bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccine Effectiveness Against Influenza Hospitalization Among Children in the United States, 2015–2016
Authors: Feldstein Leora R , Ogokeh Constance , Rha Brian , Weinberg Geoffrey A , Staat Mary A , Selvarangan Rangaraj , Halasa Natasha B , Englund Janet A , Boom Julie A , Azimi Parvin H , Szilagyi Peter G , McNeal Monica , Harrison Christopher J , Williams John V , Klein Eileen J , Sahni Leila C , Singer Monica N , Lively Joana Y , Payne Daniel C , Fry Alicia M , Patel Manish , Campbell Angela P 
Published: February 2020

Abstract

Background
Annual United States (US) estimates of influenza vaccine effectiveness (VE) in children typically measure protection against outpatient medically attended influenza illness, with limited data evaluating VE against influenza hospitalizations. We estimated VE for preventing laboratory-confirmed influenza hospitalization among US children.

Methods
We included children aged 6 months–17 years with acute respiratory illness enrolled in the New Vaccine Surveillance Network during the 2015–2016 influenza season. Documented influenza vaccination status was obtained from state immunization information systems, the electronic medical record, and/or provider records. Midturbinate nasal and throat swabs were tested for influenza using molecular assays. We estimated VE as 100% × (1 – odds ratio), comparing the odds of vaccination among subjects testing influenza positive with subjects testing negative, using multivariable logistic regression.

Results
Of 1653 participants, 36 of 707 (5%) of those fully vaccinated, 18 of 226 (8%) of those partially vaccinated, and 85 of 720 (12%) of unvaccinated children tested positive for influenza. Of those vaccinated, almost 90% were documented to have received inactivated vaccine. The majority (81%) of influenza cases were in children ≤ 8 years of age. Of the 139 influenza-positive cases, 42% were A(H1N1)pdm09, 42% were B viruses, and 14% were A(H3N2). Overall, adjusted VE for fully vaccinated children was 56% (95% confidence interval [CI], 34%–71%) against any influenza-associated hospitalization, 68% (95% CI, 36%–84%) for A(H1N1)pdm09, and 44% (95% CI, –1% to 69%) for B viruses.

Conclusions
These findings demonstrate the importance of annual influenza vaccination in prevention of severe influenza disease and of reducing the number of children who remain unvaccinated or partially vaccinated against influenza.
Nonsurgical management of an asymptomatic popliteal venous aneurysm
Authors: Bajaj Vinay , Benavides Francisco , Fisher Jay 
Published: February 2020

Abstract
An 81-year-old male with a history of poorly controlled congestive heart failure, chronic obstructive pulmonary disease and atrial fibrillation among other comorbidities was admitted to the hospital for worsening bilateral leg swelling and cellulitis. The patient had an injury to his left medial malleolus 2 weeks prior, which failed outpatient care. During the physical exam, a soft mobile mass was palpated in the right popliteal fossa along with bilateral varicose veins, +1 pitting edema in bilateral lower extremities up to mid-calf. Duplex ultrasound revealed a saccular dilation in the right popliteal vein measuring 2.2 × 1.8 × 2.8 cm, without any evidence of superficial or deep vein thrombosis. After an extended conversation with the patient and his care team, a decision to continue with medical management with close monitoring was made. Follow-up ultrasounds performed at 1, 6 and 12 months show no changes.
Value of evidence in the rare type match problem: common source versus specific source
Authors: Van Dorp I N , Leegwater A J , Alberink I , Jongbloed G 
Published: February 2020

Abstract
In the so-called rare type match problem, the discrete characteristics of a crime stain have not been observed in the set of background material. To assess the strength of evidence, two competing statistical hypotheses need to be considered. The formulation of the hypotheses depends on which identification of source question is of interest (Ommen, 2017, Approximate statistical solutions to the forensic identification of source problem. (Phd thesis). South Dakota State University). Assuming that the evidence has been generated according to the beta-binomial model, two quantifications of the value of evidence can be found in the literature, but no clear indication is given when to use either of these. When the likelihood ratio is used to quantify the value of evidence, an estimate is needed for the frequency of the discrete characteristics. The central discussion is about whether or not one of the traces needs to be added to the background material when determining this estimate. In this article it is shown, using fully Bayesian methods, that one of the values of evidence from the literature corresponds to the so-called ‘identification of common source’ problem and the other to the ‘identification of specific source’ problem (Ommen, 2017, Approximate statistical solutions to the forensic identification of source problem. (Phd thesis). South Dakota State University). This means that the question whether or not one of the traces needs to be added to the background material reduces to the question whether a common source or specific source problem is under consideration. The distinction between the two values is especially important for the rare type match problem, since the values of evidence differ most in this situation.
Fostering medical and health research in resource-constrained countries
Authors: Makgoba Malegapuru W. , Tollman Stephen M. 
Published: February 2020

Abstract
Access to quality healthcare and education for all are essential elements underpinning national development as well as prerequisites for personal well-being. This makes it important to grasp the inequalities that still prevail in human and institutional capacity, including access to and use of research resources. The goals of fostering medical research in resource-constrained countries are to bring outstanding science to bear on their medical and health problems; invest in building the requisite medical and health research systems; develop an evidence base to inform policies and programmes, resource allocation, and health practice; enhance scientific processes, findings, explanation, and ‘discovery’ by drawing on local know-how; and gain sustained engagement with policymakers, senior managers, and community leaders.
Lysosomal disease
Authors: Deegan Patrick B. , Cox Timothy M. 
Published: February 2020

Abstract
The lysosome is a ubiquitous, single membrane-bond intracellular organelle which continuously recycles biological macromolecules: it not only breaks down cell components but has a dynamic role in nutrient and energy sensing that, through regulatory signalling, is critical for homeostasis and metabolic economy of the cell. More than 80 lysosomal diseases caused by single gene defects are known. Biochemical classification identifies (1) sphingolipidoses; (2) mucopolysaccharidoses; (3) glycoproteinoses; (4) glycogenosis, with or without lysosomal debris derived from subcellular organelles due to impaired autophagy; and (5) miscellaneous conditions with multiple classes of storage material such as the neuronal ceroid lipofuscinoses. Functional classification describes deficiency of (1) a specific acid hydrolase activity, (2) an activator protein, (3) a lysosomal membrane protein or transporter, or (4) abnormal post-translational modification of lysosomal proteins, and (5) abnormal biogenesis of lysosomes. A unified classification will emerge from genetic characterization integrated with clinicopathological manifestations of the individual disorders. Fabry’s and Gaucher’s diseases (glycosphingolipidoses) are probably the most frequent in the general population, but certain lysosomal diseases are over-represented in particular groups where consanguinity or endogamy is high. Other diseases discussed in this chapter include (1) cystinosis, (2) the mucopolysaccharidoses, (3) Pompe’s disease (glycogen storage disease type II), (4) Niemann–Pick diseases, (5) lysosomal acid lipase deficiency, (6) Danon’s disease, and (7) diseases more recently attributed to primary defects in lysosomes and related organelles.
Disorders of peroxisomal metabolism in adults
Authors: Wierzbicki Anthony S. 
Published: February 2020

Abstract
The peroxisome is a specialized organelle which employs molecular oxygen in the oxidation of complex organic molecules including lipids. Enzymatic pathways for the metabolism of fatty acids, including very long-chain fatty acids (VLCFAs), enable this organelle to carry out β-oxidation in partnership with mitochondria. A peroxisomal pathway for isoprenoid lipids derived from chlorophyll, such as phytanic acid, utilizes α-oxidation, but a default mechanism involving ω-oxidation may also metabolize phytanic acid and its derivatives. The biochemical manifestations, molecular pathology, and diverse clinical features of many peroxisomal disorders have now been clarified, offering the promise of prompt diagnosis, better management, and useful means to provide appropriate genetic counselling for affected families. At the same time, specific treatments including rigorous dietary interventions and plasmapheresis to remove undegraded toxic metabolites offer credible hope of improvement and prevention of disease in affected individuals. X-linked adrenoleukodystrophy (X-ALD)—due to mutations in the gene for an ATP-binding cassette (ABC) protein of unknown function and characterized by accumulation of unbranched saturated VLCFAs, particularly hexacosanoate (C26), in the cholesterol esters of brain white matter, adrenal cortex, and certain sphingolipids of the brain. The disease has multiple phenotypes. Most cases develop increasing handicap; management is palliative and supportive in most instances. Adult Refsum’s disease—due in most cases to mutations in the gene for phytanoyl-CoA hydroxylase (PHYH) such that patients are unable to detoxify phytanic acid by α-oxidation and have greatly elevated levels of this in their plasma. Usually presents in late childhood with progressive deterioration of night vision, the occurrence of progressive retinitis pigmentosa, and anosmia. Treatment is by restriction of dietary phytanic acid, with or without its elimination by plasmapheresis or apheresis.
α1-Antitrypsin deficiency and the serpinopathies
Authors: Lomas David A. 
Published: February 2020

Abstract
α1-Antitrypsin is an acute phase glycoprotein synthesized by the liver that functions as an inhibitor of a range of proteolytic enzymes, most importantly neutrophil elastase in the lung. Ninety-five per cent of severe plasma deficiency of α1-antitrypsin results from homozygosity for the Z allele (Glu342Lys), which causes the protein to undergo a conformational transition and form ordered polymers that are retained within hepatocytes as periodic acid–Schiff-positive, diastase-resistant inclusions. Clinical features— all adults homozygous for the Z allele of α1-antitrypsin have a minor degree of portal fibrosis that is often subclinical, but up to 50% have clinically evident cirrhosis and occasionally hepatocellular carcinoma. They also develop panlobular emphysema that typically affects the lung bases and is greatly exacerbated by smoking. Cor pulmonale and polycythaemia are late features. Diagnosis and management—severe genetic deficiency of α1-antitrypsin is readily diagnosed by low plasma levels and the virtual absence of the α1-band on protein electrophoresis. Patients should abstain from smoking and avoid agents that cause hepatic injury, such as excessive alcohol and obesity. Emphysema is treated along conventional lines. α1-Antitrypsin replacement therapy is widely used in North America to slow the progression of the lung disease and has recently been licensed by the European Medicines Agency, but its clinical efficacy remains contentious and it has no effect on liver disease. Clinical trials are underway to ‘knock down’ the expression of mutant Z α1-antitrypsin within hepatocytes to try to prevent cirrhosis. Other serpinopathies—the polymerization that underlies α1-antitrypsin deficiency is found in other members of the serine protease inhibitor (or serpin) superfamily to cause diseases as diverse as thrombosis (antithrombin), angio-oedema (C1 inhibitor), and dementia (neuroserpin).
Parathyroid disorders and diseases altering calcium metabolism
Authors: Thakker R.V. 
Published: February 2020

Abstract
The control of body calcium involves a balance—chiefly under the control of parathyroid hormone (PTH)—between the amounts that are absorbed from the gut, deposited into bone and into cells, and excreted from the kidney. Abnormalities of the parathyroid glands themselves will cause derangements of calcium homeostasis and several clinical disorders. PTH oversecretion due to parathyroid tumours, which affect 3 in 1000 of the population, is a major cause of hypercalcaemia which may be associated with kidney stones, osteoporosis, and peptic ulcers. PTH deficiency, which results in hypocalcaemia and occurs in 1 in 4000 live births, may be associated with epilepsy, tetany, cataracts, skeletal malformations, and abnormal dentition. This chapter will review the physiological and biochemical mechanisms underlying extracellular calcium homeostasis, the clinical features of hypercalcaemia and hypocalcaemia, the clinical disorders associated with abnormal calcium homeostasis and their management, and the genetic basis for disorders of calcium metabolism.
Crohn’s disease
Authors: Parkes Miles , Raine Tim 
Published: February 2020

