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Structural understanding of 5-(4-hydroxy-phenyl)-N-(2-(5-methoxy-1H-indol-3-yl)-ethyl)-3-oxopentanamide as a neuroprotectant for Alzheimer's disease.

Bioorg Med Chem Lett 2021 May 5:128081. Epub 2021 May 5.

Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia, USA. Electronic address:

In our continuing efforts to develop novel neuroprotectants for Alzheimer's disease (AD), a series of analogs based on a lead compound that was recently shown to target the mitochondrial complex I were designed, synthesized and biologically characterized to understand the structure features that are important for neuroprotective activities. The results from a cellular AD model highlighted the important roles of the 4-OH on the phenyl ring and the 5-OCH on the indole ring of the lead compound. The results also demonstrated that the β-keto moiety can be modified to retain or improve the neuroprotective activity. Read More

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Validation of the Bath CRPS Body Perception Disturbance Scale.

J Pain 2021 May 5. Epub 2021 May 5.

Department of Psychology, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom; Centre for Pain Research, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom.

The Bath Complex Regional Pain Syndrome Body Perception Disturbance Scale ("B-CRPS-BPDS") measures alterations in body perception. We assessed its internal consistency, known group validity, construct validity, and associations with demographic and clinical characteristics. We also evaluated changes in, and baseline predictors of B-CRPS-BPDS scores at follow-up. Read More

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Morphological and transcriptomic alterations in neonatal lamb testes following developmental exposure to low-level environmental chemical mixture.

Environ Toxicol Pharmacol 2021 May 5:103670. Epub 2021 May 5.

School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK. Electronic address:

Exposure to anthropogenic environmental chemical mixtures could be contributing to the decline in male reproductive health. This study used the biosolid treated pasture (BTP) sheep model to assess the effects of exposure to low-dose chemical mixtures. Maternal BTP exposure was associated with lower plasma testosterone concentrations, a greater proportion of Sertoli cell-only seminiferous tubules, and fewer gonocytes in the testes of neonatal offspring. Read More

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Fortifying Wellbeing: How Chinese Consumers and Doctors Navigate the Role of Functional Foods.

Appetite 2021 May 5:105296. Epub 2021 May 5.

Department of Marketing, Business School, University of Auckland, 12 Grafton Rd, Auckland, 1142, New Zealand. Electronic address:

China's rapidly developing economy has seen an increase in medical problems commonly associated with affluent lifestyles such as increases in metabolic diseases and digestive issues. One response to this problem is an increase in the amount of functional foods currently available, which may take a Western food form, or be more closely associated with traditional Chinese medicine (TCM). This research seeks to understand how functional food and wellbeing intersect in order to better understand how consumers perceive the complex construct of wellbeing, and their agency in its creation. Read More

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Establishing the Minimal Clinically Important Difference and Patient-Acceptable Symptomatic State after Arthroscopic Meniscal Repair and Associated Variables for Achievement.

Arthroscopy 2021 May 5. Epub 2021 May 5.

Rush University Medical Center Department of Orthopedic Surgery, Chicago, IL, USA. Electronic address:

Purpose: The purpose of this study is to establish the minimal clinically important difference (MCID) and patient-acceptable symptomatic state (PASS) after arthroscopic meniscal repair and identify the factors associated with achieving these outcomes.

Methods: This is a retrospective study with prospectively collected data. Patient-reported outcome measures (PROMs) were collected from April 2017 to March 2020. Read More

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Chromatin remodelling complexes in cerebral cortex development and neurodevelopmental disorders.

Neurochem Int 2021 May 5:105055. Epub 2021 May 5.

