bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical Chemistry
Authors: Evans E. Hywel , Foulkes Mike E.
Published: September 2023

Analytical Chemistry starts by defining the analytical approach in terms of a framework for dealing with problems. It then looks at sampling. The chapter that follows is about sample preparation. The text moves on after that to look at instrument measurement techniques. There follows a chapter on calibration and quantitation. The text also considers reference materials and standards. Next, it looks at sampling error. Finally, the book considers method validation and quality assurance.
Basic statistics
Authors: Evans E. Hywel , Foulkes Mike E.
Published: September 2023

This chapter analyses a range of methods to display analytical data and basic statistical concepts. It explains how to use a t-test to compare a mean with a true value. It shows how to make a comparison of two means and how to utilize appropriate statistical tests and graphical methods to evaluate and interpret analytical data in a variety of contexts. It also discusses a way of comparing measurements to support any decisions made by using statistics. It examines studying the data visually. The chapter highlights the use of blob plots for small datasets of up to ten data points on a horizontal scale. It mentions histograms for large datasets, wherein the vertical axis gives the number of results that fall within a small defined range on the horizontal measurement scale.
Kidney and urinary tract
Authors: Orchard Guy , Muskett David , Nation Brian
Published: September 2023

This chapter highlights the cells of the kidney and urinary tract. The kidneys and urinary system provide the basis for homeostatic regulation of the body's water level, controlling electrolytes and fluid balance. The kidneys operate by a series of active and passive transport mechanisms to ensure efficient production of urine. They have numerous hormonal functions; for example, controlling blood pressure through the renin-angiotensin function, the production of red blood cells via the production of erythropoietin, processing vitamin D, and the production of antihypertensive lipids. The urinary system comprises two kidneys, two ureters, the bladder, and a single draining urethra. Anatomically, the kidneys are located on the posterior wall of the abdomen at around waist height. The chapter also looks at urinary system disease and kidney transplantation.
Reproductive cells and gametogenesis
Authors: Evered Andrew , Shambayati Behdad
Published: September 2023

This chapter reviews the cells and tissues that make up the reproductive tract. The reproductive system is unique in possessing a population of cells that contain half the amount of genetic material normally found in other cells of the body. These germ cells, or gametes as they are sometimes called, are created by a process known as gametogenesis and give humans their reproductive capacity. The chapter then looks at how the cells of the testes and associated duct system support spermatogenesis, as well as how the cells of the ovary and associated ducts and cavities support oogenesis. It also explains how the structure of spermatozoa and ova facilitates reproduction, before describing the structure and function of tissues that comprise the external genitalia.
Photosynthesis
Authors: Rehder Dieter
Published: September 2023

This chapter looks at the overall involvement of metal centres in photosynthesis, specifically discussing the central role of the chlorophylls on the one hand, and of the oxygen-evolving centre on the other hand. It first gives an overview of the Great Oxygenation Event which happened about 2.4 Ga ago, when photosynthetically active cyanobacteria, also called blue-green algae, started to produce — and to release into the atmosphere — more oxygen than could be eliminated by oxidation processes, such as oxidative decay of organics, or the conversion of ferrous to ferric iron, sulfide to sulfate, ammonia to nitrate, and so forth. This change forced organisms that failed to adapt to the novel situation into oxygen-free niches. Emphasizing that more than one hundred proteins are involved in the global regulation of the photosynthetic machinery, steering over 50 distinct chemical transformations, the chapter looks at relevant reaction pathways. Furthermore, it tackles artificial photosynthesis.
Cell Signalling
Authors: Hancock John T.
Published: September 2023

Cell Signalling provides an introduction to signalling within and between cells—one of the most important aspects of biochemistry and cell biology. It is composed of four parts, and Part 1 provides an overview of signalling and looks at the history and techniques of cell signalling. Part 2 considers components that comprise signalling pathways. For example, this part looks at extracellular signals, such as hormones, and discusses the detection of extracellular signals. Part 3 centres on selected examples of signalling pathways and events. These include insulin and the signal transduction cascades it invokes; perception of the environment; signalling in development and for the regulation of gene expression; and life, death, and apoptosis. The last part presents some final thoughts on cell signalling and looks to the future.
Thrive in Human Physiology
Authors: Kay Ian , Evans Gethin
Published: September 2023

Thrive in Human Physiology provides an initial introduction to human physiology. It then looks at control and co-ordination in terms of the nervous system and the endocrine system. It moves on to musculoskeletal physiology and movement, cardiovascular physiology, respiratory physiology, renal physiology, gastrointestinal physiology, reproductive physiology, and integrative physiology.
Molecular Biology of RNA
Authors: Elliott David , Ladomery Michael
Published: September 2023

Molecular Biology of RNA provides an overview of a cutting-edge field of biology. It starts with an introduction to the subject. It looks at how RNA can form versatile structures. It moves on to consider catalytic RNAs. Other topics covered include pre-mRNA splicing by the spliceosome, the RNA-binding proteins, pre-mRNA splicing defects found in development and disease, and co-transcriptional pre-mRNA processing. The text also looks at nucleocytoplasmic traffic of messenger RNA, messenger RNA localization, and translation of messenger RNA. It also examines stability and degradation of mRNA and RNA editing. Finally, the text provides an analysis on biogenesis and nucleocytoplasmic traffic of non-coding RNAs; the 'macro' RNAs, which include long non-coding RNAs and epigenetics; and the short non-coding RNAs and gene silencing. The text ends with a quick look at future perspectives.
Introduction to Molecular Biology of RNA
Authors: Elliott David , Ladomery Michael
Published: September 2023

This chapter provides an overview of the biochemical properties of RNA, including the versatility of its structure that enables a multitude of RNA molecules and functions in cells. It describes different types of RNA-binding domains that have evolved, and the co-transcriptional processes of capping and pre-mRNA splicing, cleavage, and polyadenylation. It also discusses the process of alternative splicing, which is a major generator of proteomic diversity. The chapter covers the processes of RNA editing, nucleocytoplasmic traffic, mRNA localization, translation, stability, decay, and rRNA and tRNA processing. It also gives a historical perspective in explaining the roles of pioneering scientists in some of the key discoveries in molecular biology.
The nature of pericyclic reactions
Authors: Ian Fleming
Published: September 2023

This chapter describes pericyclic reactions. These reactions are a third distinct class and have cyclic transition structures in which all bond-forming and bond-breaking takes place in concert. The chapter discusses the three classifications of organic reaction—ionic, radical, and pericyclic—and analyses ionic reactions which involve pairs of electrons that move in one direction. It also mentions the unimolecular reaction, wherein the carbon–halogen bond cleaves with both electrons going to the chloride ion and leaves an electron deficiency behind on the carbocation. The chapter describes the nucleophile, which provides both electrons for a new bond, in contrast to the electrophile, which receives them. It covers radical reactions that involve the correlated movement of single electrons..
Rotational and vibrational spectroscopy
Authors: Duckett Simon , Gilbert Bruce , Cockett Martin
Published: September 2023

This chapter presents a brief introduction to rotational and vibrational spectroscopy. It explains how pure rotational spectroscopy can be used in the precise determination of molecular geometry in small molecules and provide a direct means to deduce the shape of larger molecules. It also looks at how vibrational spectroscopy can be used in the measurement of geometrical parameters of gas phase molecules and in providing information about the structure and shape of molecules in the condensed phase. The chapter discusses the important role vibrational spectroscopy plays in characterization and analysis in organic chemistry where it is used typically in tandem with mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. It analyses concepts on a molecular scale by exploring how light interacts with the energy levels associated with rotational and vibrational degrees of freedom.
Mass spectrometry
Authors: Duckett Simon , Gilbert Bruce , Cockett Martin
Published: September 2023

This chapter highlights the fundamental principles of mass spectrometry. It explains the use of this technique in the determination of molecular masses and formulae and the interpretation of fragmentation patterns as a means to the determination of structure. It also provides some examples of structural analysis that show how problems can be solved using the technique and approach of mass spectrometry. The chapter highlights spectra from unknown compounds, emphasizes the use of mass spectrometry, and provides complementary information about the molecules under investigation. It surveys the very wide range of structural and analytical applications of mass spectrometry across the chemical and biochemical sciences, focusing on its extreme sensitivity.
Conjugation, π-Electron Delocalization, and Aromaticity
Authors: Okuyama Tadashi , Maskill Howard
Published: September 2023

This chapter begins with a discussion on extended π bonds and the concept of conjugation. It stresses that the C=C double bond is made up of a σ bond and a π bond, and the characteristic chemical properties of ethene come mainly from the π bond. The chapter also highlights that two C=C double bonds separated by a single σ bond are also able to interact by sideways overlap of their π molecular orbitals or MOs (called a conjugative interaction) in a conjugated system. The chapter then introduces stabilization or delocalization energy. It investigates how constituent π and p orbitals of appropriate energy and symmetry within a molecule (or ion) interact to give the new MOs of a conjugated system, and how the conjugation can be described by resonance. Next, the chapter considers the electronic structure of benzene and the nature of aromaticity.
Organic Reactions and the Concept of Mechanism
Authors: Okuyama Tadashi , Maskill Howard
Published: September 2023

This chapter shows how the reorganization of chemical bonds as an organic molecule reacts can be related to transformations of the molecular orbitals involved. Chemical transformations involve the redistribution of valence electrons of the reactant molecules. The chapter looks at how this happens, arguing that this is a major aspect of what is called the reaction mechanism. The chapter also illustrates how the redistribution of valence electrons associated with a chemical transformation can be represented by curly arrows. It argues that the reorganization of bonds associated with an organic chemical reaction is not instantaneous. The chapter then describes the reaction profile which includes a representation of the rate of the reaction (the Gibbs energy of activation) and the feasibility of the reaction (the Gibbs energy of reaction). It concludes by investigating organic reaction mechanisms and the reversibility of reactions and equilibrium.
Polycyclic and Heterocyclic Aromatic Compounds
Authors: Okuyama Tadashi , Maskill Howard
Published: September 2023

