bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoimmunity
Authors: Rosen Antony 
Published: February 2020

Abstract
Autoimmune diseases occur when a sustained, specific, adaptive immune response is generated against self-components, and results in tissue damage or dysfunction. It is now clear that an autoimmune component is a feature of many human diseases. Indeed, there are some estimates that autoimmune diseases afflict more than 3% of Western populations, and imposes a significant personal and economic burden on individuals and nations. They probably affect more commonly women than men, and have peak incidence in the third to sixth decades. This chapter will illustrate many of the principles unifying various autoimmune states, and will present a conceptual framework within which to understand their aetiology, pathogenesis, and pathology. The rapid advances in knowledge being made in this group of disorders predict that disease mechanisms will soon be more clearly understood, and will greatly impact therapeutics.
The nature and development of cancer: Cancer mutations and their implications
Authors: Brenton James D. , Eisen Tim 
Published: February 2020

Abstract
Cancer is a genetic disease in which progressive accumulation of mutations in the genome of somatic cells induces abnormal biological capabilities. Cancer-inducing mutations may originate from single base substitutions or large chromosomal rearrangements; but ultimately they disrupt normal cellular processes by altering protein function or disturbing the regulation of gene expression. Loss-of-function mutations in tumour suppressor genes inactivate physiological control of cell processes, whereas gain-of-function mutations directly affect physiological networks and, for example, induce pathological activation of signalling pathways. For many common cancers, we are now close to defining unique sets of somatic alterations which confer a specific signature of the cancer type and are also highly specific to the individual patient.
Cancer immunity and immunotherapy
Authors: Drake Charles G. 
Published: February 2020

Abstract
The development of a cancer in an immunologically intact host leads to an interaction between the host immune system and the tumour mass. The three phases of tumour/host interactions (Elimination, Equilibrium, and Escape) form the ‘immune editing hypothesis’, which serves as a valuable framework for understanding of the immune response to cancer and the approaches by which this might be manipulated for therapeutic benefit. Immunotherapy is emerging as an important treatment modality for many tumour types, including melanoma, lung cancer, kidney cancer, lymphoma, and bladder cancer. By the time you read this chapter it is highly likely that additional monotherapy and combination regimens will be approved in multiple tumour types, but an understanding of the basic mechanisms underlying an adaptive antitumour immune response will be valuable in understanding future agents, as well as their toxicities.
Medical management of breast cancer
Authors: Crook Tim , Li Su , Harper Peter 
Published: February 2020

Abstract
Most patients with breast cancer are offered surgery, the main options being modified radical mastectomy, with or without immediate or delayed breast reconstruction, or breast-conserving surgery. All patients treated surgically for early breast cancer should be considered for risk-reducing neoadjuvant (before surgery) or adjuvant (after surgery) treatments. Adjuvant radiotherapy should be considered for all patients who have undergone breast-conserving surgery. Adjuvant medical therapies include (1) endocrine therapy—should be given to all oestrogen-receptor positive patients (premenopausal—tamoxifen; postmenopausal—aromatase inhibitors); (2) anti-HER2 targeted therapy (e.g. trastuzumab) in cancers that overexpress the HER2 oncogene; (3) chemotherapy—selection is informed by clinic-pathological parameters and increasingly by molecular genetic platforms such as Oncotype DX; patients with oestrogen-receptor negative, node-positive disease should receive regimens containing sequential anthracyclines and taxanes. Regimens for neoadjuvant treatment are similar to those used in the adjuvant setting.
Falls, faints, and fragility fractures
Authors: Kearney Fiona , Masud Tahir 
Published: February 2020

Abstract
Falls and their complications are the fifth leading cause of deaths in older adults. They typically result from the interplay of the environment, comorbidity, and age-related changes in postural stability. Recurrent falls can be debilitating in terms of physical consequences and in terms of the psychological impact of fear of falling, resulting in restriction of activity leading to a spiral of deconditioning, further loss of function, low mood, depression, and social isolation. Since some falls can be prevented, all older people in contact with healthcare professionals should be asked routinely whether they have fallen in the past year. Management requires a multifactorial approach, directed by the relevant contributors determined in the assessment process. The aim should be to prevent future falls and minimize their consequences, whilst avoiding imposing restrictions to the point that they negatively impact function, independence, and quality of life.
Symptoms other than pain
Authors: McQuillan Regina 
Published: February 2020

Abstract
Common symptoms in life-limiting illness include pain, fatigue, anorexia, nausea, constipation, and dyspnoea. These may be due to disease or disease progression, treatment side effects, an intercurrent acute problem, or comorbidity. Patients with life-limiting illnesses often have multiple comorbidities and might be on many medications. Effective treatment always depends on making as precise a diagnosis as possible (e.g. pharmacological management of nausea and vomiting is guided by the presumed mechanism). Symptoms can also herald an emergency (e.g. sepsis, delirium, spinal cord compression), when the patient’s frailty, likely prognosis, and own values and wishes need to be taken into account in planning management. Individualized assessment and decision-making are vital.
Clinical features and general management of patients with severe infections
Authors: Watkinson Peter , Young Duncan 
Published: February 2020

Abstract
This chapter examines how the host response to a severe infection involves an intricate link between the inflammatory and coagulation systems, and mechanisms designed to limit damage to normal tissues. Although originally describing both localized and disseminated infections, the term sepsis is now more commonly used to describe the systemic response to a severe infection. The symptoms and signs of sepsis include fever and rigors, flushing and vasodilation, an elevated heart and respiratory rate, confusion, hypotension, and oliguria. To these are added symptoms and signs relating to the specific infection site and pathogenic organism. The initial diagnosis of sepsis is largely clinical. The immediate treatment involves intravenous fluids, appropriate antibiotics and control of the source of infection. Culture results may allow refinement of antibiotic treatment. Treatment guidelines are available and updated regularly.
Nosocomial infections
Authors: Bowler Ian C.J.W. , Scarborough Matthew 
Published: February 2020

Abstract
Hospital-acquired or nosocomial infections—defined for epidemiological purposes as infections manifesting more than 48 hours after hospital admission—are common. They affect 1.4 million people worldwide, involve between 5 and 25% of hospitalized patients at any one time and are associated with considerable morbidity, mortality, and cost. The most common sites of nosocomial infection are the urinary tract, surgical wounds, and the lower respiratory tract. Most are bacterial in origin, the most common species being Escherichia coli, Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus), enterococci, Pseudomonas aeruginosa, and coagulase-negative staphylococci. The principal risk factors are extremes of age, the severity of underlying acute disease (e.g. neutropenia, organ system failure), and chronic medical conditions (especially diabetes, renal failure, and alcohol abuse).
Antimicrobial chemotherapy
Authors: Albur Maha , MacGowan Alasdair , Finch Roger G. 
Published: February 2020

Abstract
The practice of medicine changed dramatically with the availability of effective antimicrobial agents. Often fatal diseases, such as infective endocarditis, became treatable; much minor community infectious morbidity became readily controlled; for example, urinary tract infection; many surgical procedures became much safer, and developments in solid organ and bone marrow transplantation became possible. However, the very success of antimicrobial chemotherapy has led to anti-infective overuse and misuse. In some countries, antibiotics are freely available to the public for purchase ‘over the counter’, with few controls or guidance to ensure their safe and effective use. In many others there are poorly developed antimicrobial stewardship programmes. The emergence and spread of antimicrobial resistance worldwide and the decline in development and licensing of new antimicrobials over the last 30 years has threatened the future successful treatment of bacterial infections.
Immunization
Authors: Goldblatt David , Ramsay Mary 
Published: February 2020

Abstract
Immunization is one of the most successful medical interventions ever developed: it prevents infectious diseases worldwide. The basis for its success is that the human immune system can respond to vaccines by producing pathogen-specific antibody and memory cells (both B and T cells) which protect the body should the pathogen be encountered. Most currently licensed vaccines contain live or killed bacterial or viral constituents, bacterial polysaccharides, or bacterial toxoids, while new types of vaccines are being developed that contain DNA. Most vaccines are delivered directly into skin or muscle via needles, or they are administered orally. New edible vaccines and vaccines delivered via the skin without the use of needles are being developed. The Expanded Programme on Immunization, set up by the World Health Organization to define which vaccines should be delivered in resource-poor countries, has done much to increase vaccination coverage among infants most at risk of infectious diseases.
Herpesviruses (excluding Epstein–Barr virus)
Authors: Sissons J.G.P. 
Published: February 2020

