at anodic potentials via a Co(IV)-oxo species. Additionally, this complex executes the ORR and OER under photocatalytic conditions in neutral water in the presence of appropriate photosensitizer (Eosin-Y) and redox mediators (triethanolamine/ORR and Na2S2O8/OER) at an appreciable rate. These results highlight one of the early examples of both electro- and photoactive bidirectional ORR/OER catalysts operational in neutral water.
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The presence of efficient energy storage and conversion technologies is essential for the future energy infrastructure. Here, we describe crafting a heterostructure composed of a suitably interlinked CeO2 and polycrystalline Bi2O3 dopant prepared on a reduced graphene oxide (Ce_Bi2O3@rGO) surface. This material exhibits exceptional electrocatalytic hydrogen and oxygen evolution reaction in alkaline water (pHâ¼14.0) to trigger the full water-splitting cycle as a Janus catalyst. The stepwise catalyst preparation and electrochemical cell assembly for simultaneous hydrogen and oxygen evolution have been narrated. For complete details on the use and execution of this protocol, please refer to Aziz et al. (2022).1.
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Hidrógeno , Oxígeno , Ciclo Celular , AguaAsunto(s)
Misoprostol , Oxitócicos , Embarazo , Femenino , Humanos , Maduración Cervical , Trabajo de Parto InducidoRESUMEN
Lignin@Fe3O4 nanoparticles adsorb at oil-water interfaces, form Pickering emulsions, induce on-demand magnetic responses to break emulsions, and can sequester oil from water. Lignin@Fe3O4 nanoparticles were prepared using a pH-induced precipitation method and were fully characterized. These were used to prepare Pickering emulsions with castor oil/Sudan red G dye and water at various oil/water volume ratios and nanoparticle concentrations. The stability and demulsification of the emulsions under different magnetic fields generated with permanent magnets (0-540 mT) were investigated using microscopy images and by visual inspection over time. The results showed that the Pickering emulsions were more stable at the castor oil/water ratio of 50/50 and above. Increasing the concentration of lignin@Fe3O4 improved the emulsion stability and demulsification rates with 540 mT applied magnetic field strength. The adsorption of lignin@Fe3O4 nanoparticles at the oil/water interface using 1-pentanol evaporation through Marangoni effects was demonstrated, and magnetic manipulation of a lignin@Fe3O4 stabilized castor oil spill in water was shown. Nanoparticle concentration and applied magnetic field strengths were analyzed for the recovery of spilled oil from water; it was observed that increasing the magnetic strength increased oil spill motion for a lignin@Fe3O4 concentration of up to 0.8 mg mL-1 at 540 mT. Overall, this study demonstrates the potential of lignin-magnetite nanocomposites for rapid on-demand magnetic responses to externally induced stimuli.
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Developing a robust, cost-effective, and user-friendly sensor for monitoring molecular oxygen (O2) ranging from a minute to a medically relevant level (85-100%) in a stream of flowing breathable gas is vital in various industrial domains. Here, we report an innovative application of the cobalt(l-histidine)2 complex, a bioinspired model of O2-carrying metalloproteins, for rapid and reliable sensing of O2 from 0 to 100% saturation levels under realistic conditions. We have established two distinct colorimetric O2 detection techniques, which can be executed with the use of a common smartphone camera and readily available color-detecting software. A series of spectroscopic experiments were performed to demonstrate the molecular-level alteration in cobalt(l-histidine)2 following its exposure to oxygen, leading to an exclusive pink-to-brown color change. Therefore, this study establishes a template for designing bioinspired molecular complexes for O2 sensing, leading to practical and straightforward solutions. This metal-amino acid complex's broad-spectrum sensing of O2 has widened the scope of bioinspired model complexes for divergent applications in industrial sectors.
