Persius/hicric huggingface dataset:
Antibody dependent enhancement
Antibody Dependent Enhacement (ADE) occurs when antiviral antibodies enhance viral entry into host cells, leading to increased infectivity. The most common example of ADE in during dengue infection. There are four serotypes of dengue virus, serotype 1, 2, 3 and 4. ADE occurs when a patient down with previous dengue infection is infected with dengue again but with a different serotype. These patients have severe clinical outcome and high viremia compared to patients who are down with dengue infection but have not suffered dengue infection from different serotype previously.
There are a few possibilities to explain the phenomena, using dengue as an example:
1. Viral surface protein laced with antibodies against dengue of other serotype (e.g. serotype 
1) binds to dengue virus serotype 2. The binding is meant to neutralize the virus surface protein from attaching to the cell, but instead the antibody bound to virus also binds to the receptor of the cell, Fc-region antibody receptor. This brings virus to close proximity to virus-specific receptor, and the cell endocytose the virus through normal infection route. 
2. Dengue virus surface protein may be attached with antibodies of different serotype and classical pathway of the complementation system may be activated. The complement cascade system is instead used to bind C1q attached to virus surface protein via antibodies, which in turn binds C1q receptor found on cells, bringing the virus and the cell close enough for specific virus receptor to bind the virus and infection begin. 1
3. When antibody of dengue virus is present for a different serotype, the supposedly neutralizing antibodies is unable to neutralize the virus, but is nevetheless ingested into the cell as a sub-neutralized virus particle. These viruses are phagocytosed as antigen-antibody complexes targeted for degradation by macrophages. Upon ingestion the antibodies no longer even sub-neutralize the body due to denaturing condition at the step for acidification of phagosome before fusion with lysosome. The virus become active and begin its proliferation within the cell.
Immunoglobulin class switching
Immunoglobulin class switching (or isotype switching or Isotypic Commutation) is a biological mechanism that changes an antibody from one class to another, for example, from an isotype called IgM to an isotype called IgG. During this process, the constant region portion of the antibody heavy chain is changed, but the variable region of the heavy chain stays the same. Since the variable region does not change, class switching does not affect the antigens that are bound by the antibody. Instead, the antibody retains affinity for the same antigens, but can interact with different effector molecules.

# Mechanism
Class switching occurs after activation of a mature B cell via its membrane-bound antibody molecule (or B cell receptor) to generate the different classes of antibody, all with the same variable domains as the original antibody generated in the immature B cell during the process of V(D)J recombination, but possessing distinct constant domains in their heavy chains.
Naive mature B cells produce both IgM and IgD, which are the first two heavy chain segments in the immunoglobulin locus. After activation by antigen, these B cells proliferate and begin to produce high levels of these antibodies. If these activated B cells are also activated via their CD40 and IL-4 receptors (both modulated by T helper cells), they undergo antibody class switching to produce IgG, IgA or IgE antibodies. During class switching, the constant region of the immunoglobulin heavy chain changes but the variable regions, and therefore antigen specificity, stay the same.  This allows different daughter cells from the same activated B cell to produce antibodies of different isotypes or subtypes (e.g. IgG1, IgG2 etc.).
The order of the heavy chain exons are as follows:
-  - IgM
-  - IgD
- 3 - IgG3
- 1 - IgG1
- pseudogene similar to  gene that is not used
- 1 - IgA1
- 2 - IgG2
- 4 - IgG4
-  - IgE
- 2 - IgA2
Class switching occurs by a mechanism called class switch recombination (CSR)binding.  This process uses conserved nucleotide motifs, called switch (S) regions, found in DNA upstream from each of the antibody heavy chain constant region genes, except the -chain. DNA is nicked and broken at two selected S-regions by the activity of a series of enzymes, including Activation-Induced (Cytidine) Deaminase (AID), uracil DNA glycosylase and apyrimidic/apurinic (AP)-endonucleases. The intervening DNA between the S-regions is subsequently deleted from the chromosome, removing the unwanted  or  heavy chain constant region genes and possibly some of the ,  or  constant region genes. The free ends of the DNA are rejoined by a process called non-homologous end joining (NHEJ) to link the variable domain exon to the desired downstream constant domain exon of the immunoglobulin heavy chain. Class switching can occur more than once, but it can only switch to heavy chain segments that are downstream (in the immunoglobulin locus) from the previous heavy chain exon. With the exception of the  and  genes, only one antibody class is expressed by a B cell at any point in time.
Argininosuccinate synthetase 1
Argininosuccinate synthetase is an enzyme that in humans is encoded by the ASS1 gene.
The protein encoded by this gene catalyzes the penultimate step of the arginine biosynthetic pathway. There are approximately 10 to 14 copies of this gene including the pseudogenes scattered across the human genome, among which the one located on chromosome 9 appears to be the only functional gene for argininosuccinate synthetase.  Two transcript variants encoding the same protein have been found for this gene.

# Clinical significance
Mutations in the chromosome 9 copy of ASS cause citrullinemia.
40% to 90% of bladder cancers are deficient in argininosuccinate synthetase.
Asymmetrical tonic neck reflex
The asymmetrical tonic neck reflex (ATNR) is a primitive reflex found in newborn humans, but normally vanishes by the child's first birthday.
It is also known as the "fencing reflex" because of the characteristic position of the infant's arms and head, which resemble those of a classically trained fencer.  When the face is turned to one side, the arm and leg on the side to which the face is turned extend and the arm and leg on the opposite side bend.
The presence of the ATNR, as well as other primitive reflexes such as the tonic labyrinthine reflex (TLR), beyond the first months of life may indicate that the child has developmental delays, at which point the reflex is atypical or abnormal.  For example, in children with cerebral palsy, the reflexes may persist and even be more pronounced.  As abnormal reflexes, both the asymmetrical tonic neck reflex (ATNR) and the tonic labyrinthine reflex (TLR) can cause problems for the growing child.  The ATNR and TLR both hinder functional activities such as rolling, bringing the hands together, or even bringing the hands to the mouth.  Over time, both the ATNR and TLR can cause serious damage to the growing child's joints and bones.  The ATNR can cause the spine to curve (scoliosis).  Both the ATNR and TLR can cause the head of the thighbone to partially slip out (subluxation) or completely move out of the hip socket (dislocation).
Bietti's crystalline dystrophy
Bietti's crystalline dystrophy (BCD), also called Bietti's crystalline retinopathy, is a rare autosomal recessive eye disease named for Dr. G. B. Bietti.
BCD is a rare disease and appears to be more common in people with Asian ancestry.

# Presentation
The symptoms of BCD include: crystals in the cornea (the clear covering of the eye); yellow, shiny deposits on the retina; and progressive atrophy of the retina, choriocapillaries and choroid (the back layers of the eye). This tends to lead to progressive night blindness and visual field constriction.

# Genetics
It has been associated with CYP4V2.
Tetrahydrobiopterin deficiency
Tetrahydrobiopterin deficiency (also known as BH4 deficiency) is a rare disorder that increases the blood levels of phenylalanine. Phenylalanine is an amino acid obtained through the diet. It is found in all proteins and in some artificial sweeteners. If tetrahydrobiopterin deficiency is not treated, excess phenylalanine can build up to harmful levels in the body, causing mental retardation and other serious health problems.
High levels of phenylalanine are present from infancy in people with untreated tetrahydrobiopterin deficiency. The resulting signs and symptoms range from mild to severe. Mild complications may include temporary low muscle tone. Severe complications include mental retardation, movement disorders, difficulty swallowing, seizures, behavioral problems, progressive problems with development, and an inability to control body temperature.

# Epidemiology
This condition is very rare; approximately 450 cases have been reported worldwide. In most parts of the world, only 1 % to 2 % of all infants with high phenylalanine levels have this disorder. In China, about 30 % of newborns with elevated levels of phenylalanine have a deficiency of tetrahydrobiopterin.

# Related genes
Mutations in the GCH1, PCBD1, PTS and QDPR genes cause tetrahydrobiopterin deficiency.
Tetrahydrobiopterin is a compound that helps convert several amino acids, including phenylalanine, to other essential molecules in the body. It is also involved in the production of chemicals called neurotransmitters that transmit signals between nerve cells in the brain. Tetrahydrobiopterin deficiency can be caused by mutations in one of several genes, including GCH1, PCBD1, PTS, and QDPR. These genes make enzymes that are critical for producing and recycling tetrahydrobiopterin. If one of the enzymes fails to function correctly because of a gene mutation, little or no tetrahydrobiopterin is produced. As a result, phenylalanine from the diet builds up in the bloodstream and other tissues and can damage nerve cells in the brain. Tetrahydrobiopterin deficiency also disrupts the levels of certain neurotransmitters in the brain, which affects the function of the central nervous system.

# Genetics
This condition is inherited in an autosomal recessive pattern, which means two copies of a specific gene in each cell are altered in order for the individual to be afflicted. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

# Treatment
Treatment of BH4 deficiencies consists of BH4 supplementation (2-20 mg/kg per day) or diet to control blood phenylalanine concentration and replacement therapy with neurotransmitters precursors (L-dopa/CarbiDOPA and 5-hydroxytryptophan) and supplements of folinic acid in DHPR deficiency.
Bacterial Genetic Nomenclature
Standards for bacterial genetic nomenclature were proposed in 1966 by Demerec et al..  Each bacterial gene is denoted by a mnemonic of three lower case letters which indicate the pathway or process in which the gene-product is involved, followed by a capital letter signifying the actual gene. In some cases, the gene letter may be followed by an allele number. All letters and numbers are underlined or italicised.  For example, leuA is one of the genes of the leucine biosynthetic pathway, and leuA273 is a particular allele of this gene.
Where the actual protein coded by the gene is known then it may become part of the basis of the mnemonic, thus:
- rpoA encodes the -subunit of RNA polymerase
- rpoB encodes the -subunit of RNA polymerase
- polA encodes DNA polymerase I
- polC encodes DNA polymerase III
- rpsL encodes ribosomal protein, small S12
Some gene designations refer to a known general function:
- dna is involved in DNA replication

# Common Mnemonics

## Biosynthetic Genes
Loss of gene activity leads to a nutritional requirement (auxotrophy) not exhibited by the wildtype (prototrophy).
Amino Acids:
- ala: alanine
- arg: arginine
- asn: asparagine
Some pathways produce metabolites that are precursors of more than one pathway. Hence, loss of one of these enzymes will lead to a requirement for more than one amino acid. For example:
- ilv: isoleucine and valine
Nucleosides:
- gua: guanine
- pur: purines
- pyr: pyrimidine
- thy: thymine
Vitamins:
- bio: biotin
- nad: NAD
- pan: pantothenic acid

## Catabolic Genes
Loss of gene activity leads to loss of the ability to catabolise (use) the compound.
- ara: arabinose
- gal: galactose
- lac: lactose
- mal: maltose
- man: mannose
- mel: melibiose
- rha: rhamnose
- xyl: xylose

## Drug and Bacteriophage Resistance Genes
- azi: azide resistance
- bla: beta-lactam resistance
- cat: chloramphinicol resistance
- kan: kanamyacin resistance
- rif: rifampicin resistance
- tonA: phage T1 resistance

## Nonsense Suppressor Mutations
- sup: suppressor (for instance, supF suppresses amber mutations)

# Mutant Nomenclature
If the gene in question is the wildtype a superscript '+' sign is used:
- leuA+
If a gene is mutant, it is signified by a superscript '-':
- leuA-
By convention, if neither is used, it is considered to be mutant.
There are additional superscripts and subscripts which provide more information about the mutation:
- ts: temperature sensitive (leuAts)
- cs: cold sensitive (leuAcs)
- am: amber mutation (leuAam)
- um: umber (opal) mutation (leuAum)
- oc: ochre mutation (leuAoc)
- R: resistant (rifR)
Other modifiers:
- : deletion ( leuA)
- :: : insertion (pyrC103::Tn10)

# Phenotype Nomenclature
When referring to the genotype (the gene) the mnemonics are not capitalised. When referring to the phenotype (the gene product), the mnemonic is capitalised and not italicized (e.g. DnaA - the protein produced by the dnaA gene).
Benign lymphoepithelial lesion

# Overview
Benign lymphoepithelial lesion is a type of benign enlargement of the parotid and/or lacrimal glands.  This pathologic state is sometimes, but not always, associated with Sjogren's syndrome.
Historically, bilateral parotid and lacrimal gland enlargement was characterized by the term Mikulicz's disease if the enlargement appeared apart from other diseases.  If it was secondary to another disease, such as tuberculosis, sarcoidosis, lymphoma, and Sjogren's syndrome, the term used was Mikulicz's syndrome.  Both names derive from Jan Mikulicz-Radecki, the Polish surgeon best known for describing these conditions.  Today, the terms "Mikulicz's disease" and "Mikulicz's syndrome" are viewed as ambiguous and outdated.

# Locations
Occurring in 80% of cases, the gland most likely to be affected is the parotid gland.  Lacrimal glands are also affected.

# Characteristic
Benign lymphoepithelial lesion is most likely to occur in adults around 50 years of age.  There is a predilection for gender with 60% - 80% being female. The gland affected has a diffuse swelling. The swelling can be asymptomatic, but mild pain can also be associated.
Most cases of benign lymphoepithelial lesions appear in conjunction with Sjogren's syndrome. When Sjogren's syndrome is present, the swelling is usually bilateral. Otherwise, the affected glands are usually only on one side of the body.
In most cases, a biopsy is needed to distinguish benign lymphoepithelial lesions from sialadenosis (sialosis).

# Histology
There is a marked lymphoplasmacytic infiltration. Lymphoid follicles surround solid epithelial nests, giving rise to the 'epimyoepithelial islands', that are mainly composed of ductal cells with occasional myoepithelial cells. Excess hyaline basement membrane material is deposited between cells, and there is also acinar atrophy and destruction.

# Treatment
Treatment usually consists of surgical removal of the affected gland. Prognosis is usually good,  however occasionally this condition may evolve into lymphoma, or represent occult lymphoma from the outset.
Benign paediatric heart murmur
A benign paediatric heart murmur, also innocent heart murmur or innocent murmur, is an inconsequential sound that originate from the heart and/or cardiovascular system and is heard on cardiac auscultation.  By definition, an innocent murmur is not significant in the long-term health of an individual that has it.

# Murmurs - innocent versus pathological
Characteristics of innocent murmurs are:
- Less than 3/6 in intensity, soft
- Often position-dependent (supine versus upright)
- Otherwise healthy individual, no concerns about growth
- Continuous (throughout cardiac cycle) or systolic (diastolic-only sounds are always pathologic)
- Normal S2 splitting (S2 splitting with inspiration)
- No palpable thrill (vibration of the chest due to abnormal heart movement/blood flow)

# Prognosis
Innocent murmurs are inconsequential and usually disappear as the child grows. ECG and Chest XRAY are normal.

# Types, description and DDx
LLSB = lower left sternal border
Simpson-Golabi-Behmel syndrome
Simpson-Golabi-Behmel syndrome (SGBS), also called Bulldog syndrome or Sara Agers Syndrome, is a rare congenital genetic syndrome with widely variable expression, causing craniofacial and other abnormalities.
It is inherited in an X-linked recessive fashion, meaning that generally only males are affected, but females are carriers.

# Presentation
Affected individuals typically have pre- or postnatal overgrowth leading to coarse ("bulldog-like") faces with protruding jaw and tongue, widened nasal bridge, and upturned nasal tip.  They often are quite tall. Intelligence is usually normal, although mental retardation does occur.  They often have abnormalities of the extremities, such as broad, short hands and feet, occasionally with polydactyly.  Other  abnormalities may include pectus excavatum, ventricular septal defect (or other congenital heart defects), Meckel diverticulum, intestinal malrotation, and congenital diaphragmatic hernia.
People with this syndrome may have an increased risk of tumors, such as neuroblastoma or Wilms tumor.
SGBS is somewhat similar to another overgrowth syndrome called Beckwith-Wiedemann syndrome, probably because both syndromes affect insulin-like growth factor 2 (IGF2).
CATAPRES clinical pharmacology

# Clinical Pharmacology
Clonidine stimulates alpha-adrenoreceptors in the brain stem. This action results in reduced sympathetic outflow from the central nervous system and in decreases in peripheral resistance, renal vascular resistance, heart rate, and blood pressure. CATAPRES tablets act relatively rapidly. The patients blood pressure declines within 30 to 60 minutes after an oral dose, the maximum decrease occurring within 2 to 4 hours. Renal blood flow and glomerular filtration rate remain essentially unchanged. Normal postural reflexes are intact; therefore, orthostatic symptoms are mild and infrequent.
Acute studies with clonidine hydrochloride in humans have demonstrated a moderate reduction (15% to 20%) of cardiac output in the supine position with no change in the peripheral resistance: at a 45 tilt there is a smaller reduction in cardiac output and a decrease of peripheral resistance. During long term therapy, cardiac output tends to return to control values, while peripheral resistance remains decreased. Slowing of the pulse rate has been observed in most patients given clonidine, but the drug does not alter normal hemodynamic response to exercise.
Tolerance to the antihypertensive effect may develop in some patients, necessitating a reevaluation of therapy.
Other studies in patients have provided evidence of a reduction in plasma renin activity and in the excretion of aldosterone and catecholamines. The exact relationship of these pharmacologic actions to the antihypertensive effect of clonidine has not been fully elucidated.
Clonidine acutely stimulates growth hormone release in both children and adults, but does not produce a chronic elevation of growth hormone with long-term use.