This chapter describes the structures of polycyclic aromatic hydrocarbons. It shows that most polycyclic aromatic compounds consist of two or more benzenoid rings fused together but some contain non-benzenoid rings. The chapter also explicates the reactions of polycyclic aromatic compounds, noting some polycyclic aromatic compounds including benzopyrenes are carcinogenic. The chapter then moves to discuss the structures of aromatic heterocycles. It stresses that the most common heterocyclic compounds contain one or more of three heteroatoms (N, O, and S) in the ring, and may be saturated or unsaturated. The chemistry of saturated heterocycles is generally similar to that of their acyclic counterparts. Unsaturated heterocyclic compounds are numerous and many are based on five- and six-membered aromatic rings containing a heteroatom. Finally, it discusses the reactions of five-membered aromatic heterocycles: pyrrole, furan, and thiophene. It also reviews the reactions of pyridine and its derivatives as well as the synthesis of aromatic heterocycles.
Reactions involving Radicals
Authors: Okuyama Tadashi , Maskill Howard
Published: September 2023

This chapter outlines the formation of radicals by homolysis. It emphasizes that the mechanisms of radical reactions are quite different from those of polar reactions: most occur by radical chain mechanisms. The chapter then examines the stability of radicals and the radical chain reactions. It then shifts to emphasize that radical reactions are important in biology and medicine. Radicals are in fact all around us: a normal oxygen molecule is a diradical, reactive oxygen species such as superoxide anion, hydroperoxyl radical, and hydroxyl radical are believed to be implicated in the ageing process. Finally, the chapter examines radical polymerization. Radical polymerization is an important industrial process for the production of useful plastics. It then studies the formation of radical ions by single electron transfer, and their reactions as well as the electrolytic reactions.
Structural Determination of Organic Compounds
Authors: Okuyama Tadashi , Maskill Howard
Published: September 2023

This chapter looks at how molecular structure is determined. It shows the scope of each method so that, when faced with a structural problem, the most appropriate method for its solution can be identified. The chapter then argues that it is important that organic chemists understand the basis of each principal method they are likely to use for determining the molecular structures of organic compounds, especially ones they have prepared themselves. It also explains the interactions of electromagnetic radiation with molecules, and reviews ultraviolet and visible spectroscopy. The chapter then explains infrared spectroscopy and proton, and carbon nuclear magnetic resonance spectroscopy. It concludes by examining mass spectrometry.
Thrive in Genetics
Authors: Thomas Alison
Published: September 2023

Thrive in Genetics starts off by considering the following topics: chromosomes and cellular reproduction, the principles of Mendelian inheritance, and eukaryotic gene mapping. There are also chapters on quantitative genetics, the genetics of bacteria, viruses, and organelles. Therein follow chapters on the biochemical basis of heredity, genotypes, phenotype I, phenotype II, and how to control gene expression. There are also chapters on gene mutations, chromosome mutations, the genetics of populations, and working with genes.
Eukaryotic Gene Mapping
Authors: Thomas Alison
Published: September 2023

This chapter evaluates eukaryotic gene mapping, which is often a two-part process involving genetic and physical mapping. Genetic mapping uses traditional Mendelian analysis of carefully constructed genetic crosses to produce maps showing the relative positions of genes and other features on a chromosome; this analysis identifies approximate gene positions. Meanwhile, physical mapping employs molecular techniques, e.g. DNA sequencing, to directly examine the DNA of chromosomes to determine the precise position of genes. The chapter then looks at gene mapping using trihybrid crosses, before considering how human genes are mapped by examining pedigrees for the co-segregation of traits. It also studies how logarithm of odds (LOD) scores are calculated, using data from human pedigrees, to assess the likelihood of linkage of two genes.
The Biochemical Basis of Heredity
Authors: Thomas Alison
Published: September 2023

This chapter addresses the biochemical basis of heredity. Nucleotides, which polymerize to form long chains, are the building blocks of DNA and RNA. A DNA molecule consists of two chains of nucleotides coiled around each other to form a double helix, while an RNA molecule consists of a single chain. The DNA double helix is formed by complementary base pairing between nucleotides on opposite strands. During DNA replication, the two strands separate and each becomes a template for the synthesis of a new strand. The sequence of nucleotides encodes the genetic information. The chapter then looks at the types of DNA sequence as well as transposable elements.
DNA sequencing
Authors: Slatter Tania , Fitches Alison
Published: September 2023

This chapter looks at DNA sequencing, a technique used to determine the precise order of the nucleotide bases-adenine, guanine, cytosine, and thymine-in a DNA fragment. The chapter explains the first-generation sequencing methods: the chemical method introduced by Maxam and Gilbert in 1977, the Sanger dideoxy-chain-termination sequencing method, and the chain-termination cycle sequencing method. It also tackles the uses of next-generation sequencing methods which use newer technologies. The chapter gives an overview of the next-generation sequencing procedure and explains the template preparation. It describes the various sequencing platforms, namely, the Roche 454, Illumina system, and SOLiD system. The chapter also lists some bioinformatic tools for the analysis of next-generation sequencing data. Lastly, it discusses the limitations of next-generation sequencing.
Measuring DNA–protein interactions
Authors: Acevedo Luis , Sanz Ana , Labhart Paul , Jelinek Mary Anne
Published: September 2023

