Publications by authors named "Tahir Mahmood"

113 Publications

Advantage of Nanotechnology-Based Genome Editing System and Its Application in Crop Improvement.

Front Plant Sci 2021 28;12:663849. Epub 2021 May 28.

Graduate School of Biotechnology & Crop Biotech Institute, Kyung Hee University, Yongin, South Korea.

Agriculture is an important source of human food. However, current agricultural practices need modernizing and strengthening to fulfill the increasing food requirements of the growing worldwide population. Genome editing (GE) technology has been used to produce plants with improved yields and nutritional value as well as with higher resilience to herbicides, insects, and diseases. Several GE tools have been developed recently, including clustered regularly interspaced short palindromic repeats (CRISPR) with nucleases, a customizable and successful method. The main steps of the GE process involve introducing transgenes or CRISPR into plants via specific gene delivery systems. However, GE tools have certain limitations, including time-consuming and complicated protocols, potential tissue damage, DNA incorporation in the host genome, and low transformation efficiency. To overcome these issues, nanotechnology has emerged as a groundbreaking and modern technique. Nanoparticle-mediated gene delivery is superior to conventional biomolecular approaches because it enhances the transformation efficiency for both temporal (transient) and permanent (stable) genetic modifications in various plant species. However, with the discoveries of various advanced technologies, certain challenges in developing a short-term breeding strategy in plants remain. Thus, in this review, nanobased delivery systems and plant genetic engineering challenges are discussed in detail. Moreover, we have suggested an effective method to hasten crop improvement programs by combining current technologies, such as speed breeding and CRISPR/Cas, with nanotechnology. The overall aim of this review is to provide a detailed overview of nanotechnology-based CRISPR techniques for plant transformation and suggest applications for possible crop enhancement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2021.663849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194497PMC
May 2021

Artificial Intelligence-Based Recognition of Different Types of Shoulder Implants in X-ray Scans Based on Dense Residual Ensemble-Network for Personalized Medicine.

J Pers Med 2021 May 27;11(6). Epub 2021 May 27.

Division of Electronics and Electrical Engineering, Dongguk University, 30 Pildong-ro 1-gil, Jung-gu, Seoul 04620, Korea.

Re-operations and revisions are often performed in patients who have undergone total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RTSA). This necessitates an accurate recognition of the implant model and manufacturer to set the correct apparatus and procedure according to the patient's anatomy as personalized medicine. Owing to unavailability and ambiguity in the medical data of a patient, expert surgeons identify the implants through a visual comparison of X-ray images. False steps cause heedlessness, morbidity, extra monetary weight, and a waste of time. Despite significant advancements in pattern recognition and deep learning in the medical field, extremely limited research has been conducted on classifying shoulder implants. To overcome these problems, we propose a robust deep learning-based framework comprised of an ensemble of convolutional neural networks (CNNs) to classify shoulder implants in X-ray images of different patients. Through our rotational invariant augmentation, the size of the training dataset is increased 36-fold. The modified ResNet and DenseNet are then combined deeply to form a dense residual ensemble-network (DRE-Net). To evaluate DRE-Net, experiments were executed on a 10-fold cross-validation on the openly available shoulder implant X-ray dataset. The experimental results showed that DRE-Net achieved an accuracy, F1-score, precision, and recall of 85.92%, 84.69%, 85.33%, and 84.11%, respectively, which were higher than those of the state-of-the-art methods. Moreover, we confirmed the generalization capability of our network by testing it in an open-world configuration, and the effectiveness of rotational invariant augmentation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jpm11060482DOI Listing
May 2021

Instrument assisted soft tissue mobilization- an emerging trend for soft tissue dysfunction.

J Pak Med Assoc 2021 Mar;71(3):977-981

Department of Physical Therapy Sialkot Medical College, Sialkot Punjab, Pakistan.

Musculoskeletal disorders are common conditions involving joints, muscles, nerves, ligaments and tendons. These disorders affect normal activities and cause discomfort. These discomforts are managed by different types of interventions, including exercise, acupuncture, soft tissue release and manual therapy, as conservative modes of management. Soft tissue release, including active release technique, fascial abrasion, and myo-fascial release are considered effective for musculoskeletal function improvement. Advanced technology-improved and instrument-assisted techniques are being used nowadays. These instruments are sensitive in the localisation, specification and facilitation of the target area with the help of mechanical pressure applied on tissue with movement of specific muscle. Prognosis varies with good outcomes using fewer sessions than the others. But it needs proper localisation of the muscle involved and special training. The advantage considered is that musculoskeletal disorders can also be prevented in practitioners as well.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.47391/JPMA.1168DOI Listing
March 2021

EBCOG position statement on COVID-19 vaccination for pregnant and breastfeeding women.

Eur J Obstet Gynecol Reprod Biol 2021 May 14. Epub 2021 May 14.

EBCOG Standards of Care and Position Statement Group, Victoria Hospital, Kirkcaldy, United Kingdom. Electronic address:

Covid 19 pandemic has led to significant mortality and long term morbidity globally. Pregnant women are at increased risk of severe illness from COVID 19 infection. There is an urgent need for all health authorities and Governments to offer vaccination to all pregnant women especially those with high risk pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2021.05.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120807PMC
May 2021

Light-weighted ensemble network with multilevel activation visualization for robust diagnosis of COVID19 pneumonia from large-scale chest radiographic database.

Appl Soft Comput 2021 Sep 7;108:107490. Epub 2021 May 7.

Division of Electronics and Electrical Engineering, Dongguk University, 30 Pildong-ro 1-gil, Jung-gu, Seoul 04620, Republic of Korea.