Abstract
The Herpesviridae family is widely distributed in the animal kingdom. More than 100 have been isolated from humans, primates, and other mammals, and from reptiles and fish. Eight human herpesviruses, all with a linear double-stranded DNA genome and divided into alpha-, beta-, and gamma-subfamilies on the basis of genomic and biological properties, share the capacity to produce latent infection. The diseases they cause may result from primary infection, or reactivation of the virus from latency, and tend to be more severe in immunosuppressed patients. Diagnosis of the various herpesvirus infections may be made on clinical grounds alone, by culture or demonstration of viral particles by electron microscopy of relevant samples, by serological testing, or now more routinely by polymerase chain reaction-based tests.
Poxviruses
Authors: Smith Geoffrey L. 
Published: February 2020

Abstract
Poxviruses are large, complex DNA viruses that have played several seminal roles in medicine and biological science. Cowpox virus was introduced by Jenner as the first human vaccine in 1796; widespread vaccination with vaccinia virus led to the global eradication of smallpox in 1977, the only human disease to have been eradicated. Smallpox is caused by variola virus, the most infamous poxvirus. Other poxviruses include molluscum contagiosum, which is the only other poxvirus that infects only humans, causing benign skin tumours that may be single or multiple, typically persisting for months before undergoing spontaneous regression. The development of vaccinia virus as an expression vector pioneered the concept of using genetically engineered viruses as live vaccines. Vaccinia virus is also being developed as an oncolytic agent. Poxviruses remain excellent models for studying virus-host interactions and virus immune evasion strategies.
Mumps: Epidemic parotitis
Authors: Rima B.K. 
Published: February 2020

Abstract
Mumps is an acute, systemic, highly infectious, communicable infection of children and young adults, caused by a paramyxovirus (with an RNA genome). Transmission is by airborne droplet spread. After an incubation period of 14–18 days, typical presentation is with fever, pain near the angle of the jaw, and swelling of the parotid glands. Complications include orchitis, meningitis, and encephalitis. Diagnosis is obvious clinically in cases with a contact history and parotitis, but serological (mumps-specific IgM and IgA) and RNA-based (RT-PCR) tests are used when this is not the case (e.g. the patient presenting with meningitis). Treatment is symptomatic. Prevention is by vaccination, often given as one component of a trivalent mumps/measles/rubella vaccine at 14–16 months of age. A follow-up vaccination is now recommended at 4–5 years of age.
Measles
Authors: Whittle Hilton C. , Aaby Peter 
Published: February 2020

Abstract
Measles is a single-stranded RNA virus that is spread by aerosolized droplets and is highly transmissible. It causes a spectrum of disease ranging from mild in the well-nourished to severe in the malnourished or immunosuppressed: mortality is 3–10% in Africa. At around 10–14 days after infection, the viral prodrome typically consists of runny nose and fever, sometimes also diarrhoea or convulsions; signs include mild conjunctivitis, red mucosae, and (on the buccal mucosa) Koplik’s spots. After 14–18 days a morbilliform rash first appears on the forehead and neck, then spreads to involve the trunk and finally the limbs. Other manifestations include severe conjunctivitis (especially in those who are vitamin A deficient), pneumonitis and enteritis (which may cause profuse diarrhoea).
Enterovirus infections
Authors: Minor Philip , Desselberger Ulrich 
Published: February 2020

Abstract
Enteroviruses are single-stranded, positive-sense RNA viruses comprising poliomyelitis viruses (3 types), coxsackie A viruses (23 types), coxsackie B viruses (6 types), and echoviruses (33 types). They have recently been reclassified into four human enterovirus species (A–D) on the basis of sequence comparisons. Transmission is by the faeco-oral route, with marked seasonal peaks of infection in areas of temperate climate, but infections occurring all year round in tropical regions.
Following transmission, enteroviruses undergo a first round of replication in cells of the mucosal surfaces of the gastrointestinal tract and in gut-associated lymphoid cells, followed by viraemia, which leads to infection of distant organs (brain, spinal cord, meninges, myocardium, muscle, skin, and so on), where lesions might be produced. Shedding of virus occurs from throat and faeces for many weeks.
Virus infections causing diarrhoea and vomiting
Authors: Dormitzer Philip R. , Desselberger Ulrich 
Published: February 2020

