Persius/hicric huggingface dataset:
DHTKD1
Dehydrogenase E1 and transketolase domain containing 1 is a protein that in humans is encoded by the DHTKD1 gene. This gene encodes a component of a mitochondrial 2-oxoglutarate-dehydrogenase-complex-like protein involved in the degradation pathways of several amino acids, including lysine. Mutations in this gene are associated with 2-aminoadipic 2-oxoadipic aciduria and Charcot-Marie-Tooth Disease Type 2Q.

# Structure
The DHTKD1 gene encodes a protein that has 919 amino acids, and is one of two isoforms within the 2-oxoglutarate-dehydrogenase complex.

# Function
DHTKD1 is part of an OGDHc-like supercomplex that is responsible for a crucial step in the degradation pathways of L-lysine, L-hydroxylysine, and L-tryptophan. Specifically, this enzyme catalyzes the decarboxylation of 2-oxoadipate to glutaryl-CoA.
There is a strong correlation between DHTKD1 expression levels and ATP production, which signifies that DHTKD1 plays a critical role in energy production in mitochondria. Moreover, suppression of DHTKD1 results in decreased levels of biogenesis and increased levels of reactive oxygen species (ROS) within the mitochondria. Globally, this impairs cell growth and enhances cell apoptosis.

# Clinical significance
Mutations in the DHTKD1 gene are associated with alpha-aminoadipic and alpha-ketoadipic aciduria, an autosomal recessive inborn error of lysine, hydroxylysine, and tryptophan degradation. Only a handful of mutations have been observed in patients, including three missense mutations, two nonsense mutations, two splice donor mutations, one duplication, and one deletion and insertion. Two missense mutations are the most common cause of the deficiency. The clinical presentation of this disease in inconsistent.
Mutations in this gene could also cause neurological abnormalities. Indeed, one form of Charcot-Marie-Tooth (CMT) disease has been associated with DHTKD1, although the disease encompasses a wide spectrum of clinical neuropathies. Specifically, a hyterozygous nonsense mutation within the gene leads to decreased levels of DHTKD1 mRNA and proteins, and impaired ATP generation. This implicates this mutation as a causative agent for CMT-2 Disease.
DIAPH1
Protein diaphanous homolog 1 is a protein that in humans is encoded by the DIAPH1 gene.

# Function
This gene is a homolog of the Drosophila diaphanous gene and belongs to the protein family of the formins, characterized by the formin homology 2 (FH2) domain. It has been linked to autosomal dominant, fully penetrant, nonsyndromic low-frequency progressive sensorineural hearing loss. Actin polymerization involves proteins known to interact with diaphanous protein in Drosophila and mouse. It has therefore been speculated that this gene may have a role in the regulation of actin polymerization in hair cells of the inner ear. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

# Interactions
DIAPH1 has been shown to interact with RHOA.

# Clinical significance
Mutations in this gene have been associated with macrothrombocytopenia and hearing loss,  microcephaly, blindness, and early onset seizures
Its actions on platelet formation appear to occur at the level of the megakaryocyte where it is involved in cytoskeleton formation.
DLGAP1
Disks large-associated protein 1 (DAP-1), also known as guanylate kinase-associated protein (GKAP), is a protein that in humans is encoded by the DLGAP1 gene. DAP-1 is known to be highly enriched in synaptosomal preparations of the brain, and present in the post-synaptic density.

# Function
This gene encodes the protein called guanylate kinase-associated protein (GKAP).  GKAP binds to the SHANK and PSD-95 proteins, facilitating the assembly of the post-synaptic density of neurons. Dlgap1 has five 14-amino-acid repeats and three Pro-rich portions.

# Interactions
DLGAP1 has been shown to interact with:
- DLG1
- DLG4
- DYNLL1
- DYNLL2
- SHANK2
The interaction with PSD95 and S-SCAM is mediated by the GUK domain and it has been hypothesized that this might mean it can also interact with other GUK containing proteins.
DLGAP2
Disks large-associated protein 2 is a protein that in humans is encoded by the DLGAP2 gene.