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Ultrasonic linear arrays have great potential to generate high-quality three-dimensional (3D) images by scanning the array. However, the generated images suffer from low resolution in the elevation plane, limiting the image quality for a reliable 3D Non-Destructive Testing (NDT) inspection. Although several ultrasonic imaging methods have been implemented to inspect different types of defects, there has been limited research to characterise surface-breaking cracks (SBCs) in 3D quantitatively. To improve the characterisation of surface-breaking cracks (SBCs), a 3D hybrid imaging method is proposed by combining the Half Skip Total Focusing Method (HSTFM) and the Synthetic Aperture Focusing Technique (SAFT) using a linear array. This paper proposed the implementation of an array with a reduced element length for full matrix capture (FMC) data acquisition. In conjunction with the hybrid imaging method, a reduced element array enables the utilisation of the information from a broad ultrasonic beam in the elevation direction to achieve improved image resolution. The imaging capability is assessed via a point spread function (PSF) as well as numerical simulations. From the PSF measurements, the image resolution is shown to improve with the smaller element length of the array, which is attributable to the combination of wide beamwidth and hybrid imaging method. Thereafter, experimental validation was performed with arrays of different elevation lengths, where an excellent match with the numerical results was observed. Furthermore, the crack sizing was performed using a 6-dB-drop rule, which assisted in accurately predicting the shape and size of the SBCs and is shown to measure the depth of SBCs with greater confidence. It is shown that a reduced array elevation with the hybrid imaging method and sizing method yields improved image resolution contrary to conventional linear arrays. This approach can offer a significant improvement in manifesting complete comprehension of the spatial defect relationship, enabling NDT engineers to analyse the inspection results quantitatively in 3D for progressive reliability.
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Background: The requirement for the mutation analysis for Kirsten rat sarcoma viral oncogene (KRAS) in colorectal cancer (CRC) is rapidly increasing as it is a predictive biomarker and also, its absence signifies response to anti-epidermal growth factor receptor (anti-EGFR) antibody treatment. The aim of our study was to investigate the pathological diagnosis and distribution of KRAS mutations in colorectal cancer with the use of next generation sequencing platform (Ion Torrent). Methods: A total of 56 CRC samples were tested to identify the genetic mutations, especially KRAS using the primers which included ~2800 COSMIC mutations of 50 oncogenes. Ion Torrent personal genome machine (semiconductor-based sequencing) was used for the sequencing and analysis. Along with KRAS, other 49 genes were also studied for COSMIC mutations. Results: KRAS mutation 25 (44.6%) had the highest frequency, followed by TP53 10 (17.9%) and PIK3CA mutation 4 (7.1%). Of all the KRAS mutations identified, mutations in codon 12 were most frequent followed by mutations in codon 13 and 61. The most frequent substitution was glycine to aspartate mutation in codon 12 (p.Gly12Asp) followed by glycine to valine (p.Gly12Val). Combinations of mutations were also studied. Our study revealed that seven cases (12.5%) had both KRAS and TP53 mutations (highest of all the combinations). Conclusion: The analysis of KRAS mutation frequency and its mutational subtype analysis in human CRCs by using semiconductor-based platform in routine clinical practices have been performed in Indian population. The findings were similar to earlier published reports from the Western literature.
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Neoplasias Colorrectales , Secuenciación de Nucleótidos de Alto Rendimiento , Codón , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Glicina/genética , Humanos , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genéticaRESUMEN
INTRODUCTION: Solid organ transplantation is the preferred therapeutic modality of treatment in patients affected by terminal organ failures. Human leukocyte antigens (HLAs) plays an important role in graft survival. In many of the cases of rejection, antibodies are directed against HLA antigens expressed on the cells of the transplanted organ. Pre-transplant compatibility testing involves the use of different methodologies for the determination of anti-HLA antibodies. Luminex single-antigen bead (SAB) assay demonstrates higher sensitivity and specificity in detecting anti-HLA antibodies. The aim of this study was to determine the prevalence of anti-HLA antibodies in pre-transplant work up recipients, planned for renal transplant at a tertiary care center in India. METHODS: 1640 patients visiting tertiary care hospital for pre-transplant compatibility testing were screened with complement-dependent micro-lymphocytotoxicity crossmatch (CDC-XM) and flow cytometric crossmatch (FC-XM). The patients positive for either or both screening tests were assayed with the Luminex SAB tests in order to establish defined antigen specificity of the alloantibodies and determining donor-specific antibody (DSA). RESULTS: The two most frequent antibodies identified in each A, B, C locus of HLA class I were -A*24:03 (43.9%), A*25:01 (36.6%), B*57:01 (40.3%), B*15:12 (37.1%), C*17:01 (61.9%), C*07:01 (52.4%) and in DR, DQ DP locus in HLA class II were DRB1*09:01(40.0%), DRB1*14:04(37.6%), DQA1*04:01/DQB1*03:03 (58.4%), DQA1*05:01/DQB1*03:01 (55.1%), DPA1*02:01/DPB1*17:01 (55.0%), DPA1*02:01/DPB1*05:01 (45.0%). CONCLUSION: This study has found the prevalence and specificity of anti-HLA antibodies in north India.