Abstract
Acute gastroenteritis is frequently caused by rotaviruses, human caliciviruses (noroviruses, sapoviruses), astroviruses, and enteric adenoviruses (group F): these cause much disease worldwide and considerable mortality, mainly in developing countries. Other viruses found in the human gastrointestinal tract are not regularly associated with diarrhoeal disease, except in patients who are immunosuppressed and in whom herpes simplex virus, cytomegalovirus, and picobirnaviruses can cause diarrhoea, as can HIV itself. Following an incubation period of 1–2 days, there is sudden onset of watery diarrhoea lasting between 4 and 7 days, vomiting, and varying degrees of dehydration. Other features include abdominal cramps, headache, myalgia, and fever. Treatment is supportive, mainly with oral rehydration solutions or—in more severe cases—intravenous rehydration. Continued feeding is recommended, with zinc supplementation in areas where micronutrient deficiency may be present.
Flaviviruses excluding dengue
Authors: Lee Rossi Shannan , Vasilakis Nikos 
Published: February 2020

Abstract
The family Flaviviridae currently consists of four recognized genera: Flavivirus, Pestivirus, Hepacivirus, and Pegivirus. Although members of the family have a large host range that includes both vertebrates and invertebrates, only members of the genus Flavivirus are known as arboviruses, vectored either by mosquitoes or ticks. The remaining genera in the family are exclusively found in mammals, and their diversity has greatly expanded with recent virus discoveries. The genus Flavivirus comprises 92 virus species, of which over 40 can cause human infection. Many of these include important human pathogens such as Zika, dengue, yellow fever, West Nile, and Japanese encephalitis virus.
Bunyaviridae
Authors: Le Duc James W. , Bente D.A. 
Published: February 2020

Abstract
Viruses of the family Bunyaviridae are the largest family of RNA viruses with more than 350 named isolated. They contain a three-segmented, single-stranded, negative-sense RNA genome. They are divided into five genera, of which four are known to include human pathogens—Orthobunyavirus, Phlebovirus, Hantavirus, and Nairovirus. These viruses are found throughout the world and are transmitted between vertebrate hosts and to humans through the bite of infected arthropod vectors (mosquitoes, ticks, others), or from infectious excreta of rodents and other small mammals, and rarely person to person. Many are transmitted from infected arthropod vector females to the next generation by transovarial transmission, thereby surviving adverse environmental conditions and leading to marked seasonal distribution of disease. There are few vaccines or drugs available to protect against infection. Prevention is by avoidance of exposure to potentially infected arthropod and small mammal vectors.
Parvovirus B19
Authors: Brown Kevin E. 
Published: February 2020

Abstract
Parvovirus B19 (B19V) is a small DNA virus that replicates in erythroid progenitor cells, with virus-induced cytotoxicity stopping red cell production. It only infects humans, is endemic in most places, and is transmitted predominantly by the respiratory route. In healthy people it causes the rash illness, erythema infectiosum, also known as ‘fifth disease’ or ‘slapped cheek disease’, associated with minimal drop in haemoglobin, but in patients with increased red cell turnover (e.g. haemolytic anaemia or haemoglobinopathy), it causes transient aplastic crisis; in immunocompromised patients it causes chronic anaemia; and following maternal infection it leads to hydrops fetalis or fetal loss. Treatment is supportive in most instances, but reduction in iatrogenic immunosuppression and/or intravenous immunoglobulin may be appropriate in some cases. No vaccine is available.
Hepatitis viruses (excluding hepatitis C virus)
Authors: Cramp Matthew , Dhanda Ashwin , Naoumov Nikolai V. 
Published: February 2020

