Application of Design of Experiments® Approach-Driven Artificial Intelligence and Machine Learning for Systematic Optimization of Reverse Phase High Performance Liquid Chromatography Method to Analyze Simultaneously Two Drugs (Cyclosporin A and Etodolac) in Solution, Human Plasma, Nanocapsules, and Emulsions.

The objectives of current investigation are (1) to find out wavelength of maximum absorbance (λ) for combined cyclosporin A and etodolac solution followed by selection of mobile phase suitable for the RP-HPLC method, (2) to define analytical target profile and critical analytical attributes (CAAs) for the analytical quality by design, (3) to screen critical method parameters with the help of full factorial design followed by optimization with face-centered central composite design (CCD) approach-driven artificial neural network (ANN)-linked with the Levenberg-Marquardt (LM) algorithm for finding the RP-HPLC conditions, (4) to perform validation of analytical procedures (trueness, linearity, precision, robustness, specificity and sensitivity) using combined drug solution, and (5) to determine drug entrapment efficiency value in dual drug-loaded nanocapsules/emulsions, percentage recovery value in human plasma spiked with two drugs and solution state stability analysis at different stress conditions for substantiating the double-stage systematically optimized RP-HPLC method conditions. Through isobestic point and scouting step, 205 nm and ACN:HO mixture (74:26) were selected respectively as the λ and mobile phase. The ANN topology (3:10:4) indicating the input, hidden and output layers were generated by taking the 20 trials produced from the face-centered CCD model.

Pathomechanisms of ALS8: altered autophagy and defective RNA binding protein (RBP) homeostasis due to the VAPB P56S mutation.

Mutations in RNA binding proteins (RBPs) and in genes regulating autophagy are frequent causes of familial amyotrophic lateral sclerosis (fALS). The P56S mutation in vesicle-associated membrane protein-associated protein B (VAPB) leads to fALS (ALS8) and spinal muscular atrophy (SMA). While VAPB is primarily involved in the unfolded protein response (UPR), vesicular trafficking and in initial steps of the autophagy pathway, the effect of mutant P56S-VAPB on autophagy regulation in connection with RBP homeostasis has not been explored yet.

A transfer learning with structured filter pruning approach for improved breast cancer classification on point-of-care devices.

Background And Objective: A significant progress has been made in automated medical diagnosis with the advent of deep learning methods in recent years. However, deploying a deep learning model for mobile and small-scale, low-cost devices is a major bottleneck. Further, breast cancer is more prevalent currently, and ductal carcinoma being its most common type.

Elliptic Flow of Electrons from Beauty-Hadron Decays in Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

The elliptic flow of electrons from beauty hadron decays at midrapidity (|y|<0.8) is measured in Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV with the ALICE detector at the LHC.

Role of microbes in the pathogenesis of neuropsychiatric disorders.

Microbes inhabit different anatomical sites of the human body including oral cavity, gut, and skin. A growing literature highlights how microbiome variation is associated with human health and disease. There is strong evidence of bidirectional communication between gut and brain mediated by neurotransmitters and microbial metabolites.

Size, microhabitat, and loss of larval feeding drive cranial diversification in frogs.

Habitat is one of the most important factors shaping organismal morphology, but it may vary across life history stages. Ontogenetic shifts in ecology may introduce antagonistic selection that constrains adult phenotype, particularly with ecologically distinct developmental phases such as the free-living, feeding larval stage of many frogs (Lissamphibia: Anura). We test the relative influences of developmental and ecological factors on the diversification of adult skull morphology with a detailed analysis of 15 individual cranial regions across 173 anuran species, representing every extant family.

The evolution of mammalian brain size.

Relative brain size has long been considered a reflection of cognitive capacities and has played a fundamental role in developing core theories in the life sciences. Yet, the notion that relative brain size validly represents selection on brain size relies on the untested assumptions that brain-body allometry is restrained to a stable scaling relationship across species and that any deviation from this slope is due to selection on brain size. Using the largest fossil and extant dataset yet assembled, we find that shifts in allometric slope underpin major transitions in mammalian evolution and are often primarily characterized by marked changes in body size.

A Study on Acute Membranous Tonsillitis, Its Different Etiologies and Its Clinical Presentation in a Tertiary Referral Centre.

Membranous tonsillitis is the infection of the palatine tonsils where the exudation from the crypts coalesce to form a membrane over the tonsillar surface. It is a stage ahead of the acute follicular tonsillitis. There are different etiologies for membrane formation over the tonsils.

Functional constraints during development limit jaw shape evolution in marsupials.

Differences in jaw function experienced through ontogeny can have striking consequences for evolutionary outcomes, as has been suggested for the major clades of mammals. By contrast to placentals, marsupial newborns have an accelerated development of the head and forelimbs, allowing them to crawl to the mother's teats to suckle within just a few weeks of conception. The different functional requirements that marsupial newborns experience in early postnatal development have been hypothesized to have constrained their morphological diversification relative to placentals.

A hybrid topological and shape-matching approach for structure analysis.

Properties of crystalline and amorphous materials are characterized by the underlying long-range and local crystalline order. Deformations and defects are structural hallmarks of plasticity, ice formation, and crystal growth mechanisms. Partitioning topological networks into constituent crystal building blocks, which is the basis of topological identification criteria, is an intuitive approach for classification in both bulk and confinement.

A serum microRNA sequence reveals fragile X protein pathology in amyotrophic lateral sclerosis.

Knowledge about converging disease mechanisms in the heterogeneous syndrome amyotrophic lateral sclerosis (ALS) is rare, but may lead to therapies effective in most ALS cases. Previously, we identified serum microRNAs downregulated in familial ALS, the majority of sporadic ALS patients, but also in presymptomatic mutation carriers. A 5-nucleotide sequence motif (GDCGG; D = G, A or U) was strongly enriched in these ALS-related microRNAs.

