bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lyme borreliosis
Authors: Wormser Gary P. , Nowakowski John , Nadelman Robert B. 
Published: February 2020

Abstract
Lyme borreliosis is a zoonotic bacterial infection caused by Borrelia burgdorferi sensu lato, a spirochaetal agent transmitted by certain species of Ixodes ticks. Small rodents and birds serve as reservoirs. It is the most common vector-borne infection in the United States of America and an important infection in many countries throughout the temperate regions of Europe and northern Asia, where a wider variety of borrelia species account for differences in clinical manifestations in Eurasia compared with the United States. The most common and earliest clinical manifestation is erythema migrans, a distinctive cutaneous lesion that occurs at the site of deposition of the spirochaete by the vector tick. Most people treated for Lyme borreliosis respond well to a 2-week course of antibiotic therapy. Symptomatic treatment is recommended for patients who have or develop subjective complaints of unclear aetiology despite successful resolution of the objective manifestation of Lyme borreliosis following antibiotic therapy.
Nonvenereal endemic treponematoses: Yaws, endemic syphilis (bejel), and pinta
Authors: Marks Michael , Mitjà Oriol , Mabey David 
Published: February 2020

Abstract
The endemic treponematoses are chronic, granulomatous diseases caused by morphologically and serologically identical spirochaetes of the genus Treponema. They are spread by intimate but non-sexual contact and possibly by fomites, mainly among children. Treponema pallidum subsp. pertenue causing yaws (framboesia), T. pallidum subsp. endemicum causing endemic syphilis (bejel) and T. carateum causing pinta (carate) are distinguishable from T. pallidum subsp. pallidum, causing venereal syphilis, by their epidemiology and pathological effects and genomic structure (e.g. the arp gene). Despite the successful WHO/UNICEF mass penicillin treatment campaign (1952–1964), there has been a resurgence of yaws, mainly in West Africa, Southeast Asia, and the Pacific. Children living in rural areas in warm, humid climates in tropical countries are most affected by yaws. About 10% of untreated cases develop late, disfiguring, or crippling lesions of skin, bone, and cartilage.
Listeriosis
Authors: Hof Herbert 
Published: February 2020

Abstract
Listeriosis is caused by the Gram-positive bacillus Listeria monocytogenes, whose natural habitat is the soil. Consumption of soft cheeses, other dairy products, meat products, seafood, and vegetables is the principal route of infection. Patients at particular risk include those who are immunocompromised, very young, or very old. Pregnant women are also at risk, although they develop only mild disease, but the bacteria can be transmitted to the child either in utero or during birth, causing serious systemic disease. The disease varies from a mild, influenza-like illness to fatal septicaemia and meningoencephalitis. Purulent, localized infections of any organ are sometimes seen. Aside from supportive care, the usual treatment of choice is high-dose intravenous ampicillin, which must be administered for at least 2 weeks. The prognosis is poor, with mortality of up to 30%. Prevention depends upon those that are vulnerable avoiding high-risk foods. There is no vaccine.
Bartonellas excluding B. bacilliformis
Authors: Chomel Bruno B. , Boulouis Henri-Jean , Stuckey Matthew J. , Rolain Jean-Marc 
Published: February 2020

Abstract
Bartonellae are Gram-negative bacilli or coccobacilli belonging to the α-2 subgroup of Proteobacteria. A given Bartonella species usually persists within a given mammalian host, with transmission between hosts by haematophagous arthropods. A single species, such as B. henselae or B. quintana, can cause acute or chronic infection, with vascular, proliferative, or suppurative features depending on the host’s immune response. Many new Bartonella species isolated from various mammals have been identified as zoonotic.
Cat-scratch disease—caused by B. henselae and commonly associated with a cat scratch, presents with a discrete papule or vesicle typically developing at the site within a week, followed by regional lymphadenopathy, sometimes with fever and constitutional symptoms. Disseminated infection can cause neuro-retinitis and (rarely) encephalopathy.
Chlamydial infections
Authors: Horner Patrick , Mabey David , Taylor-Robinson David , Unemo Magnus 
Published: February 2020