Abstract
Viral hepatitis is an ancient disease which remains a major health problem worldwide. The group of hepatitis viruses includes five unrelated human viruses (A to E), which differ in their genome organization, biology, and epidemiology, while being united by their hepatotropism. About 10–15% of cases of viral hepatitis are considered as non-A to E hepatitis, whose aetiology is still unknown, but the search for which has led to the identification of several new viruses (e.g. hepatitis G virus or GB virus-C, TT, and SEN viruses) of uncertain pathogenic significance. Thus, the search for new hepatitis agents responsible for the small proportion of cases with cryptogenic hepatitis continues.
Viruses and cancer
Authors: Weiss Robin A. 
Published: February 2020

Abstract
Viruses are important in cancer for three main reasons: as a cause of cancer—about 15% of the worldwide cancer burden is due to viruses; in understanding of the biology of cancer-through the discovery and characterization of oncogenes and tumour suppressor genes; and in the treatment of cancer—some viruses selectively replicate in and destroy proliferating cells, viruses as foreign antigens may aid the recognition of cancer cells by the host’s immune system (‘xenogenization’), and viruses can also be used as vectors for immunization and for gene therapy. Viral cancers are prevented by early screening for tumours, screening for the virus in order to prevent transmission, and immunization as in the cases of hepatitis B virus and human papilloma virus.
Diphtheria
Authors: Bethell Delia B. , Hien Tran Tinh 
Published: February 2020

Abstract
Diphtheria is a potentially lethal infection caused by toxin-producing strains of Corynebacterium diphtheria, a Gram-positive bacillus. Humans are the only known reservoir, with spread via respiratory droplets or direct contact with skin lesions. Although now rare in developed countries, this vaccine-preventable disease remains an important problem in countries with poor or failing health systems, and is estimated to cause about 5,000 deaths per year worldwide, most in children under 5 years of age. Diphtheria develops when toxigenic bacteria lodge in the upper airway or on the skin of a susceptible individual. An intense inflammatory reaction develops, leading to a characteristic greyish-coloured pseudomembrane that is adherent to underlying tissues. Systemic effects are caused by release of diphtheria toxin, carried by a lysogenic corynebacteriophage, a single molecule of factor A of which can kill a eukaryotic cell.
Staphylococci
Authors: Popovich Kyle J. , Weinstein Robert A. , Hota Bala 
Published: February 2020

Abstract
This chapter looks at staphylococci, which are Gram-positive cocci that form clusters, but can occur singly, in pairs, chains, or tetrads. They are classically distinguished from other Gram-positive cocci by presence of catalase, an enzyme that degrades hydrogen peroxide (H2O2). S. aureus is distinguished from other coagulase-negative staphylococci, which are generally less virulent, by the presence of coagulase, an enzyme that coagulates plasma. Many toxins and regulatory elements enhance virulence in staphylococci. Staphylococci are skin commensals. About 20% of adults are persistently colonized by S. aureus, 60% are intermittently colonized, and 20% are never colonized. High-risk groups for S. aureus colonization include infants, insulin-dependent diabetics, intravenous drug users, HIV-infected patients, and renal dialysis patients. Methicillin-resistant Staphylococcus aureus (MRSA) was once predominantly seen in hospitals. However, over the past twenty years the epidemiology of MRSA has significantly changed, with MRSA infections now being observed in community settings.
Neisseria gonorrhoeae
Authors: Sherrard Jackie , Unemo Magnus 
Published: February 2020

Abstract
Neisseria gonorrhoeae is a Gram-negative, intracellular diplococcus that is transmitted by direct inoculation of infected secretion from one mucosa to another. It primarily colonizes the columnar epithelium of lower genital tract, only occasionally spreading to the upper genital tract or causing systemic disease. Oropharyngeal and rectal infections are common in men who have sex with men but also occur in women. N. gonorrhoeae is almost exclusively transmitted by sexual activity. Oropharyngeal and rectal infections usually produce no symptoms; disseminated gonococcal infection is a comparatively benign bacteraemia affecting joints (particularly shoulder and knee) and skin; traditionally more common in women than men. The gonococcus has adapted rapidly to prevalent antimicrobial usage, leading to resistance to all antibiotics used for treatment, notably penicillins, fluoroquinolones, macrolides, tetracycline, and cephalosporins. This development has resulted in major concerns internationally and the introduction of international and national action/response plans as well as dual antimicrobial therapy.