# Function
The product of this gene is one of the membrane-associated guanylate kinases localized at postsynaptic density in neuronal cells. These kinases are a family of signaling molecules expressed at various submembrane domains and contain the PDZ, SH3 and the guanylate kinase domains. This protein may play a role in the molecular organization of synapses and in neuronal cell signaling. Alternatively spliced transcript variants encoding different isoforms have been identified, but their full-length nature is not known.

# Interactions
DLGAP2 has been shown to interact with DLG4, the canonical synapse marker protein, which in turn binds to N-methyld-aspartate (NMDA) receptors and Shaker-type K+ channels.

# Clinical significance
As with many other synaptic genes, including its binding partner Shank2, DLGAP2 has been shown to be associated with Autism.
DNAJB6
DnaJ homolog subfamily B member 6 is a protein that in humans is encoded by the DNAJB6 gene.

# Function
This gene encodes a member of the DNAJ protein family. DNAJ family members are characterized by a highly conserved amino acid stretch called the 'J-domain' and function as one of the two major classes of molecular chaperones involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. This family member may also play a role in polyglutamine aggregation in specific neurons. Alternative splicing of this gene results in multiple transcript variants; however, not all variants have been fully described.

# Interactions
DNAJB6 has been shown to interact with Keratin 18. It has been also shown that the aggregation of A42 (a process involved in e.g. Alzheimer's disease) is retarded by DNAJB6 in a concentration-dependent manner, extending to very low sub-stoichiometric molar ratios of chaperone to peptide.
DNMT3B
DNA (cytosine-5-)-methyltransferase 3 beta, is an enzyme that in humans in encoded by the DNMT3B gene.  Mutation in this gene are associated with immunodeficiency, centromere instability and facial anomalies syndrome.

# Function
CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase which is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes primarily to the nucleus and its expression is developmentally regulated. Eight alternatively spliced transcript variants have been described. The full length sequences of variants 4 and 5 have not been determined.

# Clinical significance
immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome is a result of defects in lymphocyte maturation resulting from aberrant DNA methylation caused by mutations in the DNMT3B gene.
Variants of the gene can also contribute to nicotine dependency.

# Interactions
DNMT3B has been shown to interact with:
- CBX5,
- DNMT1,
- DNMT3A,
- KIF4A,
- NCAPG,
- SMC2,
- SUMO1  and
- UBE2I.
MD/PhD
MD/PhD or DO/PhD refers to an education which includes both the medical training of a doctor (MD or DO) with the rigor of a scientific researcher (PhD).  It can refer to the designation given to a person who has graduated from such an education, or an educational program which incorporates both curriculums.

# Profession
An MD/PhD or DO/PhD is usually more focused on research than a regular MD or DO.  Regular doctors can also do research, but, all other things equal, the PhD degree usually allows a better chance for getting research positions and grant acceptance.

# Educational program
The dual degree program at a university is a selective, mostly underwritten program which produces medical doctors who wish to also focus on research.  The applicants to a combined degree vs. a regular MD or DO degree lie mainly in the amount of research experience they have already attained, and the competitive nature of the degree (due to the usually free tuition and stipend) means that the grades and scores are usually higher, also.
The National Institutes of Health (NIH) has developed a grant to underwrite some universities' MD/PhD programs, called Medical Scientist Training Program.
DPAGT1
UDP-N-acetylglucosaminedolichyl-phosphate N-acetylglucosaminephosphotransferase is an enzyme that in humans is encoded by the DPAGT1 gene.
Mutations in DPAGT1 cause                 myasthenia            .Selcen, D; Shen, X. M.; Brengman, J; Li, Y; Stans, A. A.; Wieben, E; Engel, A. G. (2014). "DPAGT1 myasthenia and myopathy: Genetic, phenotypic, and expression studies". Neurology. 82 (20): 182230. doi:10.1212/WNL.0000000000000435. PMC 4035711. PMID 24759841..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
The protein encoded by this gene is an enzyme that catalyzes the first step in the dolichol-linked oligosaccharide pathway (also see Genetic pathway) for glycoprotein biosynthesis. This enzyme belongs to the glycosyltransferase family 4. This protein is an integral membrane protein of the endoplasmic reticulum. The congenital disorder of glycosylation type Ij is caused by mutation in the gene encoding this enzyme. Alternatively spliced transcript variants encoding different isoforms have been identified.
DYRK1A
Dual specificity tyrosine-phosphorylation-regulated kinase 1A is an enzyme that in humans is encoded by the DYRK1A gene. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region. These variants encode at least five different isoforms.

