A Life-Long Learning XAI Metaheuristic-based Type-2 Fuzzy System for Solar Radiation Modelling

Solar photovoltaic (PV) power generation is one of the most important sources for renewable energy. However, PV power generation is entirely dependent on the amount of downward solar radiation reaching the solar cells. This is determined by uncertain and uncontrollable meteorological factors such as temperature, humidity, wind speed, and direction, as well as other factors such as topographical characteristics. Good solar radiation prediction models can increase energy output while decreasing the operation costs of photovoltaic power generation. For example, in some provinces in China, PV stations are required to upload short-term online power forecast information to power dispatching agencies. Numerous AI, statistical, and numerical weather prediction models have been used in many real-world renewable energy applications, with a focus on modeling accuracy. However, there is a need for Explainable AI (XAI) models that could be easily understood, analyzed, and augmented by the stakeholders. In this paper, we present a compact, explainable, and lifelong learning metaheuristic-based Interval Type-2 Fuzzy Logic System (IT2FLS) for Solar Radiation Modeling. The generated model will be composed of a small number of short IF-Then rules that have been optimized via simulated annealing to produce models with high prediction accuracy. These models are updated through a life-long learning approach to maximize their accuracy and maintain interpretability. In the process of lifelong learning, the proposed method transferred the model's knowledge to new geographical locations with minimal forgetting. The proposed method achieved good prediction accuracy and outperformed on new geographical locations other transparent and black-box models by 13.2% as well as maintaining excellent generalization ability. The resulting models have been evaluated and accepted by experts, and thanks to the generated transparency, the experts were able to augment the models with their expertise, which increased the models' accuracy

Blue biotechnology: Computational screening of sarcophyton cembranoid diterpenes for SARS-CoV-2 main protease inhibition

The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (Mpro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target Mpro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 Mpro inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as Mpro inhibitors with ΔGbinding \u3c -33.0 kcal/mol. Binding energy and structural analyses of the most potent Sarcophyton inhibitor, bislatumlide A (340), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that 340 has a higher binding affinity against Mpro than darunavir with ΔGbinding values of -43.8 and -34.8 kcal/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for 340; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that 340 has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of 340 as an antiviral agent against SARS-CoV-2

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

AbstractDevelopmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.</jats:p

Coronary Artery Bypass Grafting (CABG) versus Percutaneous Coronary Intervention (PCI) in treatment of left main coronary artery disease

BackgroundCoronary artery bypass graft surgery (CABG) has been widely used for left main coronary artery disease (LMCAD). Percutaneous coronary intervention (PCI) has become an option for this condition.AimsTo summarize the current evidence that compare between CABG vs. PCI in regards to ‎cardiac death, stroke, and myocardial infarction.‎Methods We searched randomized trials of treatment of LMCAD with PubMed, Google Scholar, and EBSCO.Results Five randomized studies were retrieved, which compared the efficacy between CABG vs. PCI in treatment of LMCAD.ConclusionPCI may be reasonable management of patients with LM stenosis involving distal bifurcation or with coexisting multivessel disease

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Is the Intramedullary Skeletal Kinetic Distractor a Safe Measure for Bone Lengthening? A Systematic Review

Background: The intramedullary skeletal kinetic distractor (ISKD) is one of the relatively recent methods developed to overcome the complications of conventional bone lengthening methods, such as external fixators. These complications include pain, muscle transfixation, pin-tract infection, reduced joint motion, and prolonged fixation time. However, ISKD-specific complications such as uncontrollable lengthening and hardware failure make the outcomes of ISKD lengthening questionable. In this article, we review published literature on the efficacy and complications of the ISKD device. Methods: A database search was conducted in PubMed, Ovid Medline, Ovid Full Text, Springer link, EBSCO Medline, Science Direct, ISI Web of Knowledge, and Google Scholar. We included English articles with extractable data about the study population and outcomes, reporting ISKD implantation in the femur or tibia of skeletally mature patients. The included studies were too heterogeneous for a meta-analysis to be performed. Results: Fifteen of 89 potentially relevant citations were found to match the inclusion criteria. The most common causes of limb-length discrepancy indicating an ISKD implantation were traumatic and congenital. The average lengthening achieved, average patient discharge period, mean follow-up time, average consolidation time and index, average distraction time and index, and number of patients requiring additional operations as well as other outcome measures are discussed in this article. The most common complications were runaway nail, difficulty in achieving lengthening, and poor bone regenerate formation. Conclusion: Even though the classic complications of external lengthening are virtually diminished, alterations to the current design of the ISKD are needed to avoid the distraction- related complications. Risk of unplanned surgery could be minimized through proper patient selection and proper surgical techniques

Blue Biotechnology : Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition

The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (M-pro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target M-pro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 M-pro inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as M-pro inhibitors with Delta G(binding) &lt; -33.0 kcal/mol. Binding energy and structural analyses of the most potent Sarcophyton inhibitor, bislatumlide A (340), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that 340 has a higher binding affinity against M-pro than darunavir with Delta G(binding) values of -43.8 and -34.8 kcal/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for 340; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that 340 has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of 340 as an antiviral agent against SARS-CoV-2

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy.

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients' primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

AbstractDevelopmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.</jats:p

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy