Persius/hicric huggingface dataset:
Costello syndrome

# Overview
Costello syndrome is a genetic disorder that affects many parts of the body. This condition is characterized by delayed development and mental retardation, distinctive facial features, loose folds of extra skin (especially on the hands and feet), and unusually flexible joints. Heart abnormalities are common, including a very fast heartbeat (tachycardia), structural heart defects, and overgrowth of the heart muscle (hypertrophic cardiomyopathy). Infants with Costello syndrome may be large at birth, but have difficulty feeding and grow more slowly than other children. Later in life, people with this condition have relatively short stature and many lack growth hormone.
Beginning in early childhood, people with Costello syndrome have an increased risk of developing certain cancerous and noncancerous tumors. Small growths called papillomas are the most common noncancerous tumors seen with this condition. They usually develop around the nose and mouth or near the anus. The most frequent cancerous tumor associated with Costello syndrome is a soft tissue tumor called a rhabdomyosarcoma. Other cancers also have been reported in children and adolescents with this disorder, including a tumor that arises in developing nerve cells (neuroblastoma) and a form of bladder cancer (transitional cell carcinoma).

# Genetics
Mutations in the HRAS gene cause Costello syndrome. The HRAS gene provides instructions for making a protein that helps control cell growth and division. Mutations that cause Costello syndrome lead to the production of an HRAS protein that is permanently active. Instead of triggering cell growth in response to particular signals from outside the cell, the overactive protein directs cells to grow and divide constantly. This unchecked cell division may predispose to the development of benign and malignant tumors. It remains unclear how mutations in the HRAS gene cause the other features of Costello syndrome, but many of the signs and symptoms may result from cell overgrowth and abnormal cell division.
Costello syndrome is inherited in an autosomal dominant manner, which means one copy of the altered gene is sufficient to cause the disorder. Almost all cases have resulted from new mutations, and occur in people with no history of the disorder in their family. This condition is rare; 200 to 300 (20/04/2007)cases have been reported worldwide.
A support group for families affected by Costello syndrome was founded in the UK in 1997. Although based in the UK, the support group runs a web site, and Listserve for families, and has formed a strong international community. The UK support group is a registered charity.
In 2001 a similar not-for-profit organization for Costello syndrome was founded in the USA. 
The two organizations work hand in hand, providing a high level of support and information with the aim of gaining a much better understanding of this rare disorder.
The support group has a membership of 160 families world wide (05/03/2007)
Tietze's syndrome
Synonyms and keywords: Costochondritis

# Overview
Tietze's syndrome, also known as costochondritis, is a benign inflammation of one or more of the costal cartilages.  It was first described in 1921 by the German surgeon Alexander Tietze (1864-1927). 
Tietze's syndrome and costochondritis were initially described as separate conditions, the sole difference being that in Tietze's syndrome there is swelling of the costal cartilages. It is now recognized that the presence or absence of swelling is only an indicator of the severity of the condition. It was at one time thought to be associated with, or caused by, a viral infection acquired during surgery, but this is now known not to be the case. Most sufferers have not had recent surgery.
It should not be confused with Tietz syndrome.

# Causes
While the true causes of Tietze's Syndrome are not well understood, it often results from a physical strain or minor injury, such as repeated coughing, vomiting or impacts to the chest. It has even been known to occur after hearty bouts of laughter. It can occur by over exerting
-r by an injury in the chest .

# Differentiating Tietze's syndrome from other Diseases
Although patients will often mistake the pain of Tietze's Syndrome for a myocardial infarction (heart attack), the syndrome does not progress to cause harm to any organs.
Doctors often reassure patients that their symptoms are not associated with a heart attack, although they may need to treat the pain, which in some cases can be severe enough to cause significant but temporary disability to the patient.
There is pain and discomfort in the chest wall of the patient. The pain is generally at night and in the morning. The pain subsides in five to six hours. The patient must not move or exert during pain. The patient should lie down and lightly massage the affected area.

# Diagnosis
The primary presentation of the syndrome is significant, acute pain in the chest, along with tenderness and some swelling of the cartilages affected, which is commonly palpable on examination. Although many times it can be extremely painful, to the point of being debilitating, Tietze's Syndrome is considered to be a benign condition that generally resolves in 6-8 weeks.
Perceived pain is often exacerbated with respiration.
Costochondritis symptoms are similar to the chest pain associated with a heart attack.
If the pain does not completely cease within two months, the patient must consult a doctor.
Cotton wool spots

# Overview
Cotton wool spots are an abnormal finding on fundoscopic exam of the retina. They appear as puffy white patches on the retina.

# Pathophysiology
They are caused by damage to nerve fibers. The nerve fibers are damaged by swelling in the surface layer of the retina. The cause of this swelling is due to the reduced axonal transport (and hence backlog of intracellular products) within the nerves because of the ischaemia.

# Causes

## Common Causes
- Diabetes
- Hypertension

## Rare Causes
- HIV
- Pancreatitis (Purtscher retinopathy)

# Treatment
Treatmen of the underlying disease is the mainstay of therapy. In diabetes, cotton wool spots are one of the hallmarks of pre-proliferative retinopathy.
Coupling reaction
A coupling reaction or oxidative coupling in organic chemistry is a  catch-all for a range of reactions in Organometallic chemistry where two hydrocarbon radicals are coupled with the aid of a metal containing catalyst.
Coupling reactions should be divided into two main classes, there are the cross couplings in which two different molecules react to form one new molecule. For example the nickel chloride catalyzed reaction of an aryl magnesium halide with an aryl halide to form a biaryl.
An example of the other type of coupling (homocoupling) would be a Ullmann reaction, this is the reaction of  copper metal with two molecules of an aryl halide to form a biaryl. The Ullmann reaction often requires very high temperatures, and has partly been replaced in synthetic chemistry by palladium based reactions.
Many coupling reactions involve phenols. BINOL is the C-C coupling reaction product of 2-naphthol with copper(II) chloride and 2,6-xylenol dimerises as well with iodosobenzene diacetate.
A common metal in this type of chemistry is palladium often added in the form of tetrakis(triphenylphosphine)palladium(0). This is an air sensitive compound which is very good for coupling unsaturated halogen compounds with organometallics such as tributyltin hydride.
While many coupling reactions involve reagents that are extremely susceptible to presence of water or oxygen, it is unreasonable to assume that all coupling reactions need to be performed with strict exclusion of water. It is possible to perform palladium based coupling reactions in aqueous solutions using the water soluble sulfonated phosphines made by the reaction of triphenyl phosphine with sulfuric acid. In general the oxygen in the air is more able to disrupt coupling reactions, this is because many of these reactions occur via unsaturated metal complexes which do not have 18 valence electrons. For example in nickel and palladium cross couplings a zerovalent complex with two vacant sites (or labile ligands) reacts with the carbon halogen bond to form a metal halogen and a metal carbon bond. Such a zerovalent complex with labile ligands or empty coordination sites is normally very reactive towards oxygen.

# Coupling types
Coupling reactions include (not exhaustive):

# Miscellaneous reactions
In one study an unusual coupling reaction was described in which an organomolybdenum compound, 2
not only sat on a shelf for 30 years without any sign of degradation but also decomposed in water to generate 2-butyne which is the coupling adduct of its two ethylidyne ligands. This according to the researchers opens another way for aqueous organometallic chemistry.
One method for palladium-catalyzed cross coupling reactions of aryl halides with fluorinated arenes, involves DMA. It is unusual in that it involves C-H functionalisation at an electron deficient arene.
Courvoisier's law
Courvoisier's law (or Courvoisier syndrome, or Courvoisier's sign) states that in the presence of a palpable gall bladder, jaundice is unlikely to be caused by gallstones. This is because gallstones are formed over a longer period of time, and this results in a shrunken, fibrotic gall bladder which does not distend easily. Therefore the gall bladder is more often enlarged in pathologies that cause obstruction of the biliary tree over a shorter period of time such as pancreatic malignancy.
It is named for Ludwig Georg Courvoisier.
(Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, California)
- Cholangiocarcinoma has caused patient's gall    bladder to become markedly dilated, and therefore, easily palpable (A). Note skin is also jaundiced due to biliary tract obstruction.
- CT sagital image demonstrates dilated  gall bladder (B), dilated common bile duct (C), and dilated intrahepatic ducts    (D). Courvoisier described the same findings in patients with pancreatic cancer.
Coxiella burnetii

# Overview
Coxiella burnetii is an obligate intracellular bacterial pathogen, and is the causative agent of Q fever. The genus Coxiella is morphologically similar to Rickettsia, but with a variety of genetic and physiological differences. C. burnetii is a small Gram-negative bacterium that is highly resistant to environmental stresses such as high temperature, osmotic pressure, and ultraviolet light. These characteristics are attributed to a small cell variant form of the organism that is part of a biphasic developmental cycle, including a more metabolically and replicatively active large cell variant form. It can survive standard disinfectants, and is resistant to many other environmental changes like those presented in the phagolysosome.

# Pathogenesis
The ID50 (the dose needed to infect 50% of experimental subjects) is one via inhalation; i.e., inhalation of one organism will yield disease in 50% of the population. This is an extremely low infectious dose (only 1-10 organisms required), making C. burnetii one of the most infectious known organisms. Disease occurs in two stages: an acute stage that presents with headaches, chills, and respiratory symptoms, and an insidious chronic stage.
While most infections clear up spontaneously, treatment with tetracycline or doxycycline appears to reduce the symptomatic duration and reduce the likelihood of chronic infection. A combination of erythromycin and rifampin is highly effective in curing the disease, and vaccination with Q-VAX vaccine (CSL) is effective for prevention of it.  
The bacteria use a Type IVB secretion system known as Icm/Dot to inject effector proteins called Ank proteins into the host. These effectors increase the bacteria's ability to survive inside the host cell. In Legionella pneumophila, which uses the same secretion system and also injects Ank proteins, survival is enhanced because these Ank proteins interfere with fusion of the bacteria-containing vacuole with the host's degradation endosomes.

# Genomics
There are currently at least 5 completely sequenced genomes of Coxiella burnetti  which contain about 2.1 Mbp of DNA each and encode around 2,100 open reading frames. 746 (or about 35%) of these genes have no known function.
Crown-rump length

# Overview
Crown Rump Length is usually abbreviated as CRL. It is the measurement of the length of the unborn human fetus from the top of the head (crown) to the bottom of the buttocks (rump).

# Measuring
The fetus floats in the amniotic fluid inside the uterus of the mother usually in a curved posture resembling the letter C. The measurement can actually vary slightly if the fetus is temporarily stretching (straightening) its body. The measurement needs to be in the natural state with an unstretched body which is actually C shaped. The measurement of CRL is useful in determining the gestational age (menstrual age starting from the first day of the last menstrual period) and thus the expected date of delivery (EDD). Different babies do grow at different rates and thus the gestational age is an approximation. Early in pregnancy it is accurate within +/- 4 days but later in pregnancy due to different growth rates, the accuracy is less. In that situation, other parameters can be used in addition to CRL.
Gestational age is not the same as fetal age. It takes about 14 days from the first day of the last menstrual period for conception to take place and thus for the conceptus to form. The age from this point in time (conception) is called the fetal age and is thus 2 weeks shorter than the gestational age. Thus a 6 week gestational age would be a 4 week fetal age. Some authorities however casually interchange these terms and the reader is advised to be cautious. An average gestational period (duration of pregnancy from the first day of the last menstrual period up to delivery) is 280 days. Thus if all months were of 31 days, it would be 9 months and 1 day.

## Typical measurements
Following formula is an approximation:
Gestational age (weeks) = crown-rump length (cm) + 6.5
Cyclic ADP-ribose
Cyclic ADP Ribose, popularly known as cADPR, is a cyclic adenine nucleotide (like cAMP) with two phosphate groups present on 5' OH of the adenosine (like ADP), further connected to another ribose at the 5' position, which, in turn, closes the cycle by glycosidic bonding to the Nitrogen1 of the same Adenine base (whose position 9 has the glycosidic bond to the other ribose). It is produced from nicotinamide adenine dinucleotide (NAD+) by ADP-ribosyl cyclases (EC 3.2.2.5) as part of a second messenger system.

# Function
cADPR is a cellular messanger for calcium signaling. It is the physiological allosteric modulator of the ryanodine receptor (RyR), which stimulates calcium-induced calcium release (CICR) at lower cytosolic concentrations. RyR activation with high concentration of caffeine is partly due to caffeine's mimicking the binding of cADPRs to RyRs. Whether the action is by direct binding to RyR or indirect (through binding with FKBP12.6) is debated. Some reports suggest that cADPR binding makes FKBP12.6, which normally binds RyR2, to fall off the RYR2.

# Metabolism
cADPR is synthesized from NAD+ by the bifunctional ectoenzymes of the CD38 family (also includes ADP ribosyl cyclase of Aplysia and GPI anchored CD157). The same enzymes are also capable of hydrolyzing it to ADPR. Catalysis proceeds via a covalently-bound intermediate. The hydrolysis reaction is inhibited by ATP, and the cyclic form of APDR may accumulate.
Library (biology)

# Overview
In molecular biology, a library is a collection of molecules in a stable form that represents some aspect of an organism. Two common types of libraries are  cDNA libraries (formed from Complementary DNA) and genomic libraries. The nucleotide sequences of interest are preserved as inserts to a plasmid or the genome of a bacteriophage that has been used to infect bacterial cells.
A cDNA library represents all of the mRNA present in a particular tissue, which has been converted back to a DNA template by the use of the enzyme reverse transcriptase. It represents the genes that are transcribed in particular tissues under particular physiological, developmental, or environmental conditions. cDNA libraries are useful in reverse genetics, but should not be confused with a genomic library, as it does not represent the entire genome, only a very small (less than 1%) portion which is being transcribed.
A genomic library is a set of clones, packaged in the same vector, that together represents all regions of the genome of the organism in question.  The number of clones that constitute a genomic library depends on (1) the size of the genome in question and (2) the insert size tolerated by the particular cloning vector system.
Usually a cDNA library is created when reproducing eukaryotic genomic material, whereas genomic libraries are often created when working with genomic target material from bacteria and viruses.
DNA polymerase mu
DNA polymerase mu is a polymerase enzyme found in eukaryotes. In humans, this protein is encoded by the POLM gene.

# Function
Pol  is a member of the X family of DNA polymerases.  It participates in resynthesis of damaged or missing nucleotides during the non-homologous end joining (NHEJ) pathway of DNA repair.  Pol  interacts with Ku and DNA ligase IV, which also participate in NHEJ.  It is structurally and functionally related to pol , and, like pol , pol  has a BRCT domain that is thought to mediate interactions with other DNA repair proteins.  Unlike pol , however, pol  has the unique ability to add a base to a blunt end that is templated by the overhang on the opposite end of the double-strand break.  Pol  is also closely related to terminal deoxynucleotidyl transferase (TdT), a specialized DNA polymerase that adds random nucleotides to DNA ends during V(D)J recombination, the process by which B-cell and T-cell receptor diversity is generated in the vertebrate immune system.  Like TdT, pol  participates in V(D)J recombination, but only during heavy chain rearrangements.  This is distinct from pol , which is involved in light chain rearrangements.

# POLM mutant mice
In polymerase mu mutant mice, hematopoietic cell development is defective in several peripheral and bone marrow cell populations with about a 40% decrease in bone marrow cell number that includes several hematopoietic lineages.  Expansion potential of hematopoietic progenitor cells is also reduced.  These characteristics correlate with reduced ability to repair double-strand breaks in hematopoietic tissue.  Whole body gamma irradiation of polymerase mu mutant mice indicates that polymerase mu also has a role in double-strand break repair in other tissues unrelated to hematopoietic tissue.  Thus polymerase mu has a significant role in maintaining genetic stability in hematopoietic and non-hematopoietic tissue.
Deoxyribonuclease

# Overview
A deoxyribonuclease (DNase, for short) is any enzyme that catalyzes the hydrolytic cleavage of phosphodiester linkages in the DNA backbone.  Deoxyribonucleases are thus one type of nuclease.  A wide variety of deoxyribonucleases are known, which differ in their substrate specificities, chemical mechanisms, and biological functions.

# Modes of action
Some DNases cleave only residues at the ends of DNA molecules (exodeoxyribonucleases, a type of exonuclease).  Others cleave anywhere along the chain (endodeoxyribonucleases, a subset of endonucleases).
Some are fairly indiscriminate about the DNA sequence at which they cut, while others, including restriction enzymes, are very sequence-specific.
Some cleave only double-stranded DNA, others are specific for single-stranded molecules, and still others are active toward both.