This chapter examines the commonly used methods for the analysis of DNA-protein interactions. It takes a closer look at DNA-binding proteins that regulate a variety of cellular processes including gene expression, replication, and recombination, and maintenance of genome integrity. Furthermore, the chapter explains DNA footprinting which enables the identification of the nucleotides that contact a DNA-binding protein. It also discusses the electrophoretic mobility shift assay (EMSA), also known as gel shift or gel retardation. The EMSA is another
in vitro
technique that can be used to analyse protein binding to a defined DNA sequence of interest. Lastly, it tackles the Chromatin ImmunoPrecipitation (ChIP) assay which allows
in vivo
identification of DNA sequences associated with proteins when the DNA is in its native chromatin state.
RNA interference technology
Authors: Hampson Ian , Batman Gavin , Walker Thomas
Published: September 2023

This chapter explains the RNA interference (RNAi) machinery that regulates post-transcriptional gene silencing. The RNAi technology is considered a vital tool in basic molecular and cellular genetic research, functional genomics, gene expression profiling, drug discovery, prospective disease targeting, and therapies. The chapter describes how the two main classes of small regulatory RNAs-short interfering RNA (siRNA) and microRNA (miRNA)-are generated and how they silence gene expression. It gives an overview of the RNAi pathway and looks at the two main approaches currently used to silence gene expression
in vitro
, namely, the siRNA technology and the short hairpin RNA (shRNA) technology. Moreover, it discusses the advantages and limitations of the two. The chapter also explores the therapeutic possibilities available using targeted gene silencing.
Recombinant protein expression
Authors: Harrison Michael , McPherson Michael J.
Published: September 2023

This chapter zooms in on technical issues related to the systems commonly used for recombinant protein production and discusses the advantages and disadvantages of each. Among these expression systems are E. coli, Lactobacillus lactis, Saccharomyces cerevisiae, Pichia pastoris, insect larval cells, mammalian cells, and cell-free systems. The chapter explains how recombinant proteins are made in the research laboratory using different prokaryotic and eukaryotic host cells and introduces currently available vector technologies for protein overexpression in bacterial, yeast, and insect larval cells. It describes the two types of complementary DNA delivery systems or vectors-the plasmids and engineered viruses. The chapter intends to guide the readers on how to choose the appropriate expression system depending on the type and source of protein that they are trying to produce and the purpose of production.
Protein purification
Authors: Manfield Iain
Published: September 2023

This chapter provides a comparison of the different chromatography methods used in protein purification. Chromatographic methods are techniques in which proteins are passed through a column packed with a stationary material. These include affinity chromatography which uses the ability of a target protein to bind to a specific ligand that is immobilized on a chromatography matrix; ion-exchange chromatography which uses charged groups attached to a matrix to capture proteins with regions of complementary charge; hydrophobic interaction chromatography which utilizes hydrophobic interactions between protein and matrix to bind protein under high salt concentration conditions; and size exclusion chromatography wherein a sample is passed through a porous matrix which excludes molecules of a particular size from entering the pores whilst smaller molecules penetrate the pores. The chapter also outlines the key factors to be considered in devising a protein purification strategy.
Mass spectrometry
Authors: Ault James R. , Ashcroft Alison E.
Published: September 2023

This chapter explains the use of mass spectrometry, an analytical technique for probing biomolecules. The chapter gives a closer look at the basic principles of how spectrometers work and how samples are prepared for analysis. It introduces the basic components of a mass spectrometer which are the ionization source, mass-to-charge analyser, and detector. It also describes electrospray ionization and matrix-assisted laser desorption ionization-the two ionization techniques recommended for the analysis of biomolecules. Moreover, it explores some of the applications of mass spectrometry in biomolecular research. The discussion in this chapter covers peptide sequencing, the study of non-covalent interactions in biomolecular complexes, and the detection of pharmaceutical products in river water.
Flow cytometry
Authors: Lawry John
Published: September 2023

This chapter focuses on flow cytometry, a powerful technique used for counting and sorting cells based on their size or protein expression. Flow cytometry uses laser technology to facilitate rapid and simultaneous multiple analyses from cells suspended in a fluid stream. The chapter first introduces major works in the 1950s which paved the way for the development of flow cytometers. It then describes how flow cytometers work, explaining their four components: fluidics, lasers, optics, and electronics. Furthermore, the chapter emphasizes the importance of sample preparation when using a flow cytometer. It also looks at how data are is presented in this technique and what thisthese means. Lastly, it describes the key applications of flow cytometry: immunophenotyping, cell cycle analysis, apoptosis, and viability. The discussion in this chapter also covers cell sorting, a unique feature of flow cytometers.
Mathematical models in biomolecular sciences
Authors: Athens Josie A.
Published: September 2023

