Development of Machine-Learning Algorithms to Predict Attainment of Minimal Clinically Important Difference After Hip Arthroscopy for Femoroacetabular Impingement Yield Fair Performance and Limited Clinical Utility

\ua9 2023 The Author(s). Purpose: To determine whether machine learning (ML) techniques developed using registry data could predict which patients will achieve minimum clinically important difference (MCID) on the International Hip Outcome Tool 12 (iHOT-12) patient-reported outcome measures (PROMs) after arthroscopic management of femoroacetabular impingement syndrome (FAIS). And secondly to determine which preoperative factors contribute to the predictive power of these models. Methods: A retrospective cohort of patients was selected from the UK\u27s Non-Arthroplasty Hip Registry. Inclusion criteria were a diagnosis of FAIS, management via an arthroscopic procedure, and a minimum follow-up of 6 months after index surgery from August 2012 to June 2021. Exclusion criteria were for non-arthroscopic procedures and patients without FAIS. ML models were developed to predict MCID attainment. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC). Results: In total, 1,917 patients were included. The random forest, logistic regression, neural network, support vector machine, and gradient boosting models had AUROC 0.75 (0.68-0.81), 0.69 (0.63-0.76), 0.69 (0.63-0.76), 0.70 (0.64-0.77), and 0.70 (0.64-0.77), respectively. Demographic factors and disease features did not confer a high predictive performance. Baseline PROM scores alone provided comparable predictive performance to the whole dataset models. Both EuroQoL 5-Dimension 5-Level and iHOT-12 baseline scores and iHOT-12 baseline scores alone provided AUROC of 0.74 (0.68-0.80) and 0.72 (0.65-0.78), respectively, with random forest models. Conclusions: ML models were able to predict with fair accuracy attainment of MCID on the iHOT-12 at 6-month postoperative assessment. The most successful models used all patient variables, all baseline PROMs, and baseline iHOT-12 responses. These models are not sufficiently accurate to warrant routine use in the clinic currently. Level of Evidence: Level III, retrospective cohort design; prognostic study

Frequency-interleaved SDM transmission over multicore fiber for next generation short-reach optical interconnect systems

Space division multiplexing (SDM) technique is proposed to overcome the bandwidth density drives of short-reach optical transmission systems by utilizing 8-core multicore fiber (MCF). Intercore crosstalk (XT) and higher order modulation format are the most challenging impairments of SDM based optical interconnect (OI) systems. To satisfy the exponential growth of the Internet traffic a frequency interleaving scheme is applied to short-reach MCF OI transmission systems. The negative effects of spectral overlap and intercore XT is reduced by shifting channel frequencies between adjacent cores. To exploit the full potential of SDM power efficient binary phase shift keying (BPSK) modulation format and digital signal processing such as multiple input multiple output (MIMO) equalization are used

Training and Placement Web Portal

This work present web portal designed for managing t raining and placement data. The objective of this project is to develop a system that can be used by placement cell of a college. The purpose is to design a system that provides functionalities to perform the activities related to placement services. It is based on complete modular architecture. This modularity of the architecture will allow us to replace or add modules in the future as a way to enhance a particular feature of particular situation. This system can be used as an application for the TPO of th e college manages the student information with regards to training and placement. In the present work some of the modules are implemented by means of managing training and placement data. Whereas module responsible for adopting student information, company information and study material require for company placement

Radiolabeled humanized anti-CD3 monoclonal antibody visilizumab for imaging human T-lymphocytes

Visilizumab is an IgG2 humanized monoclonal antibody (mAb) characterized by non-FcγR binding and specific to the CD3 antigen, expressed on more than 95% of circulating resting T-lymphocytes and on activated T-lymphocytes homing in inflamed tissues. We hypothesized that the use of a radiolabeled anti-CD3 antibody might serve as a diagnostic tool for imaging T-cell traffic and lymphocytic infiltration of tissues and organs affected by autoimmune diseases. Here we describe the results of in vitro and animal experiments with 99mTc-succinimidyl-6-hydrazinonicotinate hydrochloride (SHNH)-visilizumab. Methods: For mAb labeling, we used a 2-step method with a heterobifunctional linker SHNH. Several titrations were performed to obtain the best labeling efficiency. In vitro quality controls included stability assay, cysteine challenge, sodium dodecyl sulfate polyacrylamide gel electrophoresis, binding assay, and immunoreactivity assay. In vivo studies by high-resolution images were performed at 6 and 24 h after the injection of 99mTc-SHNH-visilizumab. These included cell-targeting experiments in BALB/c mice xenografted subcutaneously with an increasing number of HuT78 cells in the leg and displaced with an excess of cold antibody. We also studied irradiated severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood mononuclear cells (hPBMCs) and injected with 99mTclabeled visilizumab or control mAb. After dynamic imaging for 3 h, major organs were removed, counted, and processed for immunohistologic examination. Results: Visilizumab was labeled with HYNIC with high labeling efficiency (>90%) and high specific activity (SA; 10,360-11,100 MBq/mg), with retained biochemical integrity and in vitro binding activity to CD3-positive cells. The in vivo targeting experiment showed a proportional increase of specific uptake with the number of injected cells, both at 6 and at 24 h, and the in vivo competition study demonstrated more than 60% decreased uptake after an excess of unlabeled antibody. In SCID mice, hPBMCs in different tissues were detected by 99mTc-labeled visilizumab and confirmed by histology. Conclusion: Visilizumab can be efficiently labeled with 99mTc with high efficiency and SA and could be a valuable tool for the study of human T-lymphocyte trafficking and lymphocytic infiltration of tissues and organs. Copyright © 2009 by the Society of Nuclear Medicine, Inc

