The increasing prevalence of network connections is driving a continuous surge in the requirement for network security and safeguarding against cyberattacks. This has triggered the need to develop and implement intrusion detection systems (IDS), one of the key components of network perimeter aimed at thwarting and alleviating the issues presented by network invaders. Over time, intrusion detection systems have been instrumental in identifying network breaches and deviations.
View Article and Find Full Text PDFObjective: GPs have a complex role in obesity management due to patients' individualized experience of living with obesity, coupled with the challenge to deliver healthcare messages in non-stigmatizing ways. This study aimed to explore who initiates the topic of weight and how weight was discussed in real-world GP-patient consultations.
Method: A multi-disciplinary team, including obesity lived experience experts, undertook a secondary data analysis of 43 Australian video recorded consultations and patient surveys from The Digital Library using descriptive content analysis.
Positron emission tomography (PET) is frequently used to obtain target occupancy (%TO) of central nervous system (CNS) drug candidates during clinical development. Obtaining %TO with PET can be particularly powerful when the %TO associated with efficacy is known for a protein target. Using the radiotracer [F]AV-133, the relationship between plasma concentration (PK) and %TO of NBI-750142, an experimental inhibitor of the vesicular monoamine transporter type 2 (VMAT2) was obtained in both nonhuman primate (NHP) and human.
View Article and Find Full Text PDFIntroduction: Diamond Blackfan anaemia (DBA) is a rare disorder characterized by failure of red blood cell production, congenital abnormalities and cancer predisposition, primarily caused by pathogenic germline variants in genes encoding ribosomal proteins.
Methods: We conducted a genotype-phenotype and outcome study of 121 patients with DBA spanning the 20-year history of the National Cancer Institute's Inherited Bone Marrow Failure Syndromes study. Patient phenotypes were compared by large versus small ribosomal protein genes, across genes with >5 cases (, , and ) and by type of pathogenic variants (hypomorphic versus null, large deletions versus others).
Importance: Telomere biology disorders (TBDs) are inherited cancer-prone bone marrow failure syndromes with differences in morbidity and mortality based on mode of inheritance.
Objective: To quantify cancer risks in TBDs by genetic subgroups.
Design, Setting, And Participants: This longitudinal cohort study of TBDs assessed cancer occurrences from 2002 through 2022.
Nitrate reductases play pivotal roles in nitrogen metabolism by leveraging the molybdopterin cofactor to facilitate the reduction of nitrate to nitrite. Periplasmic nitrate reductases (NapA) utilize nitrate as a terminal electron acceptor when oxygen is limiting, helping to drive anaerobic metabolism in bacteria. Despite extensive research into NapA homologs, open questions about the mechanism remain especially at the molecular level.
View Article and Find Full Text PDFPunch-marked coins (PMCs) are the oldest coins in India and among the most widely circulated globally, often found in hoards that highlight their extensive use. This study utilizes X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) to analyze the surface elemental composition and chemical properties of nine series (S-0 to S-VIII) of Janapada (S-0) and imperial PMCs (S-1 to S-VIII) dating from 600 to 200 BCE, housed in the Numismatic Society of India at BHU, Varanasi, based on the Gupta-Hardakar classification related to the PMCs. XRD results reveal four prominent diffraction peaks corresponding to metallic silver (Ag) in the face-centred cubic (fcc) phase, with a slight variation in d-spacing (∼ 0.
View Article and Find Full Text PDFPOLA2 encodes the accessory subunit of DNA polymerase α (polα)/primase, which is crucial for telomere C-strand fill-in. Incomplete fill-in of the C-rich telomeric strand after DNA replication has been proposed as a mechanism for Coats plus syndrome, a phenotype within the broader spectrum of telomere biology disorders (TBD). Coats plus syndrome has so far been associated with pathogenic variants in POT1, CTC1, and STN1.
View Article and Find Full Text PDFTelomere biology disorders (TBDs), caused by pathogenic germ line variants in telomere-related genes, present with multiorgan disease and a predisposition to cancer. Clonal hematopoiesis (CH) as a marker of cancer development and survival in TBDs is poorly understood. Here, we characterized the clonal landscape of a large cohort of 207 patients with TBD with a broad range of age and phenotype.