This chapter explains the methods used in performing experiments
in silico
, meaning on the computer, to better understand a biological phenomenon. Computer simulations based on mathematical models allow the testing of new hypotheses; exploration of different theoretical scenarios and prediction of potential outcomes based on a particular set of assumptions; and estimation of biological parameters from experimental data. Equations that represent mathematical models are used to formally express the relationship between biological variables. The chapter delves into linear and non-linear difference equations, cellular automata, Markov chains, Petri nets, and ordinary differential equations. It emphasizes that the predictive power of a mathematical model depends mainly on the accuracy of its parameters, the underlying assumptions, its complexity, and its capability to fit experimental data.
Plant Systematics
Authors: Judd Walter S. , Campbell Christopher S. , Kellogg Elizabeth A. , Stevens Peter F. , Donoghue Michael J.
Published: September 2023

Plant Systematics begins by looking at the field of plant systematics as a whole. It then introduces methods and principles of biological systematics before turning to the historical background of classification and system in flowering plants. Next, it examines taxonomic evidence, including an outline of structural and biochemical characters. The text also discusses the evolution of plant diversity and provides an overview of green plant phylogeny. Finally, the book ends with an analysis of lycophytes, ferns, and gymnosperm, and phylogenetic relationships of angiosperms.
Biodiversity Concepts and Measurement
Authors: Cardinale Bradley J. , Primack Richard B. , Murdoch James D.
Published: September 2023

This chapter examines biodiversity concepts and measurement. Three common components of biodiversity are the focus of conservation efforts. Genetic diversity refers to the genetic variation within species, both among individuals within single populations and among geographically distinct populations. Meanwhile, species diversity refers to the variety of species that comprise a biological community—the collection of species that occupy and interact in a particular location. Community and ecosystem diversity refers to the different biological communities and their associated ecosystems that comprise whole landscapes. All three levels of biodiversity are necessary for the continued survival of life as we know it, and all are important to people. The chapter also looks at phylogenetic diversity.
Extinction
Authors: Cardinale Bradley J. , Primack Richard B. , Murdoch James D.
Published: September 2023

This chapter addresses global patterns of species endangerment and provides an overview of the primary drivers of extinction. It also describes local patterns of biodiversity change and details the key factors that control extinction risk. In order to track rates of global extinction, it is necessary to keep track of species that are known to have already gone extinct, along with the species that are presently threatened with extinction. The primary tool that conservation biologists use to keep track of the global status of extinct, threatened, and endangered species is the International Union for Conservation of Nature's (IUCN) Red List. The drivers of extinction include habitat loss, overexploitation, invasive alien species, and climate change.
Competition and Other Plant Interactions
Authors: Gurevitch Jessica , Scheiner Samuel M. , Fox Gordon A.
Published: September 2023

This chapter highlights plant competition: how plants compete with one another and how competition affects the survival and growth of individual plants within a population. Competition can be defined as a reduction in fitness of competing individuals due to shared use of a limiting resource. At the population level, this translates to a reduction in population growth rates. The chapter also details how plants' interactions with one another form a spectrum from negative to neutral to positive interactions. It reviews the methods for studying species interactions, then looks at the effects of competition and facilitation on populations, population distributions, and community composition. It is these aspects of competition that have been the subject of the greatest controversy. Towards the end, the chapter examines some of these debates and takes a look at the evidence ecologists have gathered on the role and importance of competition.
Community Dynamics and Succession
Authors: Gurevitch Jessica , Scheiner Samuel M. , Fox Gordon A.
Published: September 2023

This chapter analyzes patterns of community change and their causes. It explores a variety of other aspects of communities: their continuity in time, their predictability, and whether they reach an equilibrium. The chapter also discusses the process of succession and its importance to the study of plant communities. Succession is change in structure or composition of a group of organisms of different species at a site through time. The chapter then details the two types of change: cyclic change, such as that which occurs over the course of a year or in response to weather fluctuations, and longer-term community dynamics that may continue in a single direction. Next, the chapter explores the variation between disturbance and succession. It then demonstrates a number of different patterns, mechanisms, and causes involved in succession.
A common single nucleotide variant in the cytokine receptor-like factor-3 (CRLF3) gene causes neuronal deficits in human and mouse cells
Authors: Wilson Anna F , Barakat Rasha , Mu Rui , Karush Leah L , Gao Yunqing , Hartigan Kelly A , Chen Ji-Kang , Shu Hongjin , Turner Tychele N , Maloney Susan E , Mennerick Steven J , Gutmann David H , Anastasaki Corina
Published: September 2023