Abstract
Crohn’s disease is a common form of chronic inflammatory bowel disease. Typically involving one or more of the terminal ileum, colon, and perineum, it causes patchy transmural inflammation characterized microscopically by granulomata. Common complications include fibrotic strictures, fistulas, and abscesses. The initiating trigger is unknown, but an unregulated mucosal immune response to commensal bacteria drives the chronic inflammation. Variants in several genes involved in innate immunity are strongly associated, and smoking also increases the risk. Crohn’s disease confers significant morbidity but low mortality. Treatment of acute inflammatory disease is usually with corticosteroids or (occasionally) therapeutic diets, the latter particularly in children. For steroid dependence, frequent relapse, or objective evidence of uncontrolled mucosal inflammation, immunosuppression is indicated with immunomodulator or biological therapy or a combination of the two. First-line immunomodulators are azathioprine or 6-mercaptopurine, with methotrexate used as second-line therapy. Antitumour necrosis factor-α (anti-TNFα) antibody therapy can induce rapid remission of resistant disease and has a key role in maintaining remission in such cases. Despite increased use of immunosuppressants, 70 to 80% of patients require surgery in the long term, most commonly for ileal stricturing. Timely, conservative surgery is the key, minimizing the length of small-bowel resected and using laparoscopic approaches where possible. For colonic disease requiring surgery, segmental colectomy or subtotal colectomy with ileorectal anastomosis are preferred, but significant rectal or perianal involvement may require proctocolectomy and ileostomy. Perianal Crohn’s disease is treated medically with antibiotics, azathioprine, and anti-TNF antibody therapy, and surgically with abscess drainage and placement of seton sutures through fistulas where possible. Some fistulas heal with intensive medical therapy. Others may warrant attempts at surgical repair if they produce unacceptable symptoms.
Ulcerative colitis
Authors: Sanderson Jeremy , Irving Peter 
Published: February 2020

Abstract
Ulcerative colitis is a chronic relapsing and remitting disease in which chronic inflammation affects the rectum and extends proximally to a variable extent. The precise aetiology remains unknown but involves an interplay between reduced diversity in the gut microbiota and a genetically dysregulated gut immune system and epithelial barrier.
Typical presentation of mild or moderate disease is with a gradual onset of symptoms including diarrhoea, rectal bleeding, and the passage of mucus. Severe disease is characterized by anorexia, nausea, weight loss, and severe diarrhoea, with the patient likely to look unwell with fever, tachycardia, and other signs of volume depletion, and the abdomen may be distended and tympanitic, with reduced bowel sounds and marked colonic tenderness. Diagnosis is usually made on the basis of exclusion of infective colitis by stool culture and the finding of typical diffuse inflammation in the rectum and above at sigmoidoscopy. Management requires rapid control of symptoms with induction therapy followed by maintenance of remission. Mild disease is typically treated with 5-aminosalicyclic acid delivered both orally and by enema, and moderate disease by 5-aminosalicyclic acid and steroids. Patients with severe disease require hospital admission, intravenous steroids, and daily review by both a physician and a surgeon experienced in the management of ulcerative colitis. Ciclosporin or infliximab are used as rescue therapies for steroid-resistant acute severe ulcerative colitis, but colectomy should not be delayed when this is required. Maintenance therapy with immunomodulators and biological therapies are both effective at maintaining remission, and several new biologicals are in clinical trials.
Gastrointestinal infections
Authors: O’Brien Sarah 
Published: February 2020

Abstract
Gastrointestinal infections, especially diarrhoea and vomiting, are responsible for substantial morbidity, mortality, and socioeconomic penalties worldwide. Poor sanitation, inadequate water supplies, and globalization of food production, processing, and retailing increase the risk of large epidemics of food- and waterborne outbreaks of gastrointestinal disease. Acute diarrhoea can be caused by a range of pathogens. Gastrointestinal pathogens usually cause three principal syndromes: acute watery diarrhoea, acute bloody diarrhoea (inflammatory diarrhoea or dysentery), and persistent diarrhoea. They can also cause systemic disease. Patients who do not have high fever (&gt;38.5°C), systemic illness, tenesmus, bloody diarrhoea, a prolonged course (&gt;2 weeks), or dehydration require neither investigation nor treatment. Investigation is required in patients with any of these features, with faecal specimens examined by culture (bacterial pathogens and some protozoa), microscopy (ova, cysts, and parasites), immunoassays (some protozoa and viruses), and molecular methods, usually polymerase chain reaction (PCR) or reverse transcriptase PCR (bacterial toxin genes and viruses). A specific laboratory diagnosis is useful epidemiologically and therapeutically. Oral rehydration therapy is the priority for patients with mild to moderate diarrhoea as long as vomiting is not a major feature. Antimicrobial therapy is not recommended or usually required for uncomplicated diarrhoea, but antibiotic treatment is beneficial for cholera, giardiasis, cyclosporiasis, shigellosis, symptomatic traveller’s diarrhoea, Clostridium difficile diarrhoea, and typhoid. Antimotility drugs are useful in controlling moderate to severe diarrhoea in adults but they are not generally recommended for infants and young children under the age of 4 years. Strict attention to food and water precautions and hand washing helps reduce the risk of gastrointestinal infections. Immunization has not yet proved successful for combating many gastrointestinal pathogens, with the notable exception of rotavirus.
Asthma
Authors: Nanzer-Kelly Alexandra , Cullinan Paul , Menzies-Gow Andrew 
Published: February 2020