Currently, the coronavirus disease 2019 (COVID19) pandemic has killed more than one million people worldwide. In the present outbreak, radiological imaging modalities such as computed tomography (CT) and X-rays are being used to diagnose this disease, particularly in the early stage. However, the assessment of radiographic images includes a subjective evaluation that is time-consuming and requires substantial clinical skills. Nevertheless, the recent evolution in artificial intelligence (AI) has further strengthened the ability of computer-aided diagnosis tools and supported medical professionals in making effective diagnostic decisions. Therefore, in this study, the strength of various AI algorithms was analyzed to diagnose COVID19 infection from large-scale radiographic datasets. Based on this analysis, a light-weighted deep network is proposed, which is the first ensemble design (based on MobileNet, ShuffleNet, and FCNet) in medical domain (particularly for COVID19 diagnosis) that encompasses the reduced number of trainable parameters (a total of 3.16 million parameters) and outperforms the various existing models. Moreover, the addition of a multilevel activation visualization layer in the proposed network further visualizes the lesion patterns as multilevel class activation maps (ML-CAMs) along with the diagnostic result (either COVID19 positive or negative). Such additional output as ML-CAMs provides a visual insight of the computer decision and may assist radiologists in validating it, particularly in uncertain situations Additionally, a novel hierarchical training procedure was adopted to perform the training of the proposed network. It proceeds the network training by the adaptive number of epochs based on the validation dataset rather than using the fixed number of epochs. The quantitative results show the better performance of the proposed training method over the conventional end-to-end training procedure. A large collection of CT-scan and X-ray datasets (based on six publicly available datasets) was used to evaluate the performance of the proposed model and other baseline methods. The experimental results of the proposed network exhibit a promising performance in terms of diagnostic decision. An average F1 score (F1) of 94.60% and 95.94% and area under the curve (AUC) of 97.50% and 97.99% are achieved for the CT-scan and X-ray datasets, respectively. Finally, the detailed comparative analysis reveals that the proposed model outperforms the various state-of-the-art methods in terms of both quantitative and computational performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.asoc.2021.107490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103783PMC
September 2021

Contact lenses coated with hybrid multifunctional ternary nanocoatings (Phytomolecule-coated ZnO nanoparticles:Gallic Acid:Tobramycin) for the treatment of bacterial and fungal keratitis.

Acta Biomater 2021 Apr 15. Epub 2021 Apr 15.

Center of Super-Diamond and Advanced Films (COSDAF) and Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong. Electronic address:

Contact lenses are widely used for visual corrections. However, while wearing contact lenses, eyes typically face discomforts (itching, irritation, burning, etc.) due to foreign object sensation, lack of oxygen permeability, and tear film disruption as opposed to a lack of wetting agents. Eyes are also prone to ocular infections such as bacterial keratitis (BK) and fungal keratitis (FK) and inflammatory events such as contact lens-related acute red eye (CLARE), contact lens peripheral ulcer (CLPU), and infiltrative keratitis (IK) caused by pathogenic bacterial and fungal strains that contaminate contact lenses. Therefore, a good design of contact lenses should adequately address the need for wetting, the supply of antioxidants, and antifouling and antimicrobial efficacy. Here, we developed multifunctional gallic acid (GA), phytomolecules-coated zinc oxide nanoparticles (ZN), and phytomolecules-coated zinc oxide nanoparticles + gallic acid + tobramycin (ZGT)-coated contact lenses using a sonochemical technique. The coated contact lenses exhibited significant antibacterial (>log 5.60), antifungal, and antibiofilm performance against BK-causing multidrug resistant bacteria (Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia. coli) and FK-related pathogenic fungal strains (Candida albicans, Aspergillus fumigatus, and Fusarium solani). The gallic acid, tobramycin, and phytomolecules-coated zinc oxide nanoparticles have different functionalities (-OH, -NH, -COOH, -COH, etc.) that enhanced wettability of the coated contact lenses as compared to that of uncoated ones and further enabled them to exhibit remarkable antifouling property by prohibiting adhesion of platelets and proteins. The coated contact lenses also showed significant antioxidant activity by scavenging DPPH and good cytocompatibility to human corneal epithelial cells and keratinocytes cell lines. STATEMENT OF SIGNIFICANCE: • Multifunctional coated lenses were developed with an efficient sonochemical approach. • Lens surface was modified with nanocoatings of ZnO nanoparticles, gallic acid, and tobramycin. • This synergistic combination endowed the lenses with remarkable antimicrobial activity. • Coated lenses also showed noteworthy antifouling and biofilm inhibition activities. • Coated lenses showed good antioxidant, biocompatibility, and wettability characteristics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2021.04.014DOI Listing
April 2021

Genome-wide association and transcriptome analysis of root color-related genes in Gossypium arboreum L.

Planta 2021 Apr 11;253(5):95. Epub 2021 Apr 11.

School of Agriculture Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, China.

Main Conclusion: The significant number loci and candidate genes of root color in Gossypium arboreum are identified and provide a theoretical basis of root color for cotton. A stimulating phenomenon was observed on the 4th day of sowing in the root color of some G. arboreum accessions that turned red. To disclose the genetic mechanisms of root color formation via genome and transcript levels, we identified the significant number of SNPs and candidate genes that are related to root color through genome-wide association study (GWAS) and RNAseq analysis in G. arboreum. Initially, 215 no. of G. arboreum accessions was collected, and the colors of root on the 4th, 6th and 9th day of germination were recorded. The GWAS demonstrated that 225 significant SNPs and 47 candidate genes have been identified totally. The strongest signal SNP A04_91824 could greatly distinguish the root color with most "C" allele accessions have displayed white and "T" allele accessions displayed red. RNAseq was performed on accessions having the white and red root, and results revealed that 12 and 138 DEGs were detected on 2nd and 4th day, respectively. ACD6, UFGT, and LYM2 were the most related genes of root color, later, verified by qRT-PCR. The mature zone of red and the white roots was observed by the histological section method, and results shown that cells were more closely arranged in the white root, and both average cell length and cell width were longer in the red root. This study will be helpful to cotton breeders for utilization of several elite genes and related SNPs related to root color, in addition to find linkage with economically important traits of interests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00425-021-03622-3DOI Listing
April 2021

Multilevel Deep-Aggregated Boosted Network to Recognize COVID-19 Infection from Large-Scale Heterogeneous Radiographic Data.

IEEE J Biomed Health Inform 2021 06 3;25(6):1881-1891. Epub 2021 Jun 3.

In the present epidemic of the coronavirus disease 2019 (COVID-19), radiological imaging modalities, such as X-ray and computed tomography (CT), have been identified as effective diagnostic tools. However, the subjective assessment of radiographic examination is a time-consuming task and demands expert radiologists. Recent advancements in artificial intelligence have enhanced the diagnostic power of computer-aided diagnosis (CAD) tools and assisted medical specialists in making efficient diagnostic decisions. In this work, we propose an optimal multilevel deep-aggregated boosted network to recognize COVID-19 infection from heterogeneous radiographic data, including X-ray and CT images. Our method leverages multilevel deep-aggregated features and multistage training via a mutually beneficial approach to maximize the overall CAD performance. To improve the interpretation of CAD predictions, these multilevel deep features are visualized as additional outputs that can assist radiologists in validating the CAD results. A total of six publicly available datasets were fused to build a single large-scale heterogeneous radiographic collection that was used to analyze the performance of the proposed technique and other baseline methods. To preserve generality of our method, we selected different patient data for training, validation, and testing, and consequently, the data of same patient were not included in training, validation, and testing subsets. In addition, fivefold cross-validation was performed in all the experiments for a fair evaluation. Our method exhibits promising performance values of 95.38%, 95.57%, 92.53%, 98.14%, 93.16%, and 98.55% in terms of average accuracy, F-measure, specificity, sensitivity, precision, and area under the curve, respectively and outperforms various state-of-the-art methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/JBHI.2021.3072076DOI Listing
June 2021

Effects of age on immune function in broiler chickens.

J Anim Sci Biotechnol 2021 Mar 18;12(1):42. Epub 2021 Mar 18.

The State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.

Background: There are many diseases in poultry, many of which are caused by poor immune function. It is not clear how cytokines and various immune cell functions change with age in modern broilers. The purpose of this study was to explore the patterns of development of the immunity of the broiler chickens in cage.

Results: The results showed that there were 3 development patterns of immunity in the broiler chickens. The first pattern was Down-Up. Cytokines and some immune indicators first decreased and then increased, and the lowest levels of immunity basically occurred from d 6 to 13. The second pattern was Up-Down, and from d 30 to 34, the highest levels of non-specific cellular immunity components, such as the peripheral blood mononuclear macrophage ratio, specific cellular immunity components, such as the peripheral blood helper T (Th) cell ratio and T cell and B cell proliferation activity, and mucosal immunity components, such as the ileal CD4, TGF-β1 and IgA mRNA levels, were observed. The third pattern was Up-Up, and the levels of the non-specific cellular immunity components, such as the serum nitric oxide (NO), C3 and C4 levels, the specific cellular immunity components, such as the spleen index, peripheral blood IL-2, IFN-γ/IL-4, cytotoxic T (Tc) cell ratio, and splenic NF-κB mRNA levels, the humoral immunity components, such as the serum IgG level, the mucosal immunity components, such as the ileal MHC-II, CD3d, TCRβ subunit, TCRζ subunit, IFN-γ, pIgR mRNA and ileal mucosa sIgA levels, were continuing to increase from d 1 to 34.

Conclusions: It could be concluded that the immune system and its function have not developed well in the broiler chickens d 6 to 13 and that the immune system does not mature until d 30 to 34 in the broiler chickens in cages. It is necessary to enhance the immune function of the broiler chickens through nutritional measures from d 1 to 30.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40104-021-00559-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971956PMC
March 2021

EBCOG position statement - Simulation-based training for obstetrics and gynaecology during the COVID-19 pandemic.

Eur J Obstet Gynecol Reprod Biol 2021 Mar 9;258:457-458. Epub 2020 Dec 9.

Victoria Hospital, Kirkcaldy, Scotland, United Kingdom; EBCOG Standards of Care and Position Statements Group, United Kingdom. Electronic address:

The specialty of Obstetrics and Gynaecology has been on the forefront of introducing simulation in post graduate education for the past two decades. Simulation training is known to enhance psychomotor skills and is considered an important step in the transition from classroom learning to clinical practice. Training on simulators allows trainees to acquire basic skills before getting involved in day to day care in real life situations. Clinical circumstances around the COVID 19 pandemic have highlighted the key importance of simulation training in delivering post graduate curriculum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2020.12.002DOI Listing
March 2021

T-spherical fuzzy power aggregation operators and their applications in multi-attribute decision making.

J Ambient Intell Humaniz Comput 2021 Jan 22:1-14. Epub 2021 Jan 22.

Department of Mathematics and Statistics, International Islamic University Islamabad, Islamabad, Pakistan.

The paper aims to present the concept of power aggregation operators for the T-spherical fuzzy sets (T-SFSs). T-SFS is a powerful concept, with four membership functions denoting membership, abstinence, non-membership and refusal degree, to deal with the uncertain information as compared to other existing fuzzy sets. On the other hand, the relationship between the different pairs of the attributes are well recorded in terms of power operators. Thus, keeping these advantages of T-SFSs and power operator, the objective of this work is to define several weighted averaging and geometric power aggregation operators. The stated operators named as T-spherical fuzzy weighted, ordered weighted, hybrid averaging and geometric operators for the collection of the T-SFSs. The various properties and the special cases of them are also derived. Further, the consequences of proposed new power aggregation operators are studied in view of some constraints. Finally, a multiple attribute decision making algorithm, based on the proposed operators, is established to solve the problems with uncertain information and illustrate with numerical examples. A comparative study, superiority analysis and discussion of the proposed approach are furnished to confirm the approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12652-020-02600-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819830PMC
January 2021

Psychosocial Barriers of Public Transport Use and Social Exclusion among Older Adults: Empirical Evidence from Lahore, Pakistan.