Single nucleotide variants in the general population are common genomic alterations, where the majority are presumed to be silent polymorphisms without known clinical significance. Using human induced pluripotent stem cell (hiPSC) cerebral organoid modeling of the 1.4 megabase Neurofibromatosis type 1 (NF1) deletion syndrome, we previously discovered that the cytokine receptor-like factor-3 (CRLF3) gene, which is co-deleted with the NF1 gene, functions as a major regulator of neuronal maturation. Moreover, children with NF1 and the CRLF3L389P variant have greater autism burden, suggesting that this gene might be important for neurologic function. To explore the functional consequences of this variant, we generated CRLF3L389P-mutant hiPSC lines and Crlf3L389P-mutant genetically engineered mice. While this variant does not impair protein expression, brain structure, or mouse behavior, CRLF3L389P-mutant human cerebral organoids and mouse brains exhibit impaired neuronal maturation and dendrite formation. In addition, Crlf3L389P-mutant mouse neurons have reduced dendrite lengths and branching, without any axonal deficits. Moreover, Crlf3L389P-mutant mouse hippocampal neurons have decreased firing rates and synaptic current amplitudes relative to wild type controls. Taken together, these findings establish the CRLF3L389P variant as functionally deleterious and suggest that it may be a neurodevelopmental disease modifier.
Cardiopulmonary bypass management and risk of new-onset atrial fibrillation after cardiac surgery
Authors: Taha Amar , Hjärpe Anders , Martinsson Andreas , Nielsen Susanne J , Barbu Mikael , Pivodic Aldina , Lannemyr Lukas , Bergfeldt Lennart , Jeppsson Anders
Published: September 2023

OBJECTIVES

Cardiopulmonary bypass (CPB) management may potentially play a role in the development of new-onset atrial fibrillation (AF) after cardiac surgery. The aim of this study was to explore this potential association.

METHODS

Patients who underwent coronary artery bypass grafting and/or valvular surgery during 2016–2020 were included in an observational single-centre study. Data collected from the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry and a local CPB database were merged. Associations between individual CPB variables (CPB and aortic clamp times, arterial and central venous pressure, mixed venous oxygen saturation, blood flow index, bladder temperature and haematocrit) and new-onset AF were analysed using multivariable logistic regression models adjusted for patient characteristics, comorbidities and surgical procedure.

RESULTS

Out of 1999 patients, 758 (37.9%) developed new-onset AF. Patients with new-onset postoperative AF were older, had a higher incidence of previous stroke, worse renal function and higher EuroSCORE II and CHA2DS2-VASc scores and more often underwent valve surgery. Longer CPB time [adjusted odds ratio 1.05 per 10 min (95% confidence interval 1.01–1.08); P = 0.008] and higher flow index [adjusted odds ratio 1.21 per 0.2 l/m2 (95% confidence interval 1.02–1.42); P = 0.026] were associated with an increased risk for new-onset AF, while the other variables were not. A sensitivity analysis only including patients with isolated coronary artery bypass grafting supported the primary analyses.

CONCLUSIONS

CPB management following current guideline recommendations appears to have minor or no influence on the risk of developing new-onset AF after cardiac surgery.
Group sparse optimization for inpainting of random fields on the sphere
Authors: Li Chao , Chen Xiaojun
Published: September 2023

We propose a group sparse optimization model for inpainting of a square-integrable isotropic random field on the unit sphere, where the field is represented by spherical harmonics with random complex coefficients. In the proposed optimization model, the variable is an infinite-dimensional complex vector and the objective function is a real-valued function defined by a hybrid of the $\ell _2$ norm and non-Lipschitz $\ell _p (0<p<1)$ norm that preserves rotational invariance property and group structure of the random complex coefficients. We show that the infinite-dimensional optimization problem is equivalent to a convexly-constrained finite-dimensional optimization problem. Moreover, we propose a smoothing penalty algorithm to solve the finite-dimensional problem via unconstrained optimization problems. We provide an approximation error bound of the inpainted random field defined by a scaled Karush–Kuhn–Tucker (KKT) point of the constrained optimization problem in the square-integrable space on the sphere with probability measure. Finally, we conduct numerical experiments on band-limited random fields on the sphere and images from Cosmic Microwave Background (CMB) data to show the promising performance of the smoothing penalty algorithm for inpainting of random fields on the sphere.
Post-report antibiotic initiation following community non-sterile-site microbiology results: an opportunity for labs to lead stewardship?
Authors: Bloomfield Max , Todd Sue , van der Werff Koen , Blackmore Tim , Balm Michelle
Published: September 2023

Objectives

Positive culture results from non-sterile sites (NSSs) are poorly predictive of clinical infection. Despite this, these results are often interpreted as an indication for antibiotics, even in patients with limited signs of infection. We sought to quantify the influence of NSS culture results on post-report antibiotic initiation (PRAI) in patients who had not been started on antibiotics pre-report.

Methods

All community wound/skin swab and sputum cultures were matched to antibiotic dispensing records from February 2017 to July 2022. Prescribing behaviour was assessed pre- and post-report. Sampling without treatment pre-report was termed ‘test-and-wait’ (TaW). Following TaW, PRAI was identified if antibiotics were started within 5 days post-report.