Colocalization of different neurotransmitter transporters on synaptic vesicles is sparse except for VGLUT1 and ZnT3

Vesicular transporters (VTs) define the type of neurotransmitter that synaptic vesicles (SVs) store and release. While certain mammalian neurons release multiple transmitters, it is not clear whether the release occurs from the same or distinct vesicle pools at the synapse. Using quantitative single-vesicle imaging, we show that a vast majority of SVs in the rodent brain contain only one type of VT, indicating specificity for a single neurotransmitter. Interestingly, SVs containing dual transporters are highly diverse (27 types) but small in proportion (2% of all SVs), excluding the largest pool that carries VGLUT1 and ZnT3 (34%). Using VGLUT1-ZnT3 SVs, we demonstrate that the transporter colocalization influences the SV content and synaptic quantal size. Thus, the presence of diverse transporters on the same vesicle is bona fide, and depending on the VT types, this may act to regulate neurotransmitter type, content, and release in space and time

Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-α, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with 99mTc or 111In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform ‘evidence-based biological therapy’ of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for therapy decision-making and follow-up

Evaluation and Characterization of Tamarind Gum Polysaccharide: The Biopolymer

Polymers from natural sources are widely used as excipients in the formulation of pharmaceutical dosage forms. The objective of this study was to extract and further characterize the tamarind gum polysaccharide (TGP) obtained from Tamarindus indica as an excipient for biomedical applications. Double distilled water was used as a solvent for the extraction of gum while Ethyl alcohol was used as an antisolvent for the precipitation. The results of the Hausner ratio, Carr’s index and angle of repose were found to be 0.94, 6.25, and 0.14, respectively, which revealed that the powder is free-flowing with good flowability. The gum was investigated for purity by carrying out chemical tests for different phytochemical constituents and only carbohydrates were found to be present. The swelling index was found to be 87 ± 1%, which shows that TGP has good water intake capacity. The pH of the 1% gum solution was found to be neutral, approximately 6.70 ± 0.01. The ash values such as total ash, sulphated ash, acid insoluble ash, and water-soluble ash were found to be 14.00 ± 1.00%, 13.00 ± 0.05%, 14.04 ± 0.57% and 7.29 ± 0.06%, respectively. The IR spectra confirmed the presence of alcohol, amines, ketones, anhydrides groups. The contact angle was <90°, indicating favorable wetting and good spreading of liquid over the surface The scanning electron micrograph (SEM) revealed that the particle is spherical in shape and irregular. DSC analysis shows a sharp exothermic peak at 350 °C that shows its crystalline nature. The results of the evaluated properties showed that TGP has acceptable properties and can be used as a excipient to formulate dosage forms for biomedical applications

Editing of the urease gene by CRISPR-Cas in the diatom Thalassiosira pseudonana

Background: CRISPR-Cas is a recent and powerful addition to the molecular toolbox which allows programmable genome editing. It has been used to modify genes in a wide variety of organisms, but only two alga to date. Here we present a methodology to edit the genome of Thalassiosira pseudonana, a model centric diatom with both ecological significance and high biotechnological potential, using CRISPR-Cas. Results: A single construct was assembled using Golden Gate cloning. Two sgRNAs were used to introduce a precise 37 nt deletion early in the coding region of the urease gene. A high percentage of bi-allelic mutations (≤61.5%) were observed in clones with the CRISPR-Cas construct. Growth of bi-allelic mutants in urea led to a significant reduction in growth rate and cell size compared to growth in nitrate. Conclusions: CRISPR-Cas can precisely and efficiently edit the genome of T. pseudonana. The use of Golden Gate cloning to assemble CRISPR-Cas constructs gives additional flexibility to the CRISPR-Cas method and facilitates modifications to target alternative genes or species