# Function
DYRK1A is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. This member contains a nuclear targeting signal sequence, a protein kinase domain, a leucine zipper motif, and a highly conservative 13-consecutive-histidine repeat. It catalyzes its autophosphorylation on serine/threonine and tyrosine residues. It may play a significant role in a signaling pathway regulating cell proliferation and may be involved in brain development.  This gene is a homolog of Drosophila mnb (minibrain) gene and rat Dyrk gene.
Dyrk1a has also been shown to modulate plasma homocysteine level in a mouse model of overexpression.

# Clinical significance
DYRK1A is localized in the Down syndrome critical region of chromosome 21, and is considered to be a strong candidate gene for learning defects associated with Down syndrome. In addition, a polymorphism (SNP) in DYRK1A was found to be associated with HIV-1 replication in monocyte-derived macrophages, as well as with slower progression to AIDS in two independent cohorts of HIV-1-infected individuals.  Mutations in DYRK1A are also associated with Autism spectrum disorder.

# Interactions
DYRK1A has been shown to interact with WDR68.
DYRK1B
Dual specificity tyrosine-phosphorylation-regulated kinase 1B is an enzyme that in humans is encoded by the DYRK1B gene.

# Function
DYRK1B is a member of the DYRK family of protein kinases.  DYRK1B contains a bipartite nuclear localization signal and is found mainly in muscle and testis.  The protein is proposed to be involved in the regulation of nuclear functions.  Three isoforms of DYRK1B have been identified differing in the presence of two alternatively spliced exons within the catalytic domain.

# Interactions
DYRK1B has been shown to interact with:
- PCBD1  and
- RANBP9.

# Clinical significance
One lone missense mutation in Dyrk1B gene (R102C) was found associated with an autosomal dominant early onset Coronary Artery Disease, juvenile-onset truncal obesity, severe hypertension, and type II diabetes mellitus - seen in subjects from a nomadic group in Iran.
Lipase

# Overview
A lipase is a water-soluble enzyme that catalyzes the hydrolysis of ester bonds in waterinsoluble, lipid substrates. Lipases thus comprise a subclass of the esterases.
Lipases are ubiquitous throughout living organisms, and genes encoding lipases are even present in certain viruses. 

# Function
Most lipases act at a specific position on the glycerol backbone of a lipid substrate (A1, A2 or A3).
In the example of human pancreatic lipase (HPL), which is the main enzyme responsible for breaking down fats in the human digestive system, a lipase acts to convert triglyceride substrates found in oils from food to monoglycerides and free fatty acids.
Myriad other lipase activities exist in nature, especially when the phospholipases and sphingomyelinases are considered.

# Structure
While a diverse array of genetically distinct lipase enzymes are found in nature, and represent several types of protein folds and catalytic mechanisms, most are built on an alpha/beta hydrolase fold  (see image) and employ a chymotrypsin-like hydrolysis mechanism involving a serine nucleophile, an acid residue (usually aspartic acid), and a histidine.

# Location of action
Some lipases work within the interior spaces of living cells to degrade lipids.
- In the example of lysosomal lipase, the enzyme is confined within an organelle called the lysosome.
- Other lipase enzymes, such as pancreatic lipases, are found in the spaces outside of cells and have roles in the metabolism, absorption and transport of lipids throughout the body.
As biological membranes are integral to living cells and are largely composed of phospholipids, lipases play important roles in cell biology.
Furthermore, lipases are involved in diverse biological processes ranging from routine metabolism of dietary triglycerides to cell signaling and inflammation.

# Lipases of Humans
The main lipases in the human digestive system are human pancreatic lipase (HPL) and pancreatic lipase related protein 2 (PLRP2), which are secreted by the pancreas. Humans also have several other related enzymes, including hepatic lipase (HL), endothelial lipase, and lipoprotein lipase. Not all of these lipases function in the gut (see table).
Other lipases include LIPH, LIPI, LIPJ, LIPK, LIPM, and LIPN.
There also are a diverse array of phospholipases, but these are not always classified with the other lipases.

# Industrial Uses
Lipases from fungi and bacteria serve important roles in human practices as ancient as yogurt and cheese fermentation. However, lipases are also being exploited as cheap and versatile catalysts to degrade lipids in more modern applications. For instance, a biotechnology company has brought recombinant lipase enzymes to market for use in applications such as baking, laundry detergents and even as biocatalysts  in alternative energy strategies to convert vegetable oil into fuel. 

## Differential Diagnosis of Abnormalities in Lipase

## Increased Lipase
- Zinc acetate
- Pancreatitis

# Additional images
- General formula of a carboxylate ester
- Glycerol
- General structure of a triglyceride
Pyuria
To view a comprehensive algorithm of common findings of urine composition and urine output, click here

# Overview
Pyuria is a condition in which urine contains  10 or more white cells/mm3. Gram stain and leukocyte esterase might be positive. Pyuria might be a sign of a bacterial or non bacterial urinary tract infection, genitourinary abnormalities, inflammatory disorders, and systemic diseases. Pyuria may be classified into sterile pyuria or bacteriuria. Treatment is not required for pyuria. However, underlying diseases must be treated.

# Definition
Pyuria is a condition in which urine contains pus. Definition of pyuria is as follow:
- Presence of 10 or more white cells/mm3 in a urine specimen
- Positive result on Grams stain of an unspun urine specimen
- Positive leukocyte esterase on urinary dipstick test
Pyuria might be a sign of a bacterial or non bacterial urinary tract infection.

# Classification
Pyuria may be classified based on the presence of detectable infection as shown below:

# Pyuria Differential Diagnosis
Differentiating the diseases that can cause pyuria:
To review differential diagnosis of sterile pyuria, click here.

# Treatment
- Sterile pyuria
- Pathogen-directed antimicrobial therapy
- Renal Tuberculosis
- Preferred regimen: (Isoniazid 300 mg PO qd for 2 months AND Rifampicin 450-600 mg qd for 2 months AND Ethambutol 15-25 mg/kg PO qd for 2 months AND Pyrazinamide 1500 mg for 2 months) THEN (Isoniazid 300 mg PO qd for 4-6 months AND Rifampicin 450-600 mg qd for 4-6 months)
- Gonorrhea
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose THEN (Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days)
- Chlamydia
- Preferred regimen: Azithromycin 1 g PO in single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 7 days
- Mycoplasma and Ureaplasma
- Preferred regimen: Azithromycin OR Levofloxacin OR Moxifloxacin
- Genital herpes
- Preferred regimen: Acyclovir 400 mg PO tid for 710 days or Acyclovir 200 mg PO five times a day for 710 days OR Famciclovir 250 mg PO tid for 710 days OR Valacyclovir 1 g PO bid for 7 days
- Trichomoniasis
- Preferred regimen: Metronidazole 2 g PO in a single dose OR Tinidazole 2 g PO in a single dose
- Fungal infections
- Preferred regimen, Candida albicans: Fluconazole 100 mg PO qd for 2-5 days
- Preferred regimen, non-albicans Candida: Amphotericin B 0.1 mg/kg/day IV for 2-5 days OR Amphotericin B bladder irrigation 5-50 mg/L of sterile water qd for 2-5 days
- Schistosomiasis
- Preferred regimen: Praziquantel 20 mg/kg PO bid for 12 days
Tetany

# Overview
Tetany is a medical sign, the involuntary contraction of muscles, caused by diseases and other conditions that increase the action potential frequency. The muscle cramps caused by the disease tetanus are due to a blocking of the inhibition to the neurons that supply muscles and are not classified as tetany. Tetany has two meanings, though both are related to the muscular system.
- Tetany (action potential summation)
- Tetany (medical sign)
The terms "tetany" and "tetanus" are distinct.
Tetany must be distinguished from the following:
- Muscle twitches
- Cramps
- Carpopedal spasm

# Mechanism
When the membrane potential is upset, for instance by low levels of ions (such as calcium) in the blood (hypocalcaemia), neurons will depolarize too easily. In the case of hypocalcaemia, calcium ions are drawn away from their association with the voltage-gated sodium channels thus sensitising them. The upset to membrane potential is therefore caused by an influx of sodium to the cell, not directly by the hypocalcaemia. As a result, too many action potentials are sent to muscles causing spasm.

# Causes
The usual cause of tetany is lack of calcium, but excess of phosphate (high phosphate-to-calcium ratio) can also trigger the spasms.  Milk-and-alkali tetany is an example of this imbalance.
Underfunction of the parathyroid gland can lead to tetany.
Low levels of carbon dioxide causes tetany by altering the albumin binding of calcium such that the ionised (physiologically influencing) fraction of calcium is reduced; the most common reason for low carbon dioxide levels is hyperventilation.

# Diagnosis
The nineteenth-century clinician Professor Armand Trousseau devised the trick of occluding the brachial artery by squeezing to trigger the cramps in the fingers (Trousseau sign).

# Differential Diagnosis
In alphabetical order In alphabetical order.  
- Addisonian crisis
- After multiple transfusions
- Alcoholism
- Brain injury
- Burns
- Cirrhosis
- Conn's Syndrome
- Diabetic precoma
- Drugs such as Oxcarbazepine
- Hemolytic crisis
- Hypercalcemia
- Hyperkalemic tetany
- Hyperventilation
- Hypocalcemia
- Hypoparathyroidism
- Intoxication
- Lack of Vitamin D
- Lactation
- Long term diuretic medication
- Malabsorbtion syndrome
- Neuropathy
- Pancreatitis
- Pregnancy
- Pseudohypoparathyroidism
- Recurring vomiting
- Renal failure
- Toxins
- Uncontrolled intravenous potassium supply
- Zollinger-Ellison Syndrome
Deanol

# Overview
Dimethylaminoethanol, also known as dimethylethanolamine (DMAE and DMEA respectively), is a primary alcohol. This compound also goes by the names of N,N-dimethyl-2-aminoethanol, beta-dimethylaminoethyl alcohol, beta-hydroxyethyldimethylamine and Deanol. It is a transparent, pale-yellow liquid.

# Biochemical significance
Dimethylaminoethanol is related to choline and may be a biochemical precursor to the neurotransmitter acetylcholine, although this conclusion has been disputed based on a 1977 rat experiment.  It is commonly believed that dimethylaminoethanol is methylated to produce choline in the brain, but this has been shown not to be the case (in a rat experiment). It is known that dimethylaminoethanol is processed by the liver into choline; however, in a rat experiment the choline molecule is charged and cannot pass the bloodbrain barrier. In the brain, DMAE is instead bound to phospholipids in place of choline to produce phosphatidyl-dimethylaminoethanol. This is then incorporated into nerve membranes, increasing fluidity and permeability, and acting as an antioxidant.

# Uses

## Industrial uses
Dimethylaminoethanol is used as a curing agent for polyurethanes and epoxy resins. It is also used in mass quantities for water treatment, and to some extent in the coatings industry. It is used in the synthesis of dyestuffs, textile auxiliaries, pharmaceuticals, emulsifiers, and corrosion inhibitors. It is also an additive to paint removers, boiler water and amino resins. It forms a number of salts with melting points below room temperature (ionic liquids) such as N,N-dimethylethanolammonium acetate and N,N-dimethylethanolammonium octanoate, which have been used as alternatives to conventional solvents.
2-Dimethylaminoethyl chloride hydrochloride is an intermediate made from dimethylaminoethanol that is widely used for the manufacture of pharmaceuticals.

## Biomedical research
Short-term studies have shown an increase in vigilance and alertness with a positive influence on mood following administration of DMAE, vitamins, and minerals in individuals suffering from borderline emotional disturbance. Research for ADHD has been promising, though inconclusive. A study showed dimethylaminoethanol to decrease the average life span of aged quail. Three other studies showed an increase in lifespan of mice 
The bitartrate salt of DMAE, i.e. 2-dimethylaminoethanol (+)-bitartrate, is sold as a dietary supplement. It is a white powder providing 37% DMAE.