Results

There were 65 480 wound/skin swabs and 8126 sputum samples, with TaW occurring in 21 740 (35.1%) and 4185 (54.4%), respectively. Following a TaW approach PRAI occurred in 43.3% when an organism was reported, versus 10.8% (P < 0.01) for a ‘no growth’ report for wound/skin swabs. For the same comparison with sputum, PRAI occurred in 47.9% versus 10.8% (P < 0.01). On multivariate analysis reporting an organism remained strongly associated with PRAI.

Conclusions

Reporting an organism in those not already on antibiotics was strongly associated with PRAI. We hypothesize that for many patients TaW suggests limited evidence of infection (i.e. insufficient to justify antibiotic treatment at time of sampling), meaning positive NSS results may be driving a considerable volume of potentially unnecessary antibiotic use. Further study on this topic is required, but strategies to reduce PRAI may offer laboratories an opportunity to meaningfully impact antimicrobial stewardship efforts.
Scale of analysis drives the observed ratio of spatial to non-spatial variance in microbial water quality: insights from two decades of citizen science data
Authors: Weller Daniel L , Love Tanzy M T , Weller Donald E , Murphy Claire M , Strawn Laura K
Published: September 2023

Aims

While fecal indicator bacteria (FIB) testing is used to monitor surface water for potential health hazards, observed variation in FIB levels may depend on the scale of analysis (SOA). Two decades of citizen science data, coupled with random effects models, were used to quantify the variance in FIB levels attributable to spatial versus temporal factors.

Methods and results

Separately, Bayesian models were used to quantify the ratio of spatial to non-spatial variance in FIB levels and identify associations between environmental factors and FIB levels. Separate analyses were performed for three SOA: waterway, watershed, and statewide. As SOA increased (from waterway to watershed to statewide models), variance attributable to spatial sources generally increased and variance attributable to temporal sources generally decreased. While relationships between FIB levels and environmental factors, such as flow conditions (base versus stormflow), were constant across SOA, the effect of land cover was highly dependent on SOA and consistently smaller than the effect of stormwater infrastructure (e.g. outfalls).

Conclusions

This study demonstrates the importance of SOA when developing water quality monitoring programs or designing future studies to inform water management.
G protein-coupled bile acid receptor 1 reduced hepatic immune response and inhibited NFκB, PI3K/AKT, and PKC/P38 MAPK signaling pathway in hybrid grouper
Authors: Xu Jia , Cao Junming , Tan Beiping , Xie Shiwei
Published: September 2023

The mammalian G protein-coupled bile acid receptor 1 (TGR5) is involved in the inflammatory response. However, the functions of TGR5 in the immune response of fish remain unclear. In this study, the full-length sequence of tgr5 from hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) was cloned, and the function of TGR5 in the immune response was explored. The results showed that the ORF of tgr5 gene in hybrid grouper was 1029 bp and encoded 342 amino acids. Activation of TGR5 by INT-777 significantly decreased the activities and mRNA expression of TNFα and IL1β, whereas inhibition of TGR5 by SBI-115 showed the opposite effect. SBI-115 treatment significantly increased the expression of phosphorylated inhibitor κB α (p-IKBα) protein. After the INT-777 treatment, the concentration of protein kinase C (PKC) and expression of the p38 mitogen-activated protein kinases (p38a), p38b and p38c, were significantly decreased in vivo. INT-777 agonist significantly decreased the expression of phosphorylated phosphoinositide 3-kinase (p-PI3K) protein and the ratio of phosphorylated and nonphosphorylated serine/threonine-protein kinase (p-AKT/AKT). In conclusion, activation of hepatic TGR5 inhibited the PKC/P38 MAPK, PI3K/AKT, NFκB signaling pathway and improved hepatic immune responses of hybrid grouper in vivo and in vitro.
Patient Notification About Breast Arterial Calcification on Mammography: Empowering Women With Information About Cardiovascular Risk
Authors: Vincoff Nina S , Ramos Aderonke A , Duran-Pilarte Elizabeth , Derobertis Alicia , Daniel Woodlynn , Bajwa Bakhtawar N , Petrone Eric , Kline Myriam , Pavel Donatella M , Rosen Stacey E
Published: September 2023

Objective

To assess the impact of informing women about the presence of breast arterial calcification (BAC) on mammography by determining whether those notified about the presence of BAC would seek cardiovascular evaluation.

Methods

This IRB-approved prospective study included 494 patients who underwent screening mammography between June 8, 2021, and April 22, 2022. Mammograms were reviewed by a radiologist, and patients were notified via e-mail about the presence or absence of BAC. Patients with BAC were advised to discuss the results with their physicians and were surveyed 3 months later. Frequencies and proportions were calculated for study participation, presence of BAC, survey participation, health actions, and perceptions. Confidence intervals were calculated for proportions of health actions and perceptions.

Results

Of 494 study participants, 68/494 (13.8%; 95% CI: 10.9%–17.1%) had BAC detected on mammography and 42/68 (61.8%; 95% CI: 61.1%–62.1%) with BAC completed the follow-up survey at 3 months. Of these 42 survey respondents, 24/42 (57.1%; 95% CI: 41.1%–72.3%) reported discussing results with their primary care physician (PCP) or a cardiologist. In addition, 34/42 (81.0%; 95% CI: 65.9%–91.4%) reported finding it helpful to receive information about BAC and 32/42 (76.2%; 95% CI: 60.6%–88.0%) believed all women should be informed about BAC after mammography.