Brain Development and Disease Mechanisms, Institute for Stem, Cell Science and Regenerative Medicine (inStem), Bangalore, India; Medicine, Bangalore Life Science Cluster, GKVK Post, Bellary, Road, Bangalore, 560065 INDIA. Electronic address:

The diverse number of neurons in the cerebral cortex are generated during development by neural stem cells lining the ventricle, and they continue maturing postnatally. Dynamic chromatin regulation in these neural stem cells is a fundamental determinant of the emerging property of the functional neural network, and the chromatin remodellers are critical determinants of this process. Chromatin remodellers participate in several steps of this process from proliferation, differentiation, migration leading to complex network formation which forms the basis of higher-order functions of cognition and behaviour. Read More

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XRCC2 repairs mitochondrial DNA damage and fuels malignant behavior in hepatocellular carcinoma.

Cancer Lett 2021 May 5. Epub 2021 May 5.

Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

The effects of DNA damage repair (DDR) and mitochondrial dysfunction associated with HCC have been investigated, but the functional role of mitochondrial DDR in HCC remains elusive. We studied the DDR genes and identified XRCC2 as a potential prognostic marker for HCC. XRCC2 overexpression was detected in HCC cells and shown to promote the malignant behavior of cancer cells. Read More

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A Literature Overview on Epilepsy and Inflammasome Activation.

Brain Res Bull 2021 May 5. Epub 2021 May 5.

CNR Neuroscience Institute, Milan, Italy.

Epilepsy is one of the most prevalent serious brain disorders worldwide. Accumulating evidence has suggested that inflammation participates in the progression and pathogenesis of epilepsy. During inflammation, a cytosolic multimolecular complex called the "inflammasome" is activated, driving the innate immune response. Read More

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Three-dimensional printing of gastro-floating tablets using polyethylene glycol diacrylate-based photocurable printing material.

Int J Pharm 2021 May 5:120674. Epub 2021 May 5.

College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.

Extruded three-dimensional (3D) printing based on photocurable materials has shown good application prospects in the medical field. This has been attributed to the operational aspect that can be performed at room temperature and the high mechanical strength of the extrudate and final product. However, the commonly used photocurable polymer, polyethylene glycol diacrylate (PEGDA), has a low viscosity and exhibits a long crosslinking time. Read More

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Trichinella spiralis excretory-secretory products downregulate MMP-9 in Dark Agouti rats affected by experimental autoimmune encephalomyelitis.

Exp Parasitol 2021 May 5:108112. Epub 2021 May 5.

Institute for the Application of Nuclear Energy INEP, University of Belgrade, Banatska 31b, 11080, Belgrade, Serbia.

Matrix metalloproteinases (MMPs), are implicated in the pathogenesis of multiple sclerosis (MS) and in its animal model, experimental autoimmune encephalomyelitis (EAE). Our aim was to investigate whether amelioration of EAE in Dark Agouti (DA) rats, induced by Trichinella spiralis muscle larvae excretory-secretory products (ES L1), could be related to the level and activity of gelatinases, MMP-9 and MMP-2. Serum levels of MMP-9, MMP-2, NGAL/MMP-9, TIMP-1, and cytokines, evaluated by gel-zymography or ELISA, as well as gelatinases and TIMP-1 expression in the spinal cord (SC), were determined in: i) EAE induced, ii) ES L1-treated EAE induced animals. Read More

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Pediatric Asthma Incidence Rates in the United States from 1980-2017.

J Allergy Clin Immunol 2021 May 5. Epub 2021 May 5.

Background: Few studies have examined longitudinal asthma incidence rates from a public health surveillance perspective.

Objective: Calculate descriptive asthma incidence rates in children over time considering demographics and parental asthma history.

Methods: Data from nine US birth cohorts were pooled into one population covering 1980-2017. Read More

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Proton exit pathways surrounding the Oxygen Evolving Complex of Photosystem II.

Biochim Biophys Acta Bioenerg 2021 May 5:148446. Epub 2021 May 5.