Abstract
Chlamydiae are pathogenic bacteria that likely evolved from host-independent, Gram-negative ancestors. Chlamydiae depend on a eukaryotic host cell for their replication which takes place in an inclusion inside the host cell, and for their dispersal, cell lysis, or extrusion subsequently occurs. Although the phylum Chlamydiae (order Chlamydiales) was originally thought to only contain one family, the Chlamydiaceae, a total of nine families are now recognized. The genus Chlamydia remains the most widely studied. The species Chlamydia trachomatis was proposed some decades ago on the basis of 16S rRNA and 23S rRNA sequences, to belong to the genus Chlamydia together with C. muridarum and C. suis. This chapter primarily focuses on the species C. trachomatis, which causes disease of ocular trachoma (serovars A–C), oculo-anogenital tract infection (serovars D–K) and lymphogranuloma venereum (serovars L1–L3). However, infections caused by C. pneumoniae and C. psittaci are also discussed.
Amoebic infections
Authors: Knight Richard 
Published: February 2020

Abstract
Two very different groups of amoebic species infect humans. (1) Obligate anaerobic gut parasites, including the major pathogen Entamoeba histolytica, which causes amoebic dysentery and amoebic liver abscess. Infection is especially common in Mexico, South America, Africa and South-east Asia; nearly all cases in temperate countries is acquired elsewhere. Other gut amoebae are Dientamoeba fragilis (which causes relatively mild colonic involvement with diarrhoea), and eight non-pathogenic species including Entamoeba dispar. (2) Aerobic free-living, water and soil amoebae– Naegleria, Acanthamoeba and Balmuthua, which can become facultative tissue parasites in humans after cysts or trophozoites are inhaled, ingested, or enter damaged skin, cornea or mucosae: they may cause primary amoebic meningo-encephalitis, amoebic keratitis or brain abscess.
Babesiosis
Authors: Brasseur Philippe 
Published: February 2020

Abstract
Babesia are intraerythrocytic, tick-transmitted, protozoan parasites that infect a broad range of wild and domesticated mammals including cattle, horses, dogs, and rodents. Human babesial infection is uncommon, mainly caused by B. microti in North America and B. divergens in Europe, with most infections occurring in asplenic people. Presentation is typically with non-specific ‘viral-type’ symptoms. Haemolytic anaemia is a characteristic feature and can be severe, particularly with B. divergens. Diagnosis is by discovering babesia organisms in Giemsa-stained blood smears, or detection of its DNA in blood by polymerase chain reaction. Aside from supportive care, treatment is usually with combinations of clindamycin and quinine or atovaquone and azithromycin. Mortality ranges from 5 to 40%. Prevention is by use of repellents, removing ticks from the skin, and avoidance of exposure in asplenic and immunocompromised individuals: there is no vaccine.
Guinea worm disease (dracunculiasis)
Authors: Knight Richard 
Published: February 2020

Abstract
Guinea worm disease (dracunculiasis)—now limited to sub-Saharan Africa—is caused by the nematode Dracunculus medinensis, whose life cycle involves aquatic copepod crustaceans. Humans are infected when they drink water containing infective larvae. Adult worms enter subcutaneous tissue and can reach a metre in length. Clinical presentation is usually with a skin blister, most often on the leg, sometimes preceded by allergic prodromal symptoms. Bacterial infection and local scarring with disability are common complications. Most patients in endemic areas recognize their condition, but irrigation of ulcers can reveal larvae. Treatment is by physical removal of the worm; anthelmintics have no role in management. Provision of safe water for drinking is the key to prevention. The disease is now nearing eradication.
Schistosomiasis
Authors: Dunne David , Vennervald Birgitte 
Published: February 2020

Abstract
Schistosomiasis is caused by trematode worms Schistosoma spp., whose life cycle requires a definitive vertebrate host and an intermediate freshwater snail host. Transmission to humans occurs through exposure to fresh water containing infectious larvae, which can penetrate intact skin before developing into blood-dwelling adult worms. The disease is patchily distributed in parts of South America, Africa, the Middle East, China, and Southeast Asia, with about 200 million people infected and 20 million suffering severe consequences of infection. Most infected people living in endemic areas have few (if any) overt symptoms, but clinical manifestations (when present) depend on the stage of infection. Praziquantel is the drug of choice, with corticosteroids added in cases of Katayama fever. Acute schistosomiasis responds well, but chronic disease less so, but rapid re-exposure and reinfection are common (particularly in young children) unless control measures are implemented at the community level.
Podoconiosis (nonfilarial elephantiasis)
Authors: Davey Gail 
Published: February 2020

