bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose Monitoring and Sensing
Authors: Pickup John , Oliver Nick 
Published: January 2022

Abstract
Glucose monitoring is critical to enable people with diabetes to self-manage effectively, especially those with insulin-treated diabetes. Self-monitoring of capillary blood glucose (SMBG) has been available to people with diabetes for four decades and is now being supplemented and, for some, superseded by continuous glucose monitoring (CGM) provided by subcutaneously implanted sensors. Information such as estimated glucose concentrations, rate of change, alerts for impending glucose extremes and historical patterns can enable more appropriate carbohydrate intake, physical activity, insulin administration, and lifestyle decisions in real-time. Improvements in overall glycaemic control, as measured by HbA1c, time-in-range for glucose readings, hypoglycaemia exposure, and hypoglycaemic events, as well as quality of life, have all been reported with CGM. Flash glucose monitoring (FGM) with retrospective review of previously recorded continuous glucose readings from a subcutaneous glucose sensor is likely to be a replacement for SMBG. Sensor-augmented insulin pump therapy uses CGM data for feedback control of insulin delivery, and pumps with automatic low glucose-activated suspend of the basal insulin infusion are already in widespread clinical use and effective at reducing hypoglycaemia in type 1 diabetes. Hybrid closed-loop systems employing CGM are entering practice and fully closed-loop systems are under development.
Strategies for the Management of Type 2 Diabetes
Authors: Winocour Peter , Zac-Varghese Sagen 
Published: January 2022

Abstract
The approach to the management of hyperglycaemia in type 2 diabetes has become increasingly complex with a widening armamentarium of available antihyperglycaemic agents. It is well recognized that several agents have additional benefits (outside of glucose control), for example, on weight management and on cardiovascular and renal outcomes. Recent cardiovascular outcome trial data has had an impact on treatment algorithms. This chapter looks at strategies for deploying the various agents. The initiation of therapy, intensification of therapy, and combination of agents is discussed. The choice of agent in particular circumstances, in cardiovascular disease, renal disease, and hepatic impairment is discussed. Successful management requires a patient-centred approach with careful consideration of the risks and benefits of the treatment options.
Psychological and Behavioural Aspects of Type 2 Diabetes Management
Authors: Skinner Timothy C. , Speight Jane 
Published: January 2022

Abstract
Type 2 diabetes is a complex condition requiring attention to blood glucose, blood pressure, cholesterol, and emotional well-being. The overall objective of diabetes self-management is to reduce these risk factors, thereby preventing, delaying, or minimizing risk of long-term complications. Typical strategies include informed dietary choices and physical activity, medication taking and monitoring glucose levels; and, for many, this will also include the challenge of sustaining some weight loss. Substantial advances in medical technologies and treatments in the past 20 years have not been matched with comparable improvements in biomedical outcomes. This chapter highlights five common facets or ‘SHADEs’ of diabetes distress: Scared, Helpless, Alone, Deprived, and Exhausted. As the role of health professionals is not to manage diabetes but rather support people to self-manage their own diabetes, this acronym can be used in clinical practice to identify constructive and creative ways to motivate and sustain effective self-management.
Regenerative Medicine for Diabetes
Authors: White Michael G. , Ellis Cara E. , Kieffer Timothy J. 
Published: January 2022

Abstract
Insulin-dependent diabetes affects millions of people worldwide and results in significant burdens to both patients and healthcare systems. Islet transplantation provides superior glycaemic control compared to the standard therapy of injectable insulin, with decreased risk of hypoglycaemia. However, cadaveric donor islets will never be a sufficient supply of insulin-producing cells to treat all patients, and the need for chronic immunosuppression to protect the grafts limits the pool of candidates for the procedure. Years of research unravelling the complex processes and signalling pathways that lead to the differentiation and maturation of beta cells during development has facilitated the advancement of multiple diverse strategies towards creating potentially unlimited numbers of insulin-producing cells to treat insulin-dependent diabetes. In this chapter, we review some of the recent progress towards generating beta cells from pluripotent stem cells and inducing expansion of endogenous beta cells.
Hyperglycaemic Emergencies
Authors: Dhatariya Ketan 
Published: January 2022

Abstract
Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic syndrome (HHS) are the most commonly occurring metabolic medical emergencies. They are seldom the first presentation of diabetes, but most frequently occur due to infection, or non-concordance with prescribed medications. The diagnosis of DKA should only be made if all three components (the ‘D’, the ‘K’, and the ‘A’) are present—with a history of diabetes or a glucose concentration of ≥11.1 mmol/L; a ketone concentration of ≥3.0 mmol/L; and a pH &lt;7.3 and/or a serum bicarbonate of &lt;15.0 mmol/L. HHS has no formal diagnostic criteria but should have a glucose of &gt;30.0 mmol/L, a calculated serum osmolality of &gt;320 mOsmol/Kg and the absence of ketones. The management of DKA and HHS are different, and national guidelines exist for both. Both conditions require the administration of intravenous fluid with 0.9% sodium chloride solution to treat the dehydration frequently seen. In DKA, aggressive fluid replacement should accompany a weight based, fixed rate intravenous insulin infusion given at 0.1 units/kg/hour, as well as potassium replacement after the first litre of fluid has been administered. In HHS, fluid and electrolyte replacement are the mainstay of initial treatment, with insulin only being added at 0.05 units/kg/hour once the glucose concentration and osmolality has stopped falling. For both conditions, the early involvement of the specialist diabetes inpatient team is strongly recommended to help guide treatment and also to provide ongoing care and support once the DKA or HHS has resolved and the patient is discharged.
Diabetes in Pregnancy
Authors: Murphy Helen R. , Yamamoto Jennifer M. 
Published: January 2022

Abstract
Although there have been many advances in the treatment of diabetes, the goal of the St. Vincent Declaration (1989) that the outcome of diabetic pregnancy approximates that of non-diabetic pregnancy has still not been realized. Women with diabetes still have an increased risk of pregnancy-related complications including preterm delivery, large-for-gestational-age, neonatal hypoglycaemia, congenital anomaly, stillbirth, and neonatal death. The landscape of diabetes in pregnancy has changed dramatically with one in six pregnancies affected by maternal hyperglycaemia. Approximately half of all women with pre-gestational diabetes in pregnancy now have pre-gestational type 2 diabetes (T2D). This represents a 90% increase in the proportion of pregnancies complicated by T2D over 15 years. Likewise, recent data suggest a 44% increase in the number of pregnancies complicated by type 1 diabetes (T1D). While there remains much room for improvement, pregnancy outcomes for most women with diabetes are good. This likely reflects improvements such as obstetric surveillance, tighter glycaemic targets, improved diabetes technologies, and specialized interdisciplinary teams. There is also evidence of recent improvements, with a 2.5-fold reduction in stillbirths in a large contemporary UK cohort of women with pre-gestational diabetes in pregnancy compared to 15 years earlier. The goal now is to further improve pregnancy outcomes in women with diabetes by optimizing pre-pregnancy care, glycaemic control, and obstetric and diabetes-related surveillance using targeted education, technology, specialized teams, and by empowering women with diabetes.
Diabetic Dyslipidaemia
Authors: Vergès Bruno 
Published: January 2022

Abstract
Diabetic dyslipidaemia plays an important role in the increased cardiovascular risk of type 2 diabetes. It encompasses not only quantitative lipoprotein abnormalities, but also qualitative and kinetic abnormalities that, together, result in a shift toward a more atherogenic lipid profile. The principal quantitative lipoprotein abnormalities are increased triglyceride levels and decreased high-density lipoprotein (HDL) cholesterol levels. Qualitative lipoprotein abnormalities include increases in large, very low-density lipoprotein subfraction 1 (VLDL1) and small, dense low-density lipoproteins (LDLs), increased triglyceride content of LDLs and HDLs, glycation of apolipoproteins, and increased susceptibility of LDLs to oxidation. Moreover, HDLs from diabetic patients are dysfunctional, having severely reduced antiatherogenic properties. Statin use is recommended in most patients with T2DM because of the cardiovascular benefit demonstrated in many trials. Some post-hoc analyses of trials with fenofibrate suggest a potential CVD reduction in diabetic patients with triglycerides ≥2.6 mmol/L and low HDL cholesterol.
Endocrine Evaluation
Authors: Kaufman Jean-Marc 
Published: January 2022

Abstract
Suspected hypogonadism is confirmed if serum testosterone (T) is consistently and unequivocally low, ascertained in fasting morning blood samples on at least two separate occasions. In situations with altered sex-hormone-binding globulin (SHBG) concentrations, serum-free T is more representative of gonadal status than total T. Serum gonadotropin concentrations differentiate primary hypogonadism of testicular origin with elevated gonadotropins from secondary hypogonadism due to hypothalamic-pituitary malfunction with low or inappropriately normal levels. Additional investigations may include chromosome karyotyping in primary hypogonadism, and serum prolactin, pituitary hormonal testing, imaging, and genetic mutation testing in secondary hypogonadism. Serum levels of T precursors and metabolites, insulin-like peptide-3, inhibin B, or anti-Müllerian hormone do not significantly contribute to the work-up of adult men suspected of hypogonadism. In men with subfertility, high serum FSH indicates deficient spermatogenesis; low inhibin B is equally informative without substantially adding information above that from high FSH.
Diagnostic Semen Analysis
Authors: Kirkman-Brown Jackson C. , Conner Sarah J. 
Published: January 2022

Abstract
Semen analysis is a cornerstone of assessing male reproductive function, but to be correctly interpreted, one must understand that: an individual’s sperm production itself may vary widely over a number of months; how the WHO ‘normal’ laboratory reference ranges were derived; the accuracy of the reported laboratory assessments and potential causes for error. Results such as a total absence of sperm (azoospermia) may vary over time and between laboratories, depending upon the quality of laboratory assessment. It is therefore key to work with laboratories accredited specifically for semen analysis. Discussion provided within this chapter should assist with deciphering correct clinical interpretation of results.
Induction of Spermatogenesis by Gonadotrophin Treatment
Authors: Zitzmann Michael 
Published: January 2022

Abstract
Male hypogonadism (inherited or acquired) is often associated with impaired fertility. In patients with hypogonadotropic hypogonadism due to pituitary damage (secondary hypogonadism, lacking secretion of gonadotropins), that is luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or tertiary hypogonadism due to damage of the hypothalamic area (lacking gonadotropin-releasing hormone [GnRH]), treatment with GnRH or LH/FSH can induce, maintain, or augment spermatogenesis. Recombinant FSH and human chorionic gonadotropin (ß-hCG, substituting activity of LH) are the most commonly used preparations for gonadotrophin replacement. Successful induction of spermatogenesis is more likely in men with pituitary disorders than in those lacking hypothalamic GnRH secretion (tertiary disorders) such as Kallmann syndrome.
Shakespeare: Songs & Sonnets
Authors: Duffin Ross W 
Published: January 2022

ABSTRACT
Considering the fame of the poet and the beauty of the poetry, it is intriguing and somewhat baffling that there are no musical settings of Shakespeare’s sonnets from his lifetime, whether from lack of preservation or a disinclination on the part of composers to set them. This was first wondered at by Charles Burney in 1789, but is essentially explained away today as ‘sonnets are pure poetry’. This article explores possible reasons for the avoidance of sonnet settings in the early song repertory, including the language, versification, structure, and subject matter. The few surviving period sonnet settings are analysed, alongside a version of Sonnet 116 by Henry Lawes, the sole surviving Shakespeare sonnet setting from the seventeenth century. Using criteria from that study, a conjectural musical setting of a Shakespeare sonnet is proposed, based on an existing song by John Dowland.
The three hundred project: galaxy cluster mergers and their impact on the stellar component of brightest cluster galaxies
Authors: Contreras-Santos Ana , Knebe Alexander , Pearce Frazer , Haggar Roan , Gray Meghan , Cui Weiguang , Yepes Gustavo , De Petris Marco , De Luca Federico , Power Chris , Mostoghiu Robert , Nuza Sebastián E , Hoeft Matthias 
Published: January 2022

ABSTRACT
Using the data set of the three hundred project, i.e. a suite of 324 hydrodynamical resimulations of cluster-sized haloes, we study galaxy cluster mergers and their effect on colour and luminosity changes of their brightest cluster galaxies (BCG). We track the main progenitor of each halo at z = 0 and search for merger situations based on its mass accretion history, defining mergers as very rapid increases in the halo mass. Based upon the evolution of the dynamical state of the cluster we define a pre- and post-merger phase. We create a list of all these events and statistically study their mass ratio and time-scales, with the former verifying that all instances are in fact major mergers. By comparing to a control sample of clusters without mergers, we study the effect mergers have on the stellar component of the BCG. Analysing the mass, age, and metallicity of the BCG stellar particles, we find that the stellar content of BCGs grows significantly during mergers and, even though the main growth mechanism is the accretion of older stars, there is even a burst in star formation induced by the merger. In our simulations, BCGs in mergers form in median around 70 per cent more stars than those normally growing, although this depends on the radius considered for defining the BCG. Regarding observable properties, we see an increase in SDSS-u luminosity of 20 per cent during mergers, accompanied by a slightly slower increase of the galaxy g − r colour as compared to the control sample.
YOUNG Star detrending for Transiting Exoplanet Recovery (YOUNGSTER) – II. Using self-organizing maps to explore young star variability in sectors 1–13 of TESS data
Authors: Battley Matthew P , Armstrong David J , Pollacco Don 
Published: January 2022

ABSTRACT
Young exoplanets and their corresponding host stars are fascinating laboratories for constraining the time-scale of planetary evolution and planet–star interactions. However, because young stars are typically much more active than the older population, in order to discover more young exoplanets, greater knowledge of the wide array of young star variability is needed. Here Kohonen self-organizing maps (SOMs) are used to explore young star variability present in the first year of observations from the Transiting Exoplanet Survey Satellite (TESS), with such knowledge valuable to perform targeted detrending of young stars in the future. This technique was found to be particularly effective at separating the signals of young eclipsing binaries and potential transiting objects from stellar variability, a list of which are provided in this paper. The effect of pre-training the SOMs on known variability classes was tested, but found to be challenging without a significant training set from TESS. SOMs were also found to provide an intuitive and informative overview of leftover systematics in the TESS data, providing an important new way to characterize troublesome systematics in photometric data sets. This paper represents the first stage of the wider YOUNGSTER program, which will use a machine-learning-based approach to classification and targeted detrending of young stars in order to improve the recovery of smaller young exoplanets.
Moving nickel along the hydrogenase–urease maturation pathway
Authors: Tsang Ka Lung , Wong Kam-Bo 
Published: January 2022

Abstract
Hydrogenases and ureases play vital metabolic functions in all three domains of life. However, nickel ions are cytotoxic because they can inactivate enzymes that require less competitive ions (e.g. Mg2+) in the Irving–Williams series to function. Life has evolved elegant mechanisms to solve the problem of delivering the toxic metal to the active site of nickel-containing enzymes inside the cells. Here, we review our current understanding of nickel trafficking along the hydrogenase and urease maturation pathways. Metallochaperones and accessory proteins (SlyD, HypA, HypB, UreD, UreE, UreF, and UreG) form specific protein complexes to allow the transfer of nickel from one protein to another without releasing the toxic metal into the cytoplasm. The role of SlyD is not fully understood, but it can interact with and transfer its nickel to HypB. In the hydrogenase maturation pathway, nickel is transferred from HypB to HypA, which can then deliver its nickel to the hydrogenase large subunit precursor. In Helicobacter pylori, the urease maturation pathway receives its nickel from HypA of the hydrogenase maturation pathway via the formation of a HypA/UreE2 complex. Guanosine triphosphate (GTP) binding promotes the formation of a UreE2G2 complex, where UreG receives a nickel from UreE. In the final step of the urease maturation, nickel/GTP-bound UreG forms an activation complex with UreF, UreD, and apo-urease. Upon GTP hydrolysis, nickel is released from UreG to the urease. Finally, some common themes learned from the hydrogenase–urease maturation pathway are discussed.
The first crystal structures of hybrid and parallel four-tetrad intramolecular G-quadruplexes
Authors: Beseiso Dana , Chen Erin V , McCarthy Sawyer E , Martin Kailey N , Gallagher Elizabeth P , Miao Joanne , Yatsunyk Liliya A 
Published: January 2022