Department of Chemistry, The Graduate Center, City University of New York, New York, NY 10016, United States; Department of Physics, City College of New York, New York 10031, United States; Department of Physics, The Graduate Center of the City University of New York, New York, NY 10016, United States. Electronic address:

Photosystem II allows water to be the primary electron source for the photosynthetic electron transfer chain. Water is oxidized to dioxygen at the Oxygen Evolving Complex (OEC), a MnCaO inorganic core embedded on the lumen side of PSII. Water-filled channels surrounding the OEC must bring in substrate water molecules, remove the substrate protons to the lumen, and may transport the product oxygen. Read More

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Imaging developmental cell cycles.

Biophys J 2021 May 5. Epub 2021 May 5.

Department of Molecular Biology, Princeton University. Princeton NJ, USA.

The last decade has seen a major expansion in development of live biosensors, the tools needed to genetically encode them into model organisms, and the microscopic techniques used to visualize them. When combined, these offer us powerful tools with which to make fundamental discoveries about complex biological processes. In this review we summarize the availability of biosensors to visualize an essential cellular process-the cell cycle-and the techniques for single cell tracking and quantification of these reporters. Read More

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Reversibility and Irreversibility in the Temperature Denaturation of Monoclonal Antibodies.

Anal Biochem 2021 May 5:114240. Epub 2021 May 5.

Department of Biology, Johns Hopkins University, 3400 North Charles, Baltimore, MD, 21218. Electronic address:

There have been numerous studies of the temperature denaturation of monoclonal antibodies (mAbs) using differential scanning calorimetry (DSC). In general, mAbs are characterized by complex temperature denaturation transitions in which the various domains (CH2, CH3, Fab) give rise to different peaks in the heat capacity function. The complexity and overall irreversibility of the temperature denaturation transition is well known and has limited the number of publications with an in-depth analysis of the data. Read More

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Parental genome unification is highly error-prone in mammalian embryos.

Cell 2021 Apr 30. Epub 2021 Apr 30.

Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany. Electronic address:

Most human embryos are aneuploid. Aneuploidy frequently arises during the early mitotic divisions of the embryo, but its origin remains elusive. Human zygotes that cluster their nucleoli at the pronuclear interface are thought to be more likely to develop into healthy euploid embryos. Read More

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Leveraging both individual-level genetic data and GWAS summary statistics increases polygenic prediction.

Am J Hum Genet 2021 Apr 30. Epub 2021 Apr 30.

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8210 Aarhus V, Denmark; National Centre for Register-Based Research, Aarhus University, 8210 Aarhus V, Denmark; Bioinformatics Research Centre, Aarhus University, 8000 Aarhus C, Denmark. Electronic address:

The accuracy of polygenic risk scores (PRSs) to predict complex diseases increases with the training sample size. PRSs are generally derived based on summary statistics from large meta-analyses of multiple genome-wide association studies (GWASs). However, it is now common for researchers to have access to large individual-level data as well, such as the UK Biobank data. Read More

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A mutation in SLC37A4 causes a dominantly inherited congenital disorder of glycosylation characterized by liver dysfunction.

Am J Hum Genet 2021 May 4. Epub 2021 May 4.

Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.

SLC37A4 encodes an endoplasmic reticulum (ER)-localized multitransmembrane protein required for transporting glucose-6-phosphate (Glc-6P) into the ER. Once transported into the ER, Glc-6P is subsequently hydrolyzed by tissue-specific phosphatases to glucose and inorganic phosphate during times of glucose depletion. Pathogenic variants in SLC37A4 cause an established recessive disorder known as glycogen storage disorder 1b characterized by liver and kidney dysfunction with neutropenia. Read More

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WNK1 is an assembly factor for the human ER membrane protein complex.

Mol Cell 2021 Apr 30. Epub 2021 Apr 30.

Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125, USA. Electronic address:

The assembly of nascent proteins into multi-subunit complexes is a tightly regulated process that must occur at high fidelity to maintain cellular homeostasis. The ER membrane protein complex (EMC) is an essential insertase that requires seven membrane-spanning and two soluble cytosolic subunits to function. Here, we show that the kinase with no lysine 1 (WNK1), known for its role in hypertension and neuropathy, functions as an assembly factor for the human EMC. Read More

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Gene Flow Increases Phylogenetic Structure and Inflates Cryptic Species Estimations: A Case Study on Widespread Philippine Puddle Frogs (Occidozyga laevis).

Syst Biol 2021 May 8. Epub 2021 May 8.

Biodiversity Institute and Department of Ecology and Evolutionary Biology, University of Kansas, Lawrence, KS 66045, USA.

In cryptic amphibian complexes, there is a growing trend to equate high levels of genetic structure with hidden cryptic species diversity. Typically, phylogenetic structure and distance-based approaches are used to demonstrate the distinctness of clades and justify the recognition of new cryptic species. However, this approach does not account for gene flow, spatial, and environmental processes that can obfuscate phylogenetic inference and bias species delimitation. Read More

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Fossil-informed models reveal a Boreotropical origin and divergent evolutionary trajectories in the walnut family (Juglandaceae).

Syst Biol 2021 May 8. Epub 2021 May 8.

Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland.

Temperate woody plants in the Northern Hemisphere have long been known to exhibit high species richness in East Asia and North America and significantly lower diversity in Europe, but the causes of this pattern remain debated. Here, we quantify the roles of dispersal, niche evolution, and extinction in shaping the geographic diversity of the temperate woody plant family Juglandaceae (walnuts and their relatives). Integrating evidence from molecular, morphological, fossil, and (paleo)environmental data, we find strong support for a Boreotropical origin of the family with contrasting evolutionary trajectories between the temperate subfamily Juglandoideae and the tropical subfamily Engelhardioideae. Read More

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Back to the future: Reintegrating biology to understand how past eco-evolutionary change can predict future outcomes.

Integr Comp Biol 2021 May 8. Epub 2021 May 8.

Department of Plant and Microbial Biology, University of Minnesota,

During the last few decades, biologists have made remarkable progress in understanding the fundamental processes that shape life. But despite the unprecedented level of knowledge now available, large gaps still remain in our understanding of the complex interplay of eco-evolutionary mechanisms across scales of life. Rapidly changing environments on Earth provide a pressing need to understand the potential implications of eco-evolutionary dynamics, which can be achieved by improving existing eco-evolutionary models and fostering convergence among the sub-fields of biology. Read More

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Mechanical and in vitro biological properties of uniform and graded Cobalt-chrome lattice structures in orthopedic implants.

J Biomed Mater Res B Appl Biomater 2021 May 8. Epub 2021 May 8.

Movement Analysis Laboratory, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.

Human bones are biological examples of functionally graded lattice capable to withstand large in vivo loading and allowing optimal stress distribution. Disruption of bone integrity may require biocompatible implants capable to restore the original bone structure and properties. This study aimed at comparing mechanical properties and biological behavior in vitro of uniform (POR-FIX) and graded (POR-VAR) Cobalt-chrome alloy lattice structures manufactured via Selective Laser Melting. Read More

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Property modelling of lysozyme-crosslinker-alginate complexes using latent variable methods.

J Biomed Mater Res A 2021 May 8. Epub 2021 May 8.

Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada.

Statistical methods were used to provide insight into a polymer complex system composed of lysozyme and alginate to quantify the effects of such parameters as pH, and ionic composition of the mixing solution on the properties of the complexes including composition, particle diameter, and zeta potential. Various crosslinkers (calcium, barium, iron[III], and bovine serum albumin), were used with lysozyme for complex formation to investigate the effect of crosslinker charge density on protein release kinetics, modelled using kt . Multivariate statistical analysis showed that the kinetic parameters associated with the release were, not surprisingly highly dependent on the ionic strength of the release media, with higher ionic strength leading to faster release. Read More

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Investigation of water-insoluble hydrophobic polyethylenimines as RNAi vehicles in chronic myeloid leukemia therapy.