Controlling magnetoresistance by tuning semimetallicity through dimensional confinement and heteroepitaxy.

Controlling electronic properties via band structure engineering is at the heart of modern semiconductor devices. Here, we extend this concept to semimetals where, using LuSb as a model system, we show that quantum confinement lifts carrier compensation and differentially affects the mobility of the electron and hole-like carriers resulting in a strong modification in its large, nonsaturating magnetoresistance behavior. Bonding mismatch at the heteroepitaxial interface of a semimetal (LuSb) and a semiconductor (GaSb) leads to the emergence of a two-dimensional, interfacial hole gas.

Peak Blood Lactate Concentration and Its Arrival Time Following Different Track Running Events in Under-20 Male Track Athletes.

Purpose: To determine (1) the time of arrival of peak blood lactate concentration ([BLa]peak) followed by various track events and (2) significant correlation, if any, between average velocity and [BLa]peak in these events.

Methods: In 58 under-20 male track athletes, heart rate was recorded continuously and blood lactate concentration was determined at various intervals following 100-m (n = 9), 200-m (n = 8), 400-m (flat) (n = 9), 400-m hurdles (n = 8), 800-m (n = 9), 1500-m (n = 8), 3000-m steeplechase (n = 7), and 5000-m (n = 10) runs.

Results: The [BLa]peak, in mmol/L, was recorded highest following the 400-m run (18.

The Intertwined Evolution and Development of Sutures and Cranial Morphology.

Phenotypic variation across mammals is extensive and reflects their ecological diversification into a remarkable range of habitats on every continent and in every ocean. The skull performs many functions to enable each species to thrive within its unique ecological niche, from prey acquisition, feeding, sensory capture (supporting vision and hearing) to brain protection. Diversity of skull function is reflected by its complex and highly variable morphology.

Combatting intracellular pathogens using bacteriophage delivery.

Intracellular pathogens reside in specialised compartments within the host cells restricting the access of antibiotics. Insufficient intracellular delivery of antibiotics along with several other resistance mechanisms weaken the efficacy of current therapies. An alternative to antibiotic therapy could be bacteriophage (phage) therapy.

Testing hypotheses of marsupial brain size variation using phylogenetic multiple imputations and a Bayesian comparative framework.

Considerable controversy exists about which hypotheses and variables best explain mammalian brain size variation. We use a new, high-coverage dataset of marsupial brain and body sizes, and the first phylogenetically imputed full datasets of 16 predictor variables, to model the prevalent hypotheses explaining brain size evolution using phylogenetically corrected Bayesian generalized linear mixed-effects modelling. Despite this comprehensive analysis, litter size emerges as the only significant predictor.

Inhibition of astrocyte hemichannel improves recovery from spinal cord injury.

Spinal cord injury (SCI) causes severe disability, and the current inability to restore function to the damaged spinal cord leads to lasting detrimental consequences to patients. One strategy to reduce SCI morbidity involves limiting the spread of secondary damage after injury. Previous studies have shown that connexin 43 (Cx43), a gap junction protein richly expressed in spinal cord astrocytes, is a potential mediator of secondary damage.

Kinome analyses of Candida albicans, C. parapsilosis and C. tropicalis enable novel kinases as therapeutic drug targets in candidiasis.

Candida spp. have attracted considerable attention as they cause serious human diseases in immunocompromised individuals. The genomes of the pathogenic Candida spp.

Otorhinolaryngological Manifestations and Its Management in COVID 19 Patients.

COVID 19 pandemic is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The first case was identified in December 2019, in Wuhan, China. It is an infectious disease and has led to the ongoing global pandemic.

Identification and structural characterization of potential degraded impurities of ribociclib by time of flight -tandem mass spectrometry, and their toxicity prediction.

The US FDA and EMA approved Ribociclib (RIBO) to treat metastatic breast cancers in 2017. Formation of impurities during storage of any drug can significantly contribute to its overall toxicity and therapeutic efficacy, which ultimately leads to a safety concern. Over the period, it has been observed that impurities sometimes cause serious unwanted toxicity, which can even lead to withdrawal of a drug from market.

as New Hotspot Mutation for Breast Cancer in Indian Population and Has a Role in DNA Damage and Repair in Mammalian Cells.

Breast cancer has replaced cervical cancer as being the most common and having the highest mortality among women in India. gene is conserved among organisms during evolutionary succession and is a member of LEM family proteins in lower metazoans and is involved in critical functions in the nuclear architecture, gene expression and cell signaling. is the human orthologous of LEM-3 and is involved in DNA damage response and DNA repair.

Orally Administered Drug Solubility-Enhancing Formulations: Lesson Learnt from Optimum Solubility-Permeability Balance.

Although oral drug delivery is considered as most acceptable route for administering the active pharmaceutical ingredients to patients of all age-groups with the exceptions of bed-ridden patients and infants, the extent and rate of drug reaching the systemic circulation (in other word, drug bioavailability) always depends on many factors such as drug solubility in gastrointestinal fluids and drug permeation into intraluminal epithelial membrane structure, absence (fasting state) and presence (fed state) of food materials in the gastrointestinal tract, and individual variations in gastric emptying time. Taking the most influential factors like drug solubility and its permeability into consideration, these two factors play a pivotal role and even act as the litmus test for the formulation scientists who involve in oral dosage form development. It is very clear that there should be an optimum solubility and permeability balance to be reachable for getting the desired drug bioavailability to exert the intended therapeutic activity.