### Pharmacokinetics
The pharmacokinetics of clonidine is dose-proportional in the range of 100 to 600 g. The absolute bioavailability of clonidine on oral administration is 70% to 80%. Peak plasma clonidine levels are attained in approximately 1 to 3 hours.
Following intravenous administration, clonidine displays biphasic disposition with a distribution half-life of about 20 minutes and an elimination half-life ranging from 12 to 16 hours. The half-life increases up to 41 hours in patients with severe impairment of renal function. Clonidine crosses the placental barrier. It has been shown to cross the blood-brain barrier in rats.
Following oral administration about 40% to 60% of the absorbed dose is recovered in the urine as unchanged drug in 24 hours. About 50% of the absorbed dose is metabolized in the liver. Neither food nor the race of the patient influences the pharmacokinetics of clonidine.
The antihypertensive effect is reached at plasma concentrations between about 0.2 and 2.0 ng/mL in patients with normal excretory function. A further rise in the plasma levels will not enhance the antihypertensive effect.
Cardiac allograft vasculopathy
Synonyms and keywords: CAV, cardiac transplant vasculopathy, heart transplant vasculopathy, HTx vasculopathy, transplant coronary artery disease, transplant CAD, graft coronary artery disease, graft CAD, heart transplant coronary artery disease, heart transplant CAD

# Overview

# Historical Perspective

# Pathophysiology

# Differentiating Cardiac allograft vasculopathy from other Diseases

# Epidemiology and Demographics

# Risk Factors

# Screening

# Natural History, Complications and Prognosis

# Diagnosis
History and Symptoms | Physical Examination | Laboratory Findings | Electrogardiogram | Chest X Ray | Coronary Angiography | Intravascular Ultrasound | Optical Coherence Tomography | CT | MRI | Echocardiography | Other Imaging Findings | Other Diagnostic Studies

# Treatment
Medical Therapy | Surgery | Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

# Case Studies
Case #1
CME Category::Cardiology
Cyclic guanosine monophosphate
Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP, most notably by activating intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell surface.

# Synthesis
cGMP synthesis is catalyzed by guanylate cyclase (GC), which converts GTP to cGMP. Membrane-bound GC is activated by peptide hormones such as the atrial natriuretic factor, while soluble GC is typically activated by nitric oxide to stimulate cGMP synthesis.

# Effects
cGMP is a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. It also relaxes smooth muscle tissues.  In blood vessels, relaxation of vascular smooth muscles lead to vasodilation and increased blood flow.
cGMP is a secondary messenger in phototransduction in the eye. In the photoreceptors of the mammalian eye, the presence of light activates phosphodiesterase, which degrades cGMP. The sodium ion channels in photoreceptors are cGMP-gated, so degradation of cGMP causes sodium channels to close, which leads to the hyperpolarization of the photoreceptor's plasma membrane and ultimately to visual information being sent to the brain.

# Degradation
Cyclic nucleotide phosphodiesterases (PDE 1-6) degrade cGMP by hydrolyzing cGMP into 5'-GMP.
Phosphodiesterase inhibitors prevent the degradation of cGMP, thereby enhancing and/or prolonging its effects. For example, Sildenafil (Viagra) enhances the vasodilatory effects of cGMP within the corpus cavernosum by inhibiting PDE 5 (or PDE V). This is used as a treatment for erectile dysfunction. However, the drug can inhibit PDE6 in retina with less affinity than PDE5, so it may lead blue vision.

# Protein kinase activation
cGMP is involved in the regulation of some protein-dependent kinases. For example, PKG (protein kinase G) is a dimer consisting of one catalytic and one regulatory unit, with the regulatory units blocking the active sites of the catalytic units.
cGMP binds to sites on the regulatory units of PKG and activates the catalytic units, enabling them to phosphorylate their substrates. Unlike with the activation of some other protein kinases, notably PKA, the PKG is activated but the catalytic and regulatory units do not disassociate.