Int J Environ Res Public Health 2020 12 29;18(1). Epub 2020 Dec 29.

Department of Technology, School of Science and Technology, The Open University of Hong Kong, SAR, China.

Transport planning and public health have been intertwined historically. The health impact of public transport services, such as social exclusion, is a widely discussed research topic. Social exclusion is a paramount concern for older adults' health in the wake of emerging global challenges. However, there remains a significant research gap on how psychosocial barriers faced by older adults in using public transport services influence the social exclusion behavior. The present research provides empirical evidence and shows the impact of certain psychosocial barriers of public transportation on older adults' social exclusion. A total of 243 Pakistani older adults (aged 60-89 years old) voluntarily participated in this cross-sectional study. The participants provided self-reports on their psychosocial barriers (including perceived norms, attitude, personal ability, habits, neighborhood social constraints, and intention) and the corresponding social exclusion. Partial Least Square Structural Equation Modeling (PLS-SEM) was utilized for the data analysis. The structural path model supported the significant associations between psychosocial barriers and social exclusion. Except for perceived descriptive norms, all other psychosocial barriers predicted older adults' social exclusion. The research portrays the significance of the psychosocial factors to examine social exclusion and offers practical implications for urban and transport planners. The concerned policymakers can use the research findings to develop age-sensitive, socially sustainable, and healthy cities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18010185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794845PMC
December 2020

Comprehensive Computer-Aided Decision Support Framework to Diagnose Tuberculosis From Chest X-Ray Images: Data Mining Study.

JMIR Med Inform 2020 Dec 7;8(12):e21790. Epub 2020 Dec 7.

Division of Electronics and Electrical Engineering, Dongguk University, Seoul, Republic of Korea.

Background: Tuberculosis (TB) is one of the most infectious diseases that can be fatal. Its early diagnosis and treatment can significantly reduce the mortality rate. In the literature, several computer-aided diagnosis (CAD) tools have been proposed for the efficient diagnosis of TB from chest radiograph (CXR) images. However, the majority of previous studies adopted conventional handcrafted feature-based algorithms. In addition, some recent CAD tools utilized the strength of deep learning methods to further enhance diagnostic performance. Nevertheless, all these existing methods can only classify a given CXR image into binary class (either TB positive or TB negative) without providing further descriptive information.

Objective: The main objective of this study is to propose a comprehensive CAD framework for the effective diagnosis of TB by providing visual as well as descriptive information from the previous patients' database.

Methods: To accomplish our objective, first we propose a fusion-based deep classification network for the CAD decision that exhibits promising performance over the various state-of-the-art methods. Furthermore, a multilevel similarity measure algorithm is devised based on multiscale information fusion to retrieve the best-matched cases from the previous database.

Results: The performance of the framework was evaluated based on 2 well-known CXR data sets made available by the US National Library of Medicine and the National Institutes of Health. Our classification model exhibited the best diagnostic performance (0.929, 0.937, 0.921, 0.928, and 0.965 for F1 score, average precision, average recall, accuracy, and area under the curve, respectively) and outperforms the performance of various state-of-the-art methods.

Conclusions: This paper presents a comprehensive CAD framework to diagnose TB from CXR images by retrieving the relevant cases and their clinical observations from the previous patients' database. These retrieval results assist the radiologist in making an effective diagnostic decision related to the current medical condition of a patient. Moreover, the retrieval results can facilitate the radiologists in subjectively validating the CAD decision.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/21790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752539PMC
December 2020

The pandemic paradox: domestic violence and happiness of women.

PeerJ 2020 24;8:e10472. Epub 2020 Nov 24.

Department of Technology, School of Science and Technology, The Open University of Hong Kong, Kowloon, Hong Kong.

Background: Across the globe, lockdowns have been enforced as a pandemic response to COVID-19. Such lockdown coupled with school closures and stay-at-home orders made women more vulnerable in terms of higher responsibility and spending more time with an abusive partner, if any.

Methods: This study investigates the situation of women during COVID-19 induced lockdown by focusing on their happiness and inquiring about the incidence of violence. Using the zero-inflated negative binomial model, our findings ascertained that family settings, type of relationship with a spouse, and age significantly affects the positive count of violence during the lockdown. We further estimated the determinants of happiness and found that years of schooling, the role of women in household decision making, and feeling empowered is affecting their happiness.

Results: Women having higher education have more odds of zero violence. Unemployed women and women who are not working have higher odds of zero violence as compared to women who are working. During this lockdown after the COVID-19 pandemic, women living in urban areas, having higher education, having an adequate household income to meet the expenditures, having lesser anxiety, not facing violence, feeling empowered when their husband is around, and have higher decision-making power are happier.

Discussion And Conclusion: The study is important in the context of happiness and violence inflicted on women during the lockdown and provides the basis to improve the pandemic response policy. The inclusion of women's safety and happiness in pandemic response policy is important to ensure the well-being of women and to devise better health and economic policy. Our estimates suggest higher education results in less incidence of violence which could be argued as desirable outcomes for building healthy, productive, and happy communities. In addition to this, as pandemic induced lock-down is likely to result in higher unemployment across the globe including Pakistan, therefore, in light of our estimates pertaining to the role of unemployment in the incidence of violence, policymakers should deploy more resources to enhance income and to combat the rising unemployment. As a counter-intuitive outcome of these policy interventions, incidence of violence will be dampened, educational attainment and women empowerment will be increased which will certainly increase happiness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.10472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694561PMC
November 2020

Automated Diagnosis of Various Gastrointestinal Lesions Using a Deep Learning-Based Classification and Retrieval Framework With a Large Endoscopic Database: Model Development and Validation.

J Med Internet Res 2020 11 26;22(11):e18563. Epub 2020 Nov 26.

Division of Electronics and Electrical Engineering, Dongguk University, Seoul, Republic of Korea.

Background: The early diagnosis of various gastrointestinal diseases can lead to effective treatment and reduce the risk of many life-threatening conditions. Unfortunately, various small gastrointestinal lesions are undetectable during early-stage examination by medical experts. In previous studies, various deep learning-based computer-aided diagnosis tools have been used to make a significant contribution to the effective diagnosis and treatment of gastrointestinal diseases. However, most of these methods were designed to detect a limited number of gastrointestinal diseases, such as polyps, tumors, or cancers, in a specific part of the human gastrointestinal tract.

Objective: This study aimed to develop a comprehensive computer-aided diagnosis tool to assist medical experts in diagnosing various types of gastrointestinal diseases.

Methods: Our proposed framework comprises a deep learning-based classification network followed by a retrieval method. In the first step, the classification network predicts the disease type for the current medical condition. Then, the retrieval part of the framework shows the relevant cases (endoscopic images) from the previous database. These past cases help the medical expert validate the current computer prediction subjectively, which ultimately results in better diagnosis and treatment.

Results: All the experiments were performed using 2 endoscopic data sets with a total of 52,471 frames and 37 different classes. The optimal performances obtained by our proposed method in accuracy, F1 score, mean average precision, and mean average recall were 96.19%, 96.99%, 98.18%, and 95.86%, respectively. The overall performance of our proposed diagnostic framework substantially outperformed state-of-the-art methods.

Conclusions: This study provides a comprehensive computer-aided diagnosis framework for identifying various types of gastrointestinal diseases. The results show the superiority of our proposed method over various other recent methods and illustrate its potential for clinical diagnosis and treatment. Our proposed network can be applicable to other classification domains in medical imaging, such as computed tomography scans, magnetic resonance imaging, and ultrasound sequences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/18563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728528PMC
November 2020

A Novel Fusion of IL-10 Engineered to Traffic across Intestinal Epithelium to Treat Colitis.

J Immunol 2020 12 4;205(11):3191-3204. Epub 2020 Nov 4.

Applied Molecular Transport, South San Francisco, CA 94080; and

IL-10 is a potent anti-inflammatory cytokine capable of suppressing a number of proinflammatory signals associated with intestinal inflammatory diseases, such as ulcerative colitis and Crohn's disease. Clinical use of human IL-10 (hIL-10) has been limited by anemia and thrombocytopenia following systemic injection, side effects that might be eliminated by a gut-restricted distribution. We have identified a transcytosis pathway used by cholix, an exotoxin secreted by nonpandemic forms of the intestinal pathogen A nontoxic fragment of the first 386 aa of cholix was genetically fused to hIL-10 to produce recombinant AMT-101. In vitro and in vivo characterization of AMT-101 showed it to efficiently cross healthy human intestinal epithelium (SMI-100) by a vesicular transcytosis process, activate hIL-10 receptors in an engineered U2OS osteosarcoma cell line, and increase cellular phospho-STAT3 levels in J774.2 mouse macrophage cells. AMT-101 was taken up by inflamed intestinal mucosa and activated pSTAT3 in the lamina propria with limited systemic distribution. AMT-101 administered to healthy mice by oral gavage or to cynomolgus monkeys (nonhuman primates) by colonic spray increased circulating levels of IL-1R antagonist (IL-1Ra). Oral gavage of AMT-101 in two mouse models of induced colitis prevented associated pathological events and plasma cytokine changes. Overall, these studies suggest that AMT-101 can efficiently overcome the epithelial barrier to focus biologically active IL-10 to the intestinal lamina propria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.2000848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682254PMC
December 2020

Coronary artery calcium testing in low-intermediate risk symptomatic patients with suspected coronary artery disease: An effective gatekeeper to further testing?

PLoS One 2020 13;15(10):e0240539. Epub 2020 Oct 13.

Center for Prevention of Cardiovascular Disease, Section on Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United States of America.

Computed tomography for quantification of coronary artery calcium (CAC) is a simple non-invasive tool to assess atherosclerotic plaque burden. CAC is highly correlated with coronary atherosclerosis and is a robust predictor of cardiovascular outcomes. Recently, the 2018 ACC/AHA Cholesterol Guidelines endorsed the use of CAC scores in asymptomatic, intermediate risk individuals where the decision to initiate stain therapy is uncertain. However, whether quantification of CAC may play a role in the assessment of symptomatic individuals remains a matter of debate. In this review, we examine the evidence for the use of CAC in low-intermediate risk patients with chest pain. This appraisal places a particular focus on the growing body of literature supporting the negative predictive value of a CAC score of zero to rule out significant coronary artery disease in those without high-risk features. We also evaluate current guidelines, limitations, and future research directions for CAC scoring in this important subgroup of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240539PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553353PMC
December 2020

Incredible Role of Osmotic Adjustment in Grain Yield Sustainability under Water Scarcity Conditions in Wheat ( L.).

Plants (Basel) 2020 Sep 15;9(9). Epub 2020 Sep 15.

Institute of Biological Sciences, University of Talca, Talca 3460000, Chile.

Interrogations of local germplasm and landraces can offer a foundation and genetic basis for drought tolerance in wheat. Potential of drought tolerance in a panel of 30 wheat genotypes including varieties, local landraces, and wild crosses were explored under drought stress (DS) and well-watered (WW) conditions. Considerable variation for an osmotic adjustment (OA) and yield components, coupled with genotype and environment interaction was observed, which indicates the differential potential of wheat genotypes under both conditions. Reduction in yield per plant (YP), thousand kernel weight (TKW), and induction of OA was detected. Correlation analysis revealed a strong positive association of YP with directly contributing yield components under both environments, indicating the impotence of these traits as a selection-criteria for the screening of drought-tolerant genotypes for drylands worldwide. Subsequently, the association of OA with TKW which contributes directly to YP, indicates that wheat attains OA to extract more water from the soil under low water-potential. Genotypes including WC-4, WC-8 and LLR-29 showed more TKW under both conditions, among them; LLR-29 also has maximum OA and batter yield comparatively. Result provides insight into the role of OA in plant yield sustainability under DS. In this study, we figure out the concept of OA and its incredible role in sustainable plant yield in wheat.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/plants9091208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569908PMC
September 2020

Current perspective on diagnosis, epidemiological assessment, prevention strategies, and potential therapeutic interventions for severe acute respiratory infections caused by 2019 novel coronavirus (SARS-CoV-2).

Hum Vaccin Immunother 2020 12 3;16(12):3001-3010. Epub 2020 Sep 3.

Department of Systems Engineering and Engineering Management, City University of Hong Kong , Kowloon, Hong Kong.

Coronaviruses are single-stranded RNA viruses that cause severe respiratory, enteric, and systemic infections in a vast range of hosts, including man, fish, mammals, and avian. Scientific interest has heightened on coronaviruses after the emergence of the 2019 novel Coronavirus (SARS-CoV-2). This review provides current perspectives on morphology, genetic diversity, transmission characteristics, replication cycle, diagnostic approaches, epidemiological assessment, and prevention strategies against the SARS-CoV-2. Moreover, different potential biotherapeutics such as small drug molecules, different vaccines, and immunotherapies to control severe acute respiratory infections caused by 2019 novel coronavirus (SARS-CoV-2) are repurposed and discussed with different mechanistic approaches. The current growth trends of the SARS-CoV-2/COVID-19 outbreak globally and preventive measures are briefly discussed. Furthermore, the lessons learned from the COVID-19 outbreak, so far, concluding remarks and future directions for controlling for COVID-19, are also recommended for a safer tomorrow.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21645515.2020.1794684DOI Listing
December 2020

EBCOG position statement on "Ethical analysis of cross-border reproductive care".

Eur J Obstet Gynecol Reprod Biol 2020 Sep 15;252:568-569. Epub 2020 Jul 15.

Chair Standards of Care and Position Statements Working Group, European Board and College of Obstetrics and Gynaecology (EBCOG), UK.

Cross border movement of couples to seek assisted conception treatments which are not available in their own countries are creating lots of ethical issues. Eu countires should work together to deliver couple centered care within a legal framework.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2020.07.027DOI Listing
September 2020

Reply to the IUGA obstetric pelvic floor trauma special interest group's response to Gachon B et al/EBCOG re: Should we advise women that pre-labor caesarean section prevents pelvic floor dysfunction?

Eur J Obstet Gynecol Reprod Biol 2020 10 13;253:336-337. Epub 2020 Jul 13.

Department of Obstetrics and Gynaecology, La Milétrie University Hospital, Poitiers, France; INSERM CIC-P 1402, La Milétrie University Hospital, Poitiers, France; INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Gender, Sexuality and Health Team, Univ Paris-Sud, UMRS 1018, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2020.07.023DOI Listing
October 2020

Dietary supplementation with vitamin C ameliorates the adverse effects of Salmonella Enteritidis-challenge in broilers by shaping intestinal microbiota.

Poult Sci 2020 Jul 24;99(7):3663-3674. Epub 2020 Apr 24.

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, People's Republic of China. Electronic address:

Salmonella Enteritidis (SE) infection is not only a leading cause of poor production performance and compromised animal welfare in broilers but also a potential threat to public health. Two experiments were conducted to evaluate the effects of dietary supplemental vitamin C (VC) on SE challenged-broilers. In experiment 1, one hundred eighty 1-day-old Arbor Acre broilers were randomly allocated into 3 treatments, with 0, 500, or 1,000 mg/kg VC included in the diet. In experiment 2, dietary VC at 0 or 500 mg/kg, with or without SE challenge was applied in a 2 × 2 factorial arrangement in 6 randomized complete blocks. In experiment 1, addition with 500 mg/kg VC increased BW and infectious bursal disease (IBD) titer of broilers on 35 D (P < 0.05), whereas 1,000 mg/kg VC had no effects on the IBD titer (P > 0.05) compared with the control group. In experiment 2, SE challenge depressed BW on 11 and 21 D (P < 0.05 and P = 0.088, respectively), whereas increased mortality and hepatic bacterial translocation (P < 0.05) on 21 D. Further, SE challenge resulted in lower villus height in jejunum, lower microbial richness, and diversity, whereas higher abundance of Enterobacteriaceae in cecum (P < 0.05). Importantly, supplementation with VC increased BW on both 21 and 35 D (P < 0.05 and P = 0.088, respectively) and enhanced the intestinal health by improving villus morphology and microbial structure as indicated by higher cecal microbial richness and Firmicutes to Bacteroidetes ratio, while lower abundance of Enterobacteriaceae (P < 0.05). In addition, birds fed with 500 mg/kg VC in the diet had significantly increased jejunal secretory immunoglobulin A levels, T lymphocytes stimulation index, and serum total antioxidant capability compared with groups without VC (P < 0.05). In conclusion, SE challenge induced lower production performance and higher mortality in broilers. However, dietary supplementation with VC ameliorated SE-caused damage in broilers by improving the intestinal health, partly mediated by shaping the structure of cecal microbiota.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psj.2020.03.062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597860PMC
July 2020

Effects of dietary vitamins supplementation level on the production performance and intestinal microbiota of aged laying hens.

Poult Sci 2020 Jul 26;99(7):3594-3605. Epub 2020 Apr 26.

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, People's Republic of China. Electronic address:

The objective of this study was to investigate the effects of higher vitamins supplementation level on the performance, immunity, and intestinal microbiota of old laying hens. Twelve birds were randomly chosen from 312 healthy, 65-wk-old Hy-Line Brown layers for sampling after a 7-wk acclimation period. The remaining 300 hens were randomly allocated to 1 of 4 dietary treatments for a 13-wk feeding trial: basal diet (CON), basal diet with 2-fold supplementation level of lipid-soluble vitamins (LV), 2-fold supplementation level of water-soluble vitamins (WV), or 2-fold supplementation level of both lipid-soluble and water-soluble vitamins (BV), respectively. Compared with 72-wk-old laying hens, the 85-wk-old laying hens showed declined egg quality, which implied by inferior eggshell strength and yolk color (P < 0.05). However, after 13 wks feeding trial, the birds in WV group had higher yellowness of yolk color, and LV group had increased laying rate (P < 0.05) compared with CON. Meanwhile, WV and/or BV groups showed improved GSH/GSSG levels in liver and increased secretory immunoglobulin A concentrations in jejunum compared with CON (P < 0.05). In addition, higher dietary vitamin supplementation levels significantly altered the composition of intestinal microbiota, as evidenced by increased abundance of ileal Lactobacillus, whereas reduced richness of ileal Romboutsia, Turicibacter, and cecal Faecalibacterium (P < 0.05) in WV group and increased cecal Megasphaera and Phascolarctobacterium (P < 0.05) in LV group compared with CON group. In conclusion, higher vitamin supplementation levels in the diet could improve laying performance and egg quality of aged hens, which was closely correlated with the increased abundance of beneficial microbiota in the intestine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psj.2020.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597815PMC
July 2020

Deep Learning-Based Detection of Pigment Signs for Analysis and Diagnosis of Retinitis Pigmentosa.

Sensors (Basel) 2020 Jun 18;20(12). Epub 2020 Jun 18.

Division of Electronics and Electrical Engineering, Dongguk University, 30 Pildong-ro 1-gil, Jung-gu, Seoul 04620, Korea.

Ophthalmological analysis plays a vital role in the diagnosis of various eye diseases, such as glaucoma, retinitis pigmentosa (RP), and diabetic and hypertensive retinopathy. RP is a genetic retinal disorder that leads to progressive vision degeneration and initially causes night blindness. Currently, the most commonly applied method for diagnosing retinal diseases is optical coherence tomography (OCT)-based disease analysis. In contrast, fundus imaging-based disease diagnosis is considered a low-cost diagnostic solution for retinal diseases. This study focuses on the detection of RP from the fundus image, which is a crucial task because of the low quality of fundus images and non-cooperative image acquisition conditions. Automatic detection of pigment signs in fundus images can help ophthalmologists and medical practitioners in diagnosing and analyzing RP disorders. To accurately segment pigment signs for diagnostic purposes, we present an automatic RP segmentation network (RPS-Net), which is a specifically designed deep learning-based semantic segmentation network to accurately detect and segment the pigment signs with fewer trainable parameters. Compared with the conventional deep learning methods, the proposed method applies a feature enhancement policy through multiple dense connections between the convolutional layers, which enables the network to discriminate between normal and diseased eyes, and accurately segment the diseased area from the background. Because pigment spots can be very small and consist of very few pixels, the RPS-Net provides fine segmentation, even in the case of degraded images, by importing high-frequency information from the preceding layers through concatenation inside and outside the encoder-decoder. To evaluate the proposed RPS-Net, experiments were performed based on 4-fold cross-validation using the publicly available Retinal Images for Pigment Signs (RIPS) dataset for detection and segmentation of retinal pigments. Experimental results show that RPS-Net achieved superior segmentation performance for RP diagnosis, compared with the state-of-the-art methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s20123454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349531PMC
June 2020

Why under five children are stunted in Pakistan? A multilevel analysis of Punjab Multiple indicator Cluster Survey (MICS-2014).

BMC Public Health 2020 Jun 17;20(1):952. Epub 2020 Jun 17.

College of Public Health Sciences, Chulalongkorn University, Bangkok, Thailand.

Background: Pakistan is facing a serious problem of child under-nutrition as about 38% of children in Pakistan are stunted. Punjab, the largest province by population and contributes high gross domestic product (GDP) share in economy has reported 27% moderately and 10% severely stunted children of less than 5 years. Thus, this study aims at examining the determinants of stunting (moderate and severe) at different level of hierarchy empirically in Punjab province of Pakistan.

Methodology: Data for this study is coming from Punjab Multiple Indicators Cluster Survey (MICS-2014), used two-stage, stratified cluster sampling approach. Sub-national level data covering urban and rural areas were used for this study consists of 25,067 children less than 5 year's ages, from nine administrative divisions and 36 districts of Punjab province of Pakistan. Descriptive statistics and multilevel hierarchical models were estimated. Multilevel data analyses have an advantage because it provides robust standard error estimates and helps in finding variation in the data at various levels.

Results: Punjab has a stunting prevalence of about 27% moderately and 10% severely stunted children of less than 5 years. The results depict that increasing the age of the child, increasing birth order, illiterate mothers and fathers, lack of sanitation facilities and being poor are associated significantly with the likelihood of moderate and severe stunting. Surprisingly, there is a gender bias in stunting in Punjab, Pakistan and being a girl child is more likely associated with moderate and severe stunting, which shows the patriarchal nature of the society and a substantial prevalence of gender bias in household resource allocations.

Conclusion: This outcome of our analysis points towards targeting not only households (focus on girls) but also their families and communities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12889-020-09110-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302159PMC
June 2020

Transcriptome analysis reveals a molecular understanding of nicotinamide and butyrate sodium on meat quality of broilers under high stocking density.

BMC Genomics 2020 Jun 18;21(1):412. Epub 2020 Jun 18.

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.

Background: In recent years, increased attention has been focused on breast muscle yield and meat quality in poultry production. Supplementation with nicotinamide and butyrate sodium can improve the meat quality of broilers. However, the potential molecular mechanism is not clear yet. This study was designed to investigate the effects of supplementation with a combination of nicotinamide and butyrate sodium on breast muscle transcriptome of broilers under high stocking density. A total of 300 21-d-old Cobb broilers were randomly allocated into 3 groups based on stocking density: low stocking density control group (L; 14 birds/m), high stocking density control group (H; 18 birds/m), and high stocking density group provided with a combination of 50 mg/kg nicotinamide and 500 mg/kg butyrate sodium (COMB; 18 birds/m), raised to 42 days of age.