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Fluorescent chemical probes have become powerful tools to study biological events in living cells. They provide a great opportunity to quantitatively and qualitatively analyze the physiological and biochemical properties of living cells in real time. The ability of researchers to manipulate these probes for a desired specific purpose has turned many heads in the scientific community. Despite a slow start, fluorescent probe research has seen exponential growth over the last decade in the world. This change required some adventurous and creative scientists from different fields-like biology, medicine, and chemistry-to come together to facilitate the constant expansion of this field. This review article introduces some fundamental concepts related to fluorescent probe designing and development. It also summarizes various fluorescent probes with superior optical properties used in fields like cell biology, cellular imaging, medical research, and cancer diagnosis. It is hoped that this article will encourage more young and creative scientists to contribute their talents to this field.
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Colorantes Fluorescentes/química , Células Madre Pluripotentes Inducidas/citología , Neoplasias/diagnóstico por imagen , Neuronas/citología , Imagen Óptica , Colorantes Fluorescentes/síntesis química , HumanosRESUMEN
Magnetic nanoparticles (MNPs) were synthesized using the colloidal co-precipitation method and further coated with silica using the Stöber process. These were functionalized with carboxylic and amine functionalities for further covalent immobilization of antibodies on these MNPs. The procedure for covalent immobilization of antibodies on MNPs was developed using 1-ethyl-3-(dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The evaluation of the efficiency of the coupling reaction was carried out by UV-vis spectrophotometry. The developed antibodies coupled to MNPs were tested for the pre-concentration of two biomarkers tumor necrosis factor alpha (TNF-α) and Interleukin-10 (IL-10). Both biomarkers were assessed in the matrix based on phosphate-buffered saline solution (PBS) and artificial saliva (AS) to carry out the demonstration of the format assay. Supernatants were used to determine the number of free biomarkers for both studies. Reduction of the nonspecific saliva protein adsorption on the surface of the complex antibodies-MNPs to levels low enough to allow the detection of biomarkers in complex media has been achieved.
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Biomarcadores , Técnicas Biosensibles , Nanopartículas de Magnetita/química , Saliva Artificial/análisis , Humanos , Nanopartículas de Magnetita/ultraestructura , Modelos Teóricos , Estructura Molecular , Tamaño de la PartículaRESUMEN
By minor structure modification of spherical carborane ligands, in a similar synthetic procedure, large morphological changes are produced in Quantum Nanocrystals (QNCs). The spheres are icosahedral C2B10H12 molecules with binding sites on the carbon, and the QNCs produced are Quantum Dots, Rods, Rings and Tetrapods. These QNCs demonstrated high stability and impeccable emissive properties for more than a year.
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Cancer stem cells (CSCs) are believed to exhibit distinctive self-renewal, proliferation, and differentiation capabilities, and thus play a significant role in various aspects of cancer. CSCs have significant impacts on the progression of tumors, drug resistance, recurrence and metastasis in different types of malignancies. Due to their primary role, most researchers have focused on developing anti-CSC therapeutic strategies, and tremendous efforts have been put to explore methods for selective eradication of these therapeutically resistant CSCs. In recent years, many reports have shown the use of CSCs-specific approaches such as ATP-binding cassette (ABC) transporters, blockade of self-renewal and survival of CSCs, CSCs surface markers targeted drugs delivery and eradication of the tumor microenvironment. Also, various therapeutic agents such as small molecule drugs, nucleic acids, and antibodies are said to destroy CSCs selectively. Targeted drug delivery holds the key to the success of most of the anti-CSCs based drugs/therapies. The convention CSCs-specific therapeutic agents, suffer from various problems. For instance, limited water solubility, small circulation time and inconsistent stability of conventional therapeutic agents have significantly limited their efficacy. Recent advancement in the drug delivery technology has demonstrated that specially designed nanocarrier-based drug delivery approaches (nanomedicine) can be useful in delivering sufficient amount of drug molecules even in the most interiors of CSCs niches and thus can overcome the limitations associated with the conventional free drug delivery methods. The nanomedicine has also been promising in designing effective therapeutic regime against pump-mediated drug resistance (ATP-driven) and reduces detrimental effects on normal stem cells. Here we focus on the biological processes regulating CSCs' drug resistance and various strategies developed so far to deal with them. We also review the various nanomedicine approaches developed so far to overcome these CSCs related issues and their future perspectives.