View Article and Find Full Text PDFBackground Vascular endothelial growth factor (VEGF) is a powerful mitogen for endothelial cells that promotes migration, proliferation, and tube formation necessary for the angiogenic development of new blood vessels. When VEGF increases significantly, it causes pathological angiogenesis and increased vascular permeability in eye conditions such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). These disorders have become important global sources of morbidity and have a substantial financial impact not only on the medical community but also on the patients.
View Article and Find Full Text PDFAccurately building 3D atomic structures from cryo-EM density maps is a crucial step in cryo-EM-based protein structure determination. Converting density maps into 3D atomic structures for proteins lacking accurate homologous or predicted structures as templates remains a significant challenge. Here, we introduce Cryo2Struct, a fully automated de novo cryo-EM structure modeling method.
View Article and Find Full Text PDFThe EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein-nucleic acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9-2.5 Å) resolution.
View Article and Find Full Text PDFFanconi anemia (FA) is an inherited bone marrow failure syndrome (IBMFS) characterized by pathogenic variants in the FA/BRCA DNA repair pathway genes. Individuals with FA have an elevated risk of developing myelodysplastic syndrome, acute myeloid leukemia, and solid tumors. Hematopoietic cell transplantation (HCT) is the most effective treatment for FA related bone marrow failure but can increase the risk of cancer development.
View Article and Find Full Text PDFThe effects of ligand binding on protein structures and their functions carry numerous implications for modern biomedical research and biotechnology development efforts such as drug discovery. Although several deep learning (DL) methods and benchmarks designed for protein-ligand docking have recently been introduced, to date no prior works have systematically studied the behavior of docking methods within the context of (1) using predicted (apo) protein structures for docking (e.g.
View Article and Find Full Text PDFPeriplasmic nitrate reductase NapA from Campylobacter jejuni (C. jejuni) contains a molybdenum cofactor (Moco) and a 4Fe-4S cluster and catalyzes the reduction of nitrate to nitrite. The reducing equivalent required for the catalysis is transferred from NapC → NapB → NapA.
View Article and Find Full Text PDFA 59-year-old male patient came to the outpatient department with complaints of left-sided hemicranial headache with drooping of the left upper eyelid (UL) for three days associated with difficulty in swallowing and deviation of the tongue. The patient had a history of vigorous coughing for the past 15 days for which he did not take any medications. He was thoroughly evaluated in the outpatient department and diagnosed with Horner's syndrome.
View Article and Find Full Text PDFThe advent of single-particle cryo-electron microscopy (cryo-EM) has brought forth a new era of structural biology, enabling the routine determination of large biological molecules and their complexes at atomic resolution. The high-resolution structures of biological macromolecules and their complexes significantly expedite biomedical research and drug discovery. However, automatically and accurately building atomic models from high-resolution cryo-EM density maps is still time-consuming and challenging when template-based models are unavailable.
View Article and Find Full Text PDFThis research aims to investigate the potential of utilizing pomegranate peel powder (PPP) as a natural preservative in muffin preparation. Pomegranate peel is a rich source of bioactive compounds, including phenolics, flavonoids, and tannins, which possess high antioxidant and antimicrobial properties. The In-Vitro antifungal activity of pomegranate peel powder (8% PPP), potassium sorbate (0.
View Article and Find Full Text PDFConstitutional heterozygous pathogenic variants in genes coding for some components of the Fanconi anemia-BRCA signaling pathway, which repairs DNA interstrand crosslinks, represent risk factors for common cancers, including breast, ovarian, pancreatic and prostate cancer. A high cancer risk is also a main clinical feature in patients with Fanconi anemia (FA), a rare condition characterized by bone marrow failure, endocrine and physical abnormalities. The mainly recessive condition is caused by germline pathogenic variants in one of 21 FA-BRCA pathway genes.
View Article and Find Full Text PDFSerpiginous choroiditis is a rare cause of posterior uveitis, included in the spectrum of white dot syndromes. It occurs as a result of an autoimmune process but could be associated with infections such as tuberculosis (TB) (serpiginous-like choroiditis). Tubercular serpiginous-like choroiditis is more commonly reported in Southeast Asian countries than in Western countries.
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