Persius/hicric huggingface dataset:
GMP synthase (glutaminehydrolysing)
Guanosine monophosphate synthetase, (EC 6.3.5.2) also known as GMPS is an enzyme that converts xanthosine monophosphate to guanosine monophosphate.
In the de novo synthesis of purine nucleotides, IMP is the branch point metabolite at which point the pathway diverges to the synthesis of either guanine or adenine nucleotides. In the guanine nucleotide pathway, there are 2 enzymes involved in converting IMP to GMP, namely IMP dehydrogenase (IMPD1), which catalyzes the oxidation of IMP to XMP, and GMP synthetase, which catalyzes the amination of XMP to GMP.

# Enzymology
In enzymology, a GMP synthetase (glutamine-hydrolysing) (EC 6.3.5.2) is an enzyme that catalyzes the chemical reaction
The 4 substrates of this enzyme are ATP, xanthosine 5'-phosphate, L-glutamine, and H2O, whereas its 4 products are AMP, diphosphate, GMP, and L-glutamate.
This enzyme belongs to the family of ligases, specifically those forming carbon-nitrogen bonds carbon-nitrogen ligases with glutamine as amido-N-donor.  The systematic name of this enzyme class is xanthosine-5'-phosphate:L-glutamine amido-ligase (AMP-forming). Other names in common use include GMP synthetase (glutamine-hydrolysing), guanylate synthetase (glutamine-hydrolyzing), guanosine monophosphate synthetase (glutamine-hydrolyzing), xanthosine 5'-phosphate amidotransferase, and guanosine 5'-monophosphate synthetase.  This enzyme participates in purine metabolism and glutamate metabolism.  At least one compound, Psicofuranin is known to inhibit this enzyme.

# Structural studies
As of late 2007, 5 structures have been solved for this class of enzymes, with PDB accession codes 1GPM, 1WL8, 2A9V, 2D7J, and 2DPL.
G protein-coupled bile acid receptor
The G protein-coupled bile acid receptor 1 (GPBAR1) also known G-protein coupled receptor 19 (GPCR19), membrane-type receptor for bile acids (M-BAR) or TGR5 as is a protein that in humans is encoded by the GPBAR1 gene.

# Function
This gene encodes a member of the G protein-coupled receptor (GPCR) superfamily. This protein functions as a cell surface receptor for bile acids. Treatment of cells expressing this GPCR with bile acids induces the production of intracellular cAMP, activation of a MAP kinase signaling pathway, and internalization of the receptor. The receptor is implicated in the suppression of macrophage functions and regulation of energy homeostasis by bile acids.
One effect of this receptor is to activate deiodinases which convert the prohormone thyroxine (T4) to the active hormone triiodothyronine (T3).  T3 in turn activates the thyroid hormone receptor which increases metabolic rate.
Guanidinoacetate N-methyltransferase
Guanidinoacetate N-methyltransferase (EC 2.1.1.2) is an enzyme that catalyzes the chemical reaction and is encoded by gene GAMT located on chromosome 19p13.3.
Thus, the two substrates of this enzyme are S-adenosyl methionine and guanidinoacetