bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carney’s Complex
Authors: Stratakis Constantine A. , Faucz Fabio R. 
Published: January 2022

Abstract
Carney complex (CNC) is a rare autosomal dominant syndrome that was first described in 1985 and is characterized by pigmented lesions of the skin and mucosa, cardiac, cutaneous, and other myxomas, and multiple endocrine tumours. The disease is mostly caused by inactivating mutations or large deletions of the PRKAR1A gene located at 17q22–24 coding for the regulatory subunit type I alpha of protein kinase A (PKA) gene but other causative genetic defects on chromosome 2p16 and perhaps elsewhere remain unknown. Most recently, components of the complex have been associated with defects of other PKA subunits, such as the catalytic subunits PRKACA (adrenal hyperplasia) and PRKACB (pigmented spots, myxomas, pituitary adenomas). The chapter reviews CNC, its clinical features, diagnosis, treatment, and molecular aetiology.
Menstrual Cycle and Ovulation
Authors: Bozdag Gurkan , Ata Baris , Türkgeldi Engin 
Published: January 2022

Abstract
Understanding the physiology of follicular development is important in order to extrapolate the preclinical data to the clinical side. In this context, there has been an increasing effort to figure out the autocrine/paracrine signalling and microenvironment that will determine the fate of a follicle. The processes of atresia or further development to later stages reaching to a dominant follicle appear to be regulated by highly complicated system that consists oocyte and granulosa cell derived factors, peptides, cytokines, and sex steroids. Additionally, recent research on the menstrual cycle that yields the presence of more than one wave of follicular cohort growing within a single period will undoubtedly implicate our perception on reproductive function, hormonal contraception, and ovarian stimulation during an assisted reproduction treatment. This chapter reviews the current knowledge that reflects the timetable of a follicle throughout the early ages to the formation of dominant follicle and corresponding endometrial changes.
Hyperprolactinaemia
Authors: Davis Julian , Święcicka Agnieszka 
Published: January 2022

Abstract
Hyperprolactinaemia is a common clinical problem with important effects on reproductive function. The condition is often drug-induced but potential pituitary disease, including micro- and macroprolactinoma and non-tumoural hyperprolactinaemia, requires evaluation. Treatment is usually with dopamine agonist drugs such as cabergoline, which suppress hyperprolactinaemia in most patients, and allow restoration of regular ovulation in women. Even large pituitary tumours usually display marked shrinkage with dopamine agonist treatment, hence pituitary surgery is rarely necessary. Women who become pregnant with dopamine agonists usually discontinue the drug during pregnancy, but have a small risk of significant pituitary enlargement.
Premenstrual Syndrome
Authors: Lavu Deepthi , Indusekhar Radha , O’Brien Shaughn 
Published: January 2022

Abstract
Millions of women and their families around the world are affected by premenstrual disorders. These conditions cause significant impairment for women, resulting in emotional, somatic, and/or behavioural symptoms in the luteal phase of the menstrual cycle. Following the recent International Society for Premenstrual Disorders (ISPMD) consensus, these disorders have been divided into core and variant premenstrual disorders. Diagnosis is complex as there are no objective tests. Use of a prospective symptom scoring chart, by women, to record their daily symptoms is recommended to support a definitive diagnosis in addition to a multidisciplinary team approach for management of women with premenstrual syndrome (PMS). Treatments are broadly divided into two categories, based on ovulation suppression and neuroendocrine manipulation. These include lifestyle modifications, cognitive behaviour therapy, combined oral contraception, selective serotonin reuptake inhibitors, oestradiol, and progesterone, gonadotrophin-releasing hormone analogues and surgery (bilateral salpingo-ophorectomy and hysterectomy) as a last resort.
Exogenous Factors and Female Reproductive Health
Authors: Gambineri Alessandra , Ibarra-Gasparini Daniela 
Published: January 2022

Abstract
Female infertility affects 8–15% of reproductive-aged couples worldwide and ovulatory disorders account of more than a quarter of cases. It is defined as the failure to establish a clinical pregnancy after 12 months of regular and unprotected sexual intercourse in women younger than 35 and after six months in women over the age of 35. The ovaries and the uterus are under the control of many hormones such as LH, FSH, thyroid hormones, GH, prolactin, glucocorticoids, and sex steroids. Thus, an excess or defect of these hormones may account for female infertility. This chapter explains in detail the mechanisms by which each hormone regulates folliculogenesis, uterus decidualization, and embryo implantation in order to understand the complex regulation of female reproduction and of its alteration.
Tall Stature
Authors: Sävendahl Lars , Benyi Emelie 
Published: January 2022

Abstract
Tall stature is usually constitutional depending on the height of the father and mother. In some cases, there is an underlying condition affecting the complex regulation of growth which causes tall stature. For some individuals, extreme tall stature is associated with psychosocial problems and therapies aiming to reduce further growth have been available for decades, but some have been associated with undesired serious side effects. This chapter gives an overview of the aetiology behind and possible consequences of extreme tallness. The assessment of a tall child as well as treatment methods to reduce growth are summarized and ethical considerations regarding treatment are also discussed.
Disorders of Sex Development (DSD) in the Newborn
Authors: Ahmed S. Faisal , Ali Salma R. 
Published: January 2022

Abstract
The newborn infant with a suspected disorder of sex development (DSD) presents a challenging scenario. It is paramount that any such chid is assessed by an expert with adequate knowledge about the range of variation in the physical appearance of genitalia, the underlying pathophysiology of disorders of sex development and the strengths and weaknesses of the tests that can be performed in early infancy. By working within a multidisciplinary team, the DSD expert can ensure that the parents’ needs for information are comprehensively addressed and that appropriate investigations are performed in a timely fashion. In the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration so that any evidence for future changes in practice have a stronger foundation than that which is currently available.
The Endocrine Response to Stress
Authors: Henley David , Upton Thomas , Lightman Stafford L. 
Published: January 2022

Abstract
Reaction to stress is characterized by a series of interlinked, dynamic, and organized responses that function to restore homeostasis. Rapid activation of the sympathoadrenomedullary and hypothalamic–pituitary–adrenal (HPA) axes occurs following acute stress exposure in order to appropriately respond to, adapt, or escape the threat. The dynamic, pulsatile nature of the HPA axis is crucial to the function of glucocorticoids which modulate many of the complex neurocognitive and physiological changes that occur in acute and chronic stress states. Maladaptive long-term activation of the stress response is associated with numerous pathological states including mood and sleep disorders, obesity, and metabolic syndrome. The altered stress dynamics that occur in critical illness remain poorly understood.
Hormones and the Kidney
Authors: Nataatmadja Melissa , Cho Yeoungjee , Johnson David W. 
Published: January 2022

Abstract
Chronic kidney disease (CKD) is a growing global health problem and affects approximately 10–15% of the world’s population. The interactions between kidney disease and endocrine systems are complex, and endocrine abnormalities are common in patients with CKD. In particular, abnormalities in the renin–angiotensin–aldosterone system, parathyroid function, and erythropoietin production and responsiveness are common. In addition, thyroid disease, sexual dysfunction and abnormalities in prolactin, growth hormone, and insulin-like growth factor-1 are often seen. Here in this chapter, we outline common endocrine abnormalities seen in patients with CKD and their pathophysiology, and discuss important aspects of management of these conditions including screening and treatment.
Endocrine Complications of Biological Cancer Therapies
Authors: Moran Carla 
Published: January 2022

Abstract
In recent years, modulation of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways has resulted in significant improvements in cancer outcomes. Immune-related adverse events (IrAEs), including endocrinopathies, are common toxicities associated with use of these immune checkpoint inhibitors, with agents affecting the CTLA-4 pathway typically causing hypophysitis, and those affecting the PD-1 pathway most commonly causing thyroid dysfunction. Notably, due to non-specific and ill-defined symptoms, these endocrine-associated IrAEs can escape detection, such that surveillance for these side effects is warranted. Although these endocrinopathies may be irreversible, they are rarely life-threatening and there is emerging evidence that individuals experiencing such side effects have better cancer outcomes. With likely increasing use of these agents over the coming decade, endocrinologists can expect to diagnose and manage these side effects more frequently.
Endocrine Treatment of Breast Cancer
Authors: Sheri Amna , Morrison Laura 
Published: January 2022

Abstract
Endocrine manipulation is a well-recognized treatment modality for breast cancer and better understanding of the role of oestrogen in breast cancer pathogenesis has enabled advances in both early and metastatic breast cancer treatment. Two key pathways are used to reduce oestrogen levels—competition for the oestrogen receptor at the cell surface and by reducing peripheral androgen conversion. Adjuvant therapy with the oestrogen receptor antagonist tamoxifen shows improved disease-free and overall survival when given for ten years. Aromatase inhibitors have shown further benefits in the adjuvant setting either alone (in postmenopausal women) or in conjunction with ovarian suppression (in younger, premenopausal women). Endocrine therapy has had a significant impact on breast cancer treatment, but resistance develops in many patients. The mechanisms for this resistance are being investigated and there are a number of emerging treatment options that may help to overcome resistance although this is a complicated area of research.
Management of Obesity in Children and Young People
Authors: White Billy , Viner Russell M. 
Published: January 2022

Abstract
The management of obesity in childhood and adolescence poses challenges unique to this age group. Compared to adults, obesity-related comorbidities are relatively rare, yet risk factors are increasingly prevalent, frequently undetected, and poorly managed. The evidence base for weight loss interventions and management of comorbidities is limited, with short duration of follow-up only reported, and few randomized controlled trials. Bariatric surgery in adolescents results in the largest magnitude of weight loss, with outcomes similar to those seen in adults. Lifestyle intervention studies have relatively modest outcomes, with unknown long-term outcomes. Only one pharmaceutical agent (orlistat) is licenced in this age group, with generally poor outcomes.
Disorders of Carbohydrate Metabolism
Authors: Lachmann Robin H. 
Published: January 2022

Abstract
Sugar molecules play many roles in metabolism. Glucose is an essential source of energy in the body, but carbohydrates also have important structural and signalling functions as constituents of glycoproteins, glycolipids, and glycosaminoglycans. Disorders of carbohydrate metabolism, although caused be defects in individual enzymes, are best viewed as disorders of metabolic pathways. Their tissue pathology can be due to deficiency of a product of metabolism, but just as often it is due to accumulation of toxic molecules which cannot be metabolized. In this chapter, a number of monogenic diseases will be described which involve the monosaccharides glucose, galactose, and fructose, and their roles in intermediary metabolism. The many other inherited metabolic diseases which affect the formation of glycosylated macromolecules (the congenital disorders of glycosylation) or their breakdown (lysosomal storage disorders) will not be discussed.
Prevention of Type 2 Diabetes
Authors: Wareham Nicholas J. 
Published: January 2022

Abstract
The rising prevalence of type 2 diabetes and the costs of managing the condition in developed and developing countries alike has driven an increased focus on the potential to design and implement preventive interventions. Meta-analyses of randomized controlled trials of individual-level behavioural interventions aimed at changing dietary and physical activity behaviour, mediated in most but not all populations by weight loss, have unequivocally established that these interventions are efficacious under the ideal circumstances that exist in clinical trials. Achieving comparable effectiveness in real-world settings has been much more challenging and there are as yet few examples of effective, scalable, and inexpensive interventions. Even in settings where individual-level interventions are affordable, such approaches need to be complemented by whole population approaches to prevention that implicitly acknowledge that the public health problem of diabetes cannot be dealt with by clinical approaches alone and needs a balanced approach of individual and societal-level action.
“Closed Loop” Insulin Delivery
Authors: Hovorka Roman , Boughton Charlotte 
Published: January 2022

Abstract
Glycaemic control with insulin therapy is influenced by multiple factors, contributing to the notable variability in insulin requirements and making self-management of type 1 diabetes (T1D) challenging. As a result, the majority of people with T1D are unable to achieve their recommended therapeutic goals. Rapid progress has been made over the past decade with the development of a closed-loop insulin delivery system, also known as the ‘artificial pancreas’ which emulates the glucose-responsive functionality of the pancreatic beta cell. A control algorithm autonomously and continually increases and decreases subcutaneous insulin delivery based on real-time sensor glucose levels to achieve normoglycaemia while mitigating hyper- and hypoglycaemia. Randomized clinical studies in outpatient and home settings have demonstrated improved glycaemic outcomes, reduced risk of hypoglycaemia, and positive user attitudes. The Food and Drug Administration (FDA) approval of the first hybrid closed-loop system in 2017 marks a new era in the management of T1D using diabetes technology.
Macrovascular Disease in Type 2 Diabetes
Authors: Sattar Naveed 
Published: January 2022

Abstract
Disease of large blood vessels is a major cause of premature deaths in type 2 diabetes. On average the risk for macrovascular outcomes is approximately double in type 2 diabetes. Risk is heterogeneous, with relative risks higher in earlier onset type 2 diabetes, women, and certain ethnicities as well with longer duration of disease or the presence of microvascular complications. Over the last 2–3 decades, more aggressive risk factor management and earlier diagnosis have lowered myocardial infarctions and stroke risk in type 2 diabetes more so than in the general population in high income countries but CVD death rate reductions have been similar. The result is that other common cardiovascular complications including heart failure and peripheral arterial disease have grown in profile in type 2 diabetes. Going forwards, more aggressive management of younger patients, and increasing use of newer therapies with cardiovascular benefits, should help further lessen CVD risks in type 2 diabetes.
Hypertension in Diabetes Mellitus
Authors: Williams Bryan 
Published: January 2022

Abstract
High blood pressure (hypertension) is very common in people with diabetes. There is moreover an association between hypertension and diabetes that tracks through life, while the blood glucose concentration of young non-diabetic individuals has been shown to predict risk of future hypertension. Conversely, people with hypertension are twice as likely to develop type 2 diabetes over their lifetime. High blood pressure (hypertension) is arguably the most important preventable cause of premature microvascular and macrovascular disease and their associated morbidity and mortality in people with diabetes. This chapter will review key aspects of the epidemiology and pathophysiology of hypertension in people with diabetes, as well as recommended approaches to its clinical evaluation and treatment.
Diabetes Service Organization
Authors: Valabhji Jonathan 
Published: January 2022

Abstract
The World Health Organization has estimated that globally, 422 million adults were living with diabetes in 2014, compared to 108 million in 1980. Increasing prevalence of diabetes has required evolution of healthcare delivery systems. While the lens of the current article is the National Health Service in England, the challenges posed by increasing diabetes prevalence, and the implications to sustainability of healthcare systems, will be broadly applicable. Strategies to achieve sustainability may include: prevention of type 2 diabetes, including both interventions for those at high risk, as well as population level interventions; prevention of the complications of diabetes through better organization of care delivery; empowerment of individuals with diabetes to better self-manage their condition; establishment of digital technologies for healthcare provision; and achievement of integration of care delivery across the organizations that constitute healthcare systems. Models of diabetes service delivery that aim to achieve these policy goals are described.
Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibodies in Australia After the First Epidemic Wave in 2020: A National Survey
Authors: Vette Kaitlyn M , Machalek Dorothy A , Gidding Heather F , Nicholson Suellen , O’Sullivan Matthew V N , Carlin John B , Downes Marnie , Armstrong Lucy , Beard Frank H , Dwyer Dominic E , Gibb Robert , Gosbell Iain B , Hendry Alexandra J , Higgins Geoff , Hirani Rena , Hueston Linda , Irving David O , Quinn Helen E , Shilling Hannah , Smith David , Kaldor John M , Macartney Kristine 
Published: January 2022

Abstract

Background
As of mid-2021, Australia’s only nationwide coronavirus disease 2019 (COVID-19) epidemic occurred in the first 6 months of the pandemic. Subsequently, there has been limited transmission in most states and territories. Understanding community spread during the first wave was hampered by initial limitations on testing and surveillance. To characterize the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody seroprevalence generated during this time, we undertook Australia’s largest national SARS-CoV-2 serosurvey.

Methods
Between June 19 and August 6, 2020, residual specimens were sampled from people undergoing general pathology testing (all ages), women attending antenatal screening (20–39 years), and blood donors (20–69 years) based on the Australian population’s age and geographic distributions. Specimens were tested by Wantai total SARS-CoV-2-antibody assay. Seroprevalence estimates adjusted for test performance were produced. The SARS-CoV-2 antibody-positive specimens were characterized with microneutralization assays.

Results
Of 11 317 specimens (5132 general pathology; 2972 antenatal; 3213 blood-donors), 71 were positive for SARS-CoV-2-specific antibodies. Seroprevalence estimates were 0.47% (95% credible interval [CrI], 0.04%–0.89%), 0.25% (CrI, 0.03%–0.54%), and 0.23% (CrI, 0.04%–0.54%), respectively. No seropositive specimens had neutralizing antibodies.

Conclusions
Australia’s seroprevalence was extremely low (&lt;0.5%) after the only national COVID-19 wave thus far. These data and the subsequent limited community transmission highlight the population’s naivety to SARS-CoV-2 and the urgency of increasing vaccine-derived protection.
Recent advances in single-cell sequencing technologies
Authors: Wen Lu , Tang Fuchou 
Published: January 2022

Abstract
Single-cell omics sequencing was first achieved for the transcriptome in 2009, which was followed by fast development of technologies for profiling the genome, DNA methylome, 3D genome architecture, chromatin accessibility, histone modifications, etc., in an individual cell. In this review we mainly focus on the recent progress in four topics in the single-cell omics field: single-cell epigenome sequencing, single-cell genome sequencing for lineage tracing, spatially resolved single-cell transcriptomics and third-generation sequencing platform-based single-cell omics sequencing. We also discuss the potential applications and future directions of these single-cell omics sequencing technologies for different biomedical systems, especially for the human stem cell field.
Characterization of two-level system noise for a microwave kinetic inductance detector comprising niobium film on a silicon substrate
Authors: Sueno Y , Honda S , Kutsuma H , Mima S , Otani C , Oguri S , Suzuki J , Tajima O 
Published: January 2022

Abstract
A microwave kinetic inductance detector (MKID) is a cutting-edge superconducting detector. It comprises a resonator circuit constructed with a superconducting film on a dielectric substrate. To expand its field of application, it is important to establish a method to suppress the two-level system (TLS) noise that is caused by the electric fluctuations between the two energy states at the surface of the substrate. The electric field density can be decreased by expanding the strip width (S) and gap width from the ground plane (W) in the MKID circuit, allowing the suppression of TLS noise. However, this effect has not yet been confirmed for MKIDs made with niobium films on silicon substrates. In this study, we demonstrate its effectiveness for such MKIDs. We expanded the dimension of the circuit from (S, W) = (3.00 μm, 4.00 μm) to (S, W) = (5.00 μm, 23.7 μm), and achieved an increased suppression of 5.5 dB in TLS noise.