# Types of deoxyribonucleases
The two main types of DNase found in metazoans are known as deoxyribonuclease I and deoxyribonuclease II.
Other types of DNase include Micrococcal nuclease.

# Assay of deoxyribonucleases
DNA absorbs UV light with a wavelength of maximal absorbance near 260 nm.  This absorption is due to the pi electrons in the aromatic bases of the DNA.  In dsDNA, or even regions of RNA where double stranded structure occurs, the bases are stacked parallel to each other and the overlap of the base molecular orbitals leads to a decrease in absorbance of UV light.  This phenomenon is called the hyperchromic effect.  When DNAse liberates nucleotides from dsDNA, the bases are no longer stacked like they are in dsDNA, so that orbital overlap is minimized and UV absorbance increases.  This increase in absorbance underlies the basis of Kunitz unit of DNAse activity.  One Kunitz unit is defined as the amount of enzyme that causes an increase in absorbance at 260 nm of 0.001 per mL when acting upon highly polymerized DNA at 25 C and pH 5.0 under specified conditions.  A standard enzyme preparation should be run in parallel with an unknown because standardization of DNA preparations and their degree of polymerization in solution is not possible.
Pigmented lesions

# Overview
Pigmented lesions are common and in many cases benign. Though many are benign, it is important for the physician to rule out melignancy to ensure it is not dangerous. They will do this with a biopsy to determine the diagnosis.

# Classification
The three most common types are:
- Nevi
- Seborrheic keratosis
- Dermatofibromas

# Causes

## Causes in Alphabetical Order
- Benign mole
- Blue Nevus
- Cafe au lait macule
- Dermatofibroma
- Dysplastic nevus
- Freckle
- Malignant Melanoma
- Seborrheic Keratosis
- Solar lentigo

# Diagnosis

## History and Symptoms
- Note: changes in skin appearance, lesion size, lesion length, any bleeding or irritation

## Other Diagnostic Studies

### Biopsy
- Shave biopsy: tests for actinic keratosis & seborrheic keratoses
- Deep scoop shave biopsy, excisional biopsy, punch biopsy: tests for dysplastic nevus and melanoma

# Treatment

## Medical Therapy
- Solar lentigines & Freckles: reassurance, lasers or pulse light

## Surgery and Device Based Therapy
- Keratoses: topical cryotherapy

## Primary Prevention
- Sunscreen
- Annual full skin exams
Rheumatoid factor
Rheumatoid factor (RF or RhF) is a blood test performed in patients with suspected rheumatoid arthritis (RA).
It is an antibody against the Fc portion of IgG, which is itself an antibody, IgM or IgA type; RF and IgG form immune complexes, which are part of the disease process of various rheumatological diseases. Rheumatoid factor can be either Type 2 (monoclonal IgM to polyclonal IgG) or 3 (polyclonal IgM to polyclonal IgG) cryoglobulin.
These factors are antibodies in the serum of people who suffer from rheumatoid arthritis. Antigenic determinants or immunoglobins.
- Positive in persons with symptoms

# Indications
RF is often determined in patients suspected in any form of arthritis. It has relatively little use there, as positive results can be due to other causes, and negative results do not rule out disease. But, in combination with signs and symptoms, it can be diagnostic and prognostic. It is part of the disease criteria of RA.

# Interpretation
High levels RF (generally above 20 IU/mL, 1:40 or over the 95th percentile there is some variation among labs) are indicative of rheumatoid arthritis (present in 80%) and Sjogren's syndrome  (present in almost 100%) .
The higher the levels of RF the higher the possibility of a more destructive articular disease.
There is a high rate of false positives due to other causes. These are:

# Differential Diagnosis
- Anthracosis
- Any chronic viral infection
- Asbestos
- Asthma
- Bacterial endocarditis
- Behcet's Syndrome
- Bronchitis
- Chronic hepatitis
- Cirrhosis
- Cryoglobulinemia
- Dermatomyositis
- Hepatitis
- Juvenile Rheumatoid Arthritis
- Leukemia
- Mixed connective tissue disease
- Infectious mononucleosis
- Myocardial Infarction
- Neoplasm
- Osteomyelitis
- Polymyositis
- Sarcoidosis
- Sclederoma
- Sjogren's Syndrome
- Syphillis
- Systemic Lupus Erythmatosus (SLE)
- Tuberculosis