Conclusion

After notification about the presence of BAC on screening mammography, the majority (57.1%) of survey respondents reported discussing the results with a PCP or cardiologist. These results suggest that providing mammography patients with information about BAC may promote preventive cardiovascular health.
Holdout predictive checks for Bayesian model criticism
Authors: Moran Gemma E , Blei David M , Ranganath Rajesh
Published: September 2023

Bayesian modelling helps applied researchers to articulate assumptions about their data and develop models tailored for specific applications. Thanks to good methods for approximate posterior inference, researchers can now easily build, use, and revise complicated Bayesian models for large and rich data. These capabilities, however, bring into focus the problem of model criticism. Researchers need tools to diagnose the fitness of their models, to understand where they fall short, and to guide their revision. In this paper, we develop a new method for Bayesian model criticism, the holdout predictive check (HPC). Holdout predictive check are built on posterior predictive check (PPC), a seminal method that checks a model by assessing the posterior predictive distribution on the observed data. However, PPC use the data twice—both to calculate the posterior predictive and to evaluate it—which can lead to uncalibrated p-values. Holdout predictive check, in contrast, compare the posterior predictive distribution to a draw from the population distribution, a heldout dataset. This method blends Bayesian modelling with frequentist assessment. Unlike the PPC, we prove that the HPC is properly calibrated. Empirically, we study HPC on classical regression, a hierarchical model of text data, and factor analysis.
Wordplay in 1 Corinthians
Authors: Ciampa Roy E , Rosner Brian S
Published: September 2023

This essay provides the first attempt at a complete inventory and assessment of the use of wordplay in 1 Corinthians. It is organized by attending to the various linguistic features that are exploited to create wordplays. These include the use of different lexemes based on the same root (i.e., sharing etymology; compound words) used in close proximity; the use of the same lexeme but with different meanings in different genders, used in close proximity to exploit the euphony; the use of the same word/lexeme with different meanings in close proximity; the use of the same word with the same meaning twice in close proximity but in a context that plays on an inversion or twist while also exploiting the soundplay; and the use of different lexemes with similar sounds employed for the sake of the surprising rhetorical effect of connecting the two words. It also analyses the kinds of wordplay opportunities that each linguistic feature tends to provide or create. Additionally, it discusses the challenges that different wordplays create for translation (with a focus on translation into English). In the process, the ubiquity and significance of wordplays in 1 Corinthians is demonstrated.
Power purchase agreements and sustainable energy development: an approximation to the Cuban legal system
Authors: Luis Cordova José Grabiel , Jiménez Zulueta Lilianys , Byttebier Koen
Published: September 2023

Humanity since its origins as a species has depended on energy for its existence and development. The various energy crises that have occurred have had major negative impacts on both the economic and social spheres. The current worrying world energy situation, characterized by a constant increase in demand, polluting emissions and rising prices of energy, as well as an inevitable depletion of fossil fuels, has in recent years generated a general awareness of the need to develop sustainable energy solutions. Currently, the high dependence on foreign suppliers for energy imports has put the accessibility and affordability of energy at risk, and States have had to develop numerous initiatives to protect consumers from volatile energy prices. In this framework, widespread energy production through renewable energy sources and the use of Power Purchase Agreements (PPAs) emerge as tools to achieve energy security and mitigate energy vulnerability and poverty. This research aims to contribute to this effort by making an approximation to the Cuban legal and institutional framework of PPAs. Cuba, in line with the current global energy context, is in search of energy sovereignty based on renewable energy sources. Throughout this article, it is intended to substantiate the need to regulate PPAs in the pursuit of sustainable energy development solutions. With the enactment of Decree Law 345 of 2019 for the promotion of renewable energy sources and efficient energy use and its complementary rules, the first regulatory foundations for PPAs have been laid. While the Cuban legal energy system has been making substantial progress regarding PPAs, it must still strive to be further perfected.
Hormonal regulation of plant primary metabolism under drought
Authors: Yoshida Takuya , Fernie Alisdair R
Published: September 2023

Phytohormones are essential signalling molecules globally regulating many processes of plants, including their growth, development, and stress responses. The promotion of growth and the enhancement of stress resistance have to be balanced, especially under adverse conditions such as drought stress, because of limited resources. Plants cope with drought stress via various strategies, including the transcriptional regulation of stress-responsive genes and the adjustment of metabolism, and phytohormones play roles in these processes. Although abscisic acid (ABA) is an important signal under drought, less attention has been paid to other phytohormones. In this review, we summarize progress in the understanding of phytohormone-regulated primary metabolism under water-limited conditions, especially in Arabidopsis thaliana, and highlight recent findings concerning the amino acids associated with ABA metabolism and signalling. We also discuss how phytohormones function antagonistically and synergistically in order to balance growth and stress responses.