Abstract
Asthma is a chronic inflammatory disease of the bronchial airways that is characterized pathologically by a desquamative eosinophilic bronchitis and clinically by reversible airway narrowing and increased airway responsiveness to non-specific provocative stimuli. The condition is common, frequently disabling, and can cause death. In the Western world it now affects more than 10% of children and more than 5% of adults, and in England and Wales it is the cause of more than 100,000 hospital admissions and is the certified cause of death of 1,000–1,500 people each year. The risk of developing asthma is increased in atopic individuals, and in asthmatics natural allergen exposure induces asthma and airway hyper-responsiveness. Viral infections, most commonly with rhinoviruses, cause 80–85% of exacerbations of asthma in children and 50–75% in adults.
Miscellaneous conditions presenting to the rheumatologist
Authors: Carter Stuart , Dunkley Lisa , Adebajo Ade 
Published: February 2020

Abstract
Musculoskeletal symptoms can occur in a variety of diseases, or as drug side effects. Presentations and conditions discussed in this section include: multisystem diseases (e.g. adult-onset Still’s disease, acute sarcoid arthritis, and amyloidosis);
paraneoplastic syndromes (e.g. hypertrophic pulmonary osteoarthropathy, remitting seronegative symmetrical synovitis with pitting oedema, and tumour-induced osteomalacia); skin manifestations of rheumatic disease (e.g. panniculitis, neutrophilic dermatoses, and multicentric reticulohistiocytosis); primary joint pathology and synovial disorders (e.g. pigmented vilonodular synovitis, synovial osteochondromatosis, Charcot joint); rheumatic manifestations of haematological disease (e.g. haemophilia, sickle cell disease, leukaemia, lymphoma, and polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin abnormalities); rheumatic manifestations of metabolic disease (e.g. hereditary haemochromatosis, Wilson’s disease); disorders of the spine and axial skeleton (e.g. Tietze’s syndrome, diffuse idiopathic skeletal hyperostosis, and alkaptonuria); drug-induced rheumatic syndromes (e.g. statin-induced myopathy, drug-induced tendinopathy, drug-induced lupus, and allopurinol hypersensitivity).
Malignant diseases of the urinary tract
Authors: Eisen Tim , Hamdy Freddie C. , Huddart Robert A. 
Published: February 2020

Abstract
Bladder cancer—the seventh commonest cancer in the United Kingdom and the fourth most common in men. Nonmuscle-invasive disease is usually treated by transurethral resection with postoperative intravesical chemotherapy with mitomycin or bacillus Calmette–Guérin. Local muscle-invasive disease in patients who are fit enough is usually treated with radical cystoprostatectomy and cisplatin-based chemotherapy. Metastatic disease is typically treated with cisplatin-based chemotherapy. Renal cell cancer—approximately 3% of the total cancer burden. For operable patients with no distant disease, the treatment of choice is nephron-sparing (if possible) or radical nephrectomy. Metastatic renal cancer can behave in a very variable manner. Palliative nephrectomy may be required for bleeding or pain. First-line systemic treatment is with antiangiogenic tyrosine kinase inhibitors targeting vascular endothelial growth factor receptor signalling. Prostate cancer—second most common cause of male cancer deaths in the Western world. Most cases are asymptomatic at presentation, being detected following measurement of serum prostate-specific antigen (PSA) or after digital rectal examination, although screening by measurement of PSA remains a contentious issue. Clinically localized prostate cancer is treated with active monitoring, radiotherapy, or minimally invasive surgery. Locally advanced disease is likely to progress and requires intervention, usually in the form of androgen deprivation therapy and radiotherapy. First-line treatment for metastatic prostate cancer is androgen deprivation therapy; second-line treatment may be with newer antiandrogens in combination with steroids and cytotoxics. Testicular cancer—affects predominantly young adult men in whom they are the most common malignant tumours. For most patients, initial management consists of an inguinal orchidectomy, with or without immediate adjuvant therapy. Standard treatment of metastatic germ cell tumours is with a combination of bleomycin, etoposide, and cisplatin.