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Stem cells are defined by their capabilities to self-renew and give rise to various types of differentiated cells depending on their potency. They are classified as pluripotent, multipotent, and unipotent as demonstrated through their potential to generate the variety of cell lineages. While pluripotent stem cells may give rise to all types of cells in an organism, Multipotent and Unipotent stem cells remain restricted to the particular tissue or lineages. The potency of these stem cells can be defined by using a number of functional assays along with the evaluation of various molecular markers. These molecular markers include diagnosis of transcriptional, epigenetic, and metabolic states of stem cells. Many reports are defining the particular set of different functional assays, and molecular marker used to demonstrate the developmental states and functional capacities of stem cells. The careful evaluation of all these methods could help in generating standard identifying procedures/markers for them.
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Thrombopoietin receptor (TPOR) is a cytokine receptor protein present on the cell surface. The activation of TPOR by thrombopoietin (TPO) (a glycoprotein hormone) triggers an intracellular cascade of megakaryocytopoiesis for the formation of platelets. Recent studies on ex vivo megakaryocytopoiesis have evolved the possibilities of therapeutics uses. These findings have paved the way for the development of various TPO alternatives (recombinant TPO, peptide, and non-peptide TPO mimetics), which are useful in regenerative medicine. However, these alternatives possess various limitations such as induction of autoimmune effects, high production cost, low specificity, and hence activity. In the present study, a novel peptidic TPO mimetic was designed through computational studies by studying the binding sites of TPO and TMP to TPOR and analogs of known mimetics. Screening of combinatorial library was done through molecular docking using ClusPro. These studies indicated mimetic-9 as a significant molecule since it was found to have better binding score of -938.8 kcal/mol with seven hydrogen bonds and a high number of hydrophobic interactions, than known mimetic TMP with docking score of -798.4 kcal/mol and TMP dimer with docking score of -811.9 kcal/mol for TPOR. Mimetic9-TPOR complex was further assessed by the molecular dynamics simulation, and their complex was found to be stable with an RMSD value of 0.091 Å. While studying the parameters, mimetic-9 was found to have overall good physiochemical properties with positive grand average hydropathy (GRAVY) score and high instability index score and was found to be localized in the extracellular region. The designed mimetic-9 might prove to be a useful lead molecule for mimicking the role of TPO for in vitro platelet production with higher efficiency.
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Ex vivo erythropoiesis methods are being developed for more than a decade now, and all the distinct types of stem cells (such as CD34+ HSCs, ESCs, IPSCs, and extensively proliferating erythropoietic progenitor cells) are defined to bear the potential for large scale RBC production shortly. The various regulating factors at different levels of RBCs production are being explored. Since most of the ex-vivo erythropoiesis protocols mimic the dogma followed by hematopoietic stem cells in vivo to give rise to mature RBCs which essentially deals with the intermediate stages of erythropoiesis such as burst forming unit-erythroid (BFU-E) and committed erythroid colony forming unit-erythroid (CFU-E). In vivo generation of erythroid progenitors (BFU-E/CFU-E) is essentially controlled by several factors including glucocorticoids, inflammation, and stress. Furthermore, regular production of functionally mature /transfusable units of RBCs is possible only through the coordinated regulation of terminal proliferation and differentiation of erythroid progenitors by external signals, such as erythropoietin, SCF, IL-3 and interaction to extracellular matrix protein(s) in a 3D culture system. We discuss these complex intracellular networks of coordinated factors and try to understand their molecular mechanism through gene regulation by transcription factors, and miRNAs that might be helpful in developing the optimal RBCs production protocols for commercial production.