Abstract
G-quadruplexes (GQs) are non-canonical DNA structures composed of stacks of stabilized G-tetrads. GQs play an important role in a variety of biological processes and may form at telomeres and oncogene promoters among other genomic locations. Here, we investigate nine variants of telomeric DNA from Tetrahymena thermophila with the repeat (TTGGGG)n. Biophysical data indicate that the sequences fold into stable four-tetrad GQs which adopt multiple conformations according to native PAGE. Excitingly, we solved the crystal structure of two variants, TET25 and TET26. The two variants differ by the presence of a 3′-T yet adopt different GQ conformations. TET25 forms a hybrid [3 + 1] GQ and exhibits a rare 5′-top snapback feature. Consequently, TET25 contains four loops: three lateral (TT, TT, and GTT) and one propeller (TT). TET26 folds into a parallel GQ with three TT propeller loops. To the best of our knowledge, TET25 and TET26 are the first reported hybrid and parallel four-tetrad unimolecular GQ structures. The results presented here expand the repertoire of available GQ structures and provide insight into the intricacy and plasticity of the 3D architecture adopted by telomeric repeats from T. thermophila and GQs in general.
Surgical and oncological score to estimate the survival benefit of resection and chemoradiotherapy in elderly (≥70 years) glioblastoma patients: A preliminary analysis
Authors: Zorman Mark J , Webb Philip , Nixon Mickaela , Sravanam Sanskrithi , Honeyman Susan , Nandhabalan Meera , Apostolopoulos Vasileios , Stacey Richard , Hobbs Claire , Plaha Puneet 
Published: January 2022

Abstract

Background
Elderly patients with glioblastoma are perceived to face a poor prognosis with perceptions surrounding older age and a relative lack of randomized data contributing. This study evaluated survival prognosticators in elderly glioblastoma patients to more accurately guide their treatment.

Methods
The records of 169 elderly (≥70 years) patients with a new diagnosis of glioblastoma who had undergone neurosurgical intervention were retrospectively examined for patient sex, age, performance status, comorbidities, MGMT promoter methylation, surgical intervention, and chemoradiation regime. The adjusted survival impact of these factors was determined using Cox proportional hazards model and used to devise a two-stage scoring system to estimate patient survival at the stage of surgical (Elderly Glioblastoma Surgical Score, EGSS) and oncological management (Elderly Glioblastoma Oncological Score, EGOS).

Results
The median overall survival (mOS) of the cohort was 28.8 weeks. Gross-total and subtotal resection were associated with improved survival compared to biopsy alone (respective mOS 65.3 and 28.1 vs 15.7 weeks, P &lt; .001). Hypofractionated radiotherapy (40Gy in 15 fractions) with Temozolomide was noninferior to the Stupp protocol, P = .72. Exploratory subgroup analysis revealed a significant benefit of Temozolomide-based approaches in MGMT-methylated patients as well as a trend towards improved survival in MGMT-unmethylated patients. Our EGSS and EGOS scores successfully estimated survival in this retrospective cohort with 65% and 73% accuracy.

Conclusions
Where appropriate and safe, elderly glioblastoma patients may benefit from surgical resection and combined chemoradiotherapy with Temozolomide. The proposed EGSS and EGOS scores take into account important prognostic factors to help guide which patients should receive such treatment.
Exposure to Low UV-B Dose Induces DNA Double-Strand Breaks Mediated Onset of Endoreduplication in Vigna radiata (L.) R. Wilczek Seedlings
Authors: De Sayanti , Jose Jismon , Pal Amita , Roy Choudhury Swarup , Roy Sujit 
Published: January 2022

Abstract
Multiple lines of evidence indicate that solar UV-B light acts as an important environmental signal in plants, regulating various cellular and metabolic activities, gene expression, growth and development. Here, we show that low levels of UV-B (4.0 kJ m−2) significantly influence plant response during early seedling development in the tropical legume crop Vigna radiata (L.) R. Wilczek. Exposure to low doses of UV-B showed relatively less growth inhibition yet remarkably enhanced lateral root formation in seedlings. Both low and high (8.0 kJ m−2) doses of UV-B treatment induced DNA double-strand breaks and activated the SOG1-related ATM-ATR-mediated DNA damage response pathway. These effects led to G2-M-phase arrest with a compromised expression of the key cell cycle regulators, including CDKB1;1, CDKB2;1 and CYCB1;1, respectively. However, along with these effects, imbibitional exposure of seeds to a low UV-B dose resulted in enhanced accumulation of FZR1/CCS52A, E2Fa and WEE1 kinase and prominent induction of endoreduplication in 7-day-old seedlings. Low dose of UV-B mediated phenotypical responses, while the onset of endoreduplication appeared to be regulated at least in part via UV-B induced reactive oxygen species accumulation. Transcriptome analyses further revealed a network of co-regulated genes associated with DNA repair, cell cycle regulation and oxidative stress response pathways that are activated upon exposure to low doses of UV-B.