Abstract
Podoconiosis is the lesser-known of the two major forms of tropical lymphoedema. The disease affects genetically susceptible individuals who go barefoot and whose feet and legs are exposed long term to red clay soils. It is found focally across tropical Africa, Central America, and north India where such soils coexist with high altitude, high rainfall, and low-income populations. Prodromal symptoms include itching and a burning sensation in the foot; early changes include spreading or ‘splaying’ of the forefoot and leakage of colourless ‘lymph’ fluid. Later stages are manifested by lymphoedema, which is usually bilateral and limited to below the knee. Studies examining host immunological and inflammatory responses are currently underway to improve possible future treatment options for the disease.
Minerals and trace elements
Authors: Younger Katherine 
Published: February 2020

Abstract
The essential minerals, calcium, phosphorus, potassium, sulphur, sodium, chlorine, and magnesium (macrominerals) and trace elements chromium, copper, fluorine, iodine, magnesium, manganese, molybdenum, phosphorus, selenium, and zinc, have diverse and critical functions in human metabolism. Dietary sources and the intake requirements for macrominerals and trace elements for optimal physiological well-being have been established, and the upper range of intake has been also been set so that unwanted or even toxic effects can be avoided. Deficiency of certain trace elements contributes importantly to the global burden of illness and mortality, especially in infants under the age of five years. An up-to-date familiarity with the scientific basis of mineral and trace element physiology is therefore critical for maintaining good standards of clinical practice and to inform the best standards of nutritional advice, especially in the treatment of severe illnesses associated with deficiency or toxic excess of one or more macrominerals or trace elements.
The inborn errors of metabolism: General aspects
Authors: Cox Timothy M. , Watts Richard W.E. 
Published: February 2020

Abstract
The inborn errors of metabolism are those inherited diseases in which the phenotype includes a characteristic constellation of biochemical abnormalities related to an alteration in the catalytic activity of a single specific enzyme, activator, or transport protein. Mechanism of diseases—mutations in the proteins giving rise to the inborn errors of metabolism affect primary, secondary, tertiary, or quaternary structure. This can lead to an enormous variety of consequences. Clinical presentation—the manifestations of metabolic disease are protean and may seem nondescript, especially in adults, hence a high level of suspicion may be required to make a correct diagnosis. Prevention and screening—there is a strong case for mass population screening for some inborn errors of metabolism at the presymptomatic stage to allow early detection and introduction of proven treatment before irreversible damage occurs. Management—definitive cure of the underlying abnormality is available for a few disorders, but precise characterization of the biochemical disturbance often permits rational treatment to be organized and provides the basis for further therapeutic endeavours. General approaches include (1) restriction of a substrate that cannot be metabolized including molecules derived from the diet; (2) replacement of a missing metabolic product; (3) removal of poisonous metabolites or rebalancing overproduction of toxic intermediates; (4) administering pharmacological doses of a cofactor, sometimes a vitamin, that may also stabilize a mutant enzyme; (5) replacement of a missing gene product, usually by enzymatic augmentation therapy or pharmacological chaperones, to prevent premature aggregation and denaturation; (6) repression of an overproduced protein or metabolite by stable RNA inhibition; (7) transplantation of cells or organs as a ‘gene replacement therapy’; and (8) activation of a poorly functioning protein.
Protein-dependent inborn errors of metabolism
Authors: Hoffmann Georg F. , Kölker Stefan 
Published: February 2020

Abstract
Protein-dependent inborn errors of metabolism are caused by inherited enzyme defects of catabolic pathways or intracellular transport of amino acids. Most result in an accumulation of metabolites upstream of the defective enzyme (amino acids and/or ammonia), causing intoxication. Protein-dependent metabolic diseases usually have a low prevalence except for some high-risk communities with high consanguinity rates. However, the cumulative prevalence of these disorders is considerable (i.e. at least &gt;1:2000 newborns) and represents an important challenge for all public health systems. Types and clinical presentation of protein-dependent inborn errors of metabolism—this chapter discusses amino acid disorders, organic acid disorders, and urea cycle defects. The disease spectrum is broad, but follows a distinct pattern in specific disorders. Investigation and management—every infant presenting with symptoms of unexplained metabolic crisis, intoxication, or encephalopathy requires urgent evaluation of metabolic parameters, including analyses of arterial blood gases, serum glucose and lactate, plasma ammonia and amino acids, acylcarnitine profiling in dried blood spots, and organic acid analysis in urine. This chapter discusses the basic principles of acute emergency therapy and of long-term treatment, which aims principally to mitigate the metabolic consequences of enzyme deficiencies by compensating for them. Successful treatment of affected individuals is often difficult to achieve. Careful supervision in metabolic centres involving an experienced multidisciplinary team is invaluable for the best outcome.
Inborn errors of fructose metabolism
Authors: Cox Timothy M. 
Published: February 2020

Abstract
Most people in developed countries ingest 50 to 100 g fructose equivalents daily in their diet, arising from fructose itself, sucrose, and sorbitol. After rapid carrier-mediated absorption across the intestinal epithelium, fructose is metabolized (mainly in the liver) by the enzymes ketohexokinase (fructokinase), aldolase B, and triokinase, eventually being converted into glucose or glycogen. Dietary sugars—burgeoning constituents in food and drinks worldwide—have undesirable effects on those with limited capacity to metabolize fructose, including severe illness or death in young patients. ‘Fructose malabsorption’ describes incomplete absorption of fructose that is associated with abdominal symptoms and diarrhoea reminiscent of intestinal disaccharidase deficiency. Symptoms occur after ingestion of fructose- or sorbitol-rich foods and drinks such as apple juice, but as yet a convincing genetic cause for this condition has not been found. Symptoms improve when the offending sugars are avoided. Three inborn errors of fructose metabolism are recognized and these disorders are vivid examples of gene–environment interactions: (1) essential or benign fructosuria due to fructokinase deficiency—a very rare disorder with apparently no ill effects; (2) hereditary fructose intolerance (fructosaemia)—an autosomal recessive disease caused by deficiency of aldolase B; and (3) fructose-1,6-diphosphatase deficiency —a very rare disease of infancy and childhood associated with failure of hepatic gluconeogenesis causing bouts of severe hypoglycaemia, ketosis, and lactic acidosis provoked by infection and starvation.
The porphyrias
Authors: Cox Timothy M. 
Published: February 2020

Abstract
The porphyrias are a remarkable family of metabolic disorders characterized biochemically by overproduction of haem precursors, principally in the liver and bone marrow. The acute porphyrias are inborn errors of varying penetrance that affect enzymatic steps in a tightly regulated biosynthetic pathway for haem; nonacute acquired forms also occur in genetically predisposed individuals. Clinical presentation of acute porphyria—life-threatening neurovisceral attacks occur in four of the porphyrias: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and Doss’ porphyria (5-aminolaevulinate dehydratase deficiency). These present with abdominal pain, psychiatric symptoms, and signs of sympathetic and hypothalamic autonomic overactivity, sometimes accompanied by convulsions and motor and sensory deficits. Diagnosis of acute porphyria—this is key to survival of an acute attack of porphyria, which can be suspected on the basis of the past history, in particular of photosensitivity or the intermittent discoloration of urine, and family history, and is confirmed by finding excess water-soluble haem precursors in urine. Management of acute porphyria—treatment of an acute porphyric attack mandates immediate withdrawal of inappropriate drugs and other precipitating factors; infusions of haem arginate or other licensed preparations of haem shorten life-threatening episodes and may be effective prophylaxis for recurrent porphyria in women with periodic attacks. The nonacute porphyrias are photosensitivity syndromes caused by excess photoactive macrocyclic porphyrins triggered especially by visible light in the blue–violet range. In the most severe form, manifestations are of severe blistering lesions on sun-exposed skin, particularly of the hands and face, with the formation of vesicles and bullae that may become infected. Healing may lead to loss of digits, scarring of the eyelids, nose, lips, and scalp, and occasionally blindness due to corneal scarring.
Lipid disorders
Authors: Cegla Jaimini , Scott James 
Published: February 2020

Abstract
High blood cholesterol and high blood triglycerides are causal risk factors for atherosclerotic cardiovascular disease, which remains the leading cause of death in the developed world. Lipid and lipoprotein metabolism—cholesterol, triglycerides, and fat-soluble vitamins are transported with specific proteins in the blood as multimeric complexes called lipoproteins. Lipid and lipoprotein metabolism are effected by three principal physiological processes: (1) intestinal absorption of dietary lipid and transport in the blood of dietary lipid and lipids, principally derived from the liver (as triglyceride-rich lipoproteins) to peripheral tissues for catabolism by skeletal and cardiac muscle or storage in adipose tissue; (2) return of triglyceride-rich lipoprotein remnants to the liver, hepatic synthesis of low-density lipoprotein, and the transport of cholesterol between peripheral tissues and the liver; and (3) reverse cholesterol transport by high-density lipoprotein (HDL) between peripheral tissues and the liver. Dyslipidaemias are disorders of lipoprotein metabolism in which there is elevation of total cholesterol and/or triglycerides, often accompanied by reduced levels of HDL cholesterol. Causes of dyslipidaemia—particular lipid disorders including polygenic hypercholesterolaemia, familial hypercholesterolaemia, combined hypercholesterolaemia and hypertriglyceridaemia, familial combined hyperlipidaemia, familial dysbetalipoproteinaemia (also called type 3 hyperlipoproteinaemia), and severe hypertriglyceridaemia, as well as secondary or aggravating factors. Management of dyslipidaemia—the key questions are: (1) what classes of lipoproteins and lipids are increased or decreased in the patient’s plasma? (2) Does the patient has a primary (genetic) or secondary (acquired) dyslipidaemia (often contributions from both influences)? (3) Is the patient at risk of atherosclerotic cardiovascular disease or acute pancreatitis? (4) What other risk factors (e.g. hypertension or diabetes) are present? (5) What treatments might be used to address these abnormalities?
Hereditary haemochromatosis
Authors: Griffiths William J.H. , Cox Timothy M. 
Published: February 2020

Abstract
Hereditary haemochromatosis syndromes are inherited disorders whereby inappropriate absorption of iron by the small intestine leads to iron deposition in the viscera, endocrine organs, and other sites, causing structural injury and impaired function. The most common form is classical adult (HFE-related) haemochromatosis, but other forms are recognized. Extended genetic platforms are increasingly used for specific diagnosis and noninvasive methods are increasingly used to evaluate hepatic damage. The mainstay of treatment is venesection although iron chelation therapy is an emerging oral alternative. Unravelling the molecular genetics of haemochromatosis is underpinning promising new therapies for disorders of iron homeostasis. Classical adult (HFE-related) haemochromatosis: aetiology and pathogenesis—inherited as a recessive trait and due to mutations in the major histocompatibility complex class I-related HFE gene that appear to reduce liver production of hepcidin. The principal mutant allele of HFE, designated C282Y, is carried by approximately 1 in 10 individuals of European ancestry, hence around 1 in 200 are homozygotes, usually with biochemical abnormalities of iron storage that may lead to full-blown clinical haemochromatosis. Clinical features—expression of disease may range from slight abnormalities of blood parameters that reflect iron metabolism to the established clinical syndrome of cutaneous pigmentation, cardiomyopathy, endocrine failure (especially diabetes mellitus and hypogonadism), arthritis, and pigment cirrhosis. Diagnosis—usually established by demonstrating abnormalities of iron metabolism. Molecular analysis of the HFE gene, in particular for homozygosity for the C282Y allele, is confirmatory. Management and prognosis—this is directed to the removal of iron by phlebotomy until the serum ferritin concentration is reduced to within the low normal range, after which the frequency of phlebotomy is reduced. Family members—first-degree relatives should be offered screening.