J Biomed Mater Res A 2021 May 8. Epub 2021 May 8.

Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Canada.

The discovery of RNA interference (RNAi) more than two decades ago opened avenues for avant-garde cancer treatments that possess the ability to evade issues hampering current chemotherapeutic strategies, owing to its specific gene sequence-driven mechanism of action. A potent short interfering RNA (siRNA) delivery vehicle designed to overcome physiological barriers is imperative for successful RNAi therapy. For this purpose, this study explored the characteristics and therapeutic efficacy of low-molecular weight (MW) polyethylenimine (PEI) with high cholesterol substitution, yielding water-insoluble polymers, in chronic myeloid leukemia (CML) K562 cells. Read More

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Identifying loci under selection via explicit demographic models.

Mol Ecol Resour 2021 May 8. Epub 2021 May 8.

Department of Biology, University of Fribourg, Fribourg, Switzerland.

Adaptive genetic variation is a function of both selective and neutral forces. To accurately identify adaptive loci, it is thus critical to account for demographic history. Theory suggests that signatures of selection can be inferred using the coalescent, following the premise that genealogies of selected loci deviate from neutral expectations. Read More

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Functional Link Convolutional Neural Network for the Classification of Diabetes Mellitus.

Int J Numer Method Biomed Eng 2021 May 8:e3496. Epub 2021 May 8.

Dept. of Computer Science and Engineering, Bennett University, Noida, Uttar Pradesh, India.

Diabetes is a faction of metabolic ailments distinguished by hyperglycemia which is the consequence of a defect ,in the action of insulin, insulin secretion, or both and producing various abnormalities in the human body. In recent years, the utilization of intelligent systems has been expanded in disease classification and numerous researches have been proposed. In this research article, a variant of Convolutional Neural Network i. Read More

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Extremely preterm infants experienced good comfort with various nasal respiratory support techniques delivered with masks.

Acta Paediatr 2021 May 8. Epub 2021 May 8.

Division of Paediatrics and Neonatal Critical Care, A.Béclère Medical Centre, Paris Saclay University Hospitals, France.

Extremely preterm neonates often need ongoing support for chronic pulmonary insufficiency of prematurity. The simplest support is continuous positive airway pressure (CPAP). More complex techniques are bilevel positive airway pressure (BiPAP), non-invasive positive pressure ventilation (NIPPV) and non-invasive high-frequency oscillatory ventilation (NHFOV). Read More

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Identification of PDHX as a metabolic target for esophageal squamous cell carcinoma.

Cancer Sci 2021 May 8. Epub 2021 May 8.

Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

The metabolism in tumors is reprogrammed to meet its energetic and substrate demands. However, this metabolic reprogramming creates the metabolic vulnerabilities, providing new opportunities for cancer therapy. Metabolic vulnerability as a therapeutic target in esophageal squamous cell carcinoma (ESCC) has not been adequately clarified. Read More

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Reasons for physician-related variability in end-of-life decision-making in intensive care.

Acta Anaesthesiol Scand 2021 May 8. Epub 2021 May 8.

Department of Anesthesiology and Intensive Care, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Background: There is increasing evidence that the individual physician is the main factor influencing variability in end-of-life decision-making in intensive care units. End-of-life decisions are complex and should be adapted to each patient. Physician-related variability is problematic as it may result in unequal assessments that affect patient outcomes. Read More

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The Bariatric-Metabolic Physician's Role in Managing Clinically Severe Obesity.

Curr Obes Rep 2021 May 8. Epub 2021 May 8.

Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Purpose Of Review: The aim of this review is to outline the obesity physician's role in managing patients with severe obesity with a particular emphasis on bariatric surgery candidates.

Recent Findings: Obesity is a chronic, relapsing and progressive disease. Scoring systems that evaluate the severity of obesity based on the clinical assessment, rather than the Body Mass Index, are a valuable tool. Read More

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