Results: The H group significantly increased cooking losses, pH decline and activity of lactate dehydrogenase in breast muscle when compared with the L group. COMB showed a significant decrease in these indices by comparison with the H group (P < 0.05). The transcriptome results showed that key genes involved in glycolysis, proteolysis and immune stress were up-regulated whereas those relating to muscle development, cell adhesion, cell matrix and collagen were down-regulated in the H group as compared to the L group. In contrast, genes related to muscle development, hyaluronic acid, mitochondrial function, and redox pathways were up-regulated while those associated with inflammatory response, acid metabolism, lipid metabolism, and glycolysis pathway were down-regulated in the COMB group when compared with the H group.

Conclusions: The combination of nicotinamide and butyrate sodium may improve muscle quality by enhancing mitochondrial function and antioxidant capacity, inhibiting inflammatory response and glycolysis, and promoting muscle development and hyaluronic acid synthesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-020-06827-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302154PMC
June 2020

Effect of 2-hydroxy-4-(methylthio) butanoic acid and acidifier on the performance, chyme pH, and microbiota of broilers.

Anim Sci J 2020 Jan-Dec;91(1):e13409

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China.

This study was aimed to explore the comparative acidifying properties of 2-hydroxy-4-(methylthio) butanoic acid (HMTBA) and a combination of DL-methionine (DLM) and acidifier in male broiler production. A total of 480 1-day-old broiler chicks were randomly divided into four treatments: A (low HMTBA, 0.057% HMTBA); B (low acidifier, 0.05% DLM + 0.057% acidifier); C (high HMTBA, 0.284% HMTBA); and D (high acidifier, 0.25% DLM + 0.284% acidifier). At 21 d, growth performance, chyme pH, digestive enzyme activities, and intestinal microflora were measured. The pH of crop, gizzard, and ileum contents was higher in the HMTBA treatment group than in DLM + acidifier treatment group. Furthermore, acidifier supplementation promoted growth of butyrate-producing bacteria such as Faecalibacterium, whereas high HMTBA (0.284%) inhibited the proliferation of acid-producing bacteria including Roseburia and Collinsella. The chymotrypsin activity was lower in the HMTBA group than in the DLM + acidifier group. In contrast, high-level HMTBA group showed higher average daily gain and average daily feed intake than the DLM + acidifier group. These results suggested that HMTBA work through different pathways with DLM plus acidifier.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/asj.13409DOI Listing
October 2020

How to reduce the potential risk of vertical transmission of SARS-CoV-2 during vaginal delivery?

Eur J Obstet Gynecol Reprod Biol 2020 Jul 6;250:246-249. Epub 2020 May 6.

Standards of Care and Position Statements Group of EBCOG (Brussels) and Department of Obstetrics and Gynaecology, Victoria Hospital, Kirkcaldy, Scotland, United Kingdom.

The risk of vertical transmission during vaginal delivery in COVID-19 pregnant patients is currently a topic of debate. Obstetric norms on vaginal birth assistance to reduce the potential risk of perinatal infection should be promoted by ensuring that the risk of contamination from maternal anus and faecal material is reduced during vaginal delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2020.04.065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200385PMC
July 2020

Breech presentation at term: Is it the time to revisit the mode: An introduction to the Mini-Symposium commissioned by the European Board and College of Obstetrics and Gynaecology (EBCOG).

Authors:
Tahir Mahmood

Eur J Obstet Gynecol Reprod Biol 2020 Sep 9;252:570-571. Epub 2020 Apr 9.

Department of Obstetrics and Gynaecology, Victoria Hospital, Kirkcaldy, Scotland, United Kingdom; Chair Standards of Care and Position Statements Working Group of the EBCOG, Brussels, Belgium. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2020.03.049DOI Listing
September 2020

Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies.

Eur J Prev Cardiol 2020 Apr 10:2047487320915803. Epub 2020 Apr 10.

Center for Preventive Cardiology, Wake Forest University Baptist Medical Center, Section on Cardiovascular Medicine, USA.

Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors consistently reduce low-density lipoprotein cholesterol (LDL-C) by 50-60% and lipoprotein(a) (Lp(a)) by 20-30%, but the mechanism of Lp(a) lowering remains unclear. If Lp(a) is cleared by the LDL receptor, similar to LDL-C, then one would expect PCSK9 inhibition to induce a concordant LDL-C/Lp(a) response in an approximately 2:1 ratio. We aim to determine the prevalence of discordant plasma LDL-C/Lp(a) response to the PCSK9 inhibitor alirocumab.

Methods: This is a post hoc, pooled analysis of 10 randomized controlled trials from the ODYSSEY Phase 3 clinical trial program for alirocumab. Patients enrolled in the trials were high cardiovascular risk and/or with heterozygous familial hypercholesterolemia. The primary end point was prevalence of discordant LDL-C/Lp(a) response to alirocumab at 24 weeks. Discordant response was defined as LDL-C reduction >35% and Lp(a) reduction ≤10%, or LDL-C reduction ≤35% and Lp(a) reduction >10%.

Results: Of the 1709 patients in the pooled study cohort, 62.4% were male, and the mean age was 59.2 (SD: 11.0) years. Baseline mean LDL-C was 126.5 (SD: 46.3) mg/dL and baseline median Lp(a) was 46.9 (interquartile range: 21.8-89.0) mg/dL. Total prevalence of discordant LDL-C/Lp(a) response was 21.5% (12.6% with LDL-C >35% reduction and Lp(a) ≤10% reduction; 8.9% with LDL-C ≤35% reduction and Lp(a) >10% reduction). Baseline Lp(a) and familial hypercholesterolemia status did not affect discordance.

Conclusion: A high prevalence of discordant LDL-C/Lp(a) response was observed with alirocumab, further suggesting that PCSK9 inhibitor therapy with alirocumab reduces plasma Lp(a) through alternative pathways to LDL receptor clearance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2047487320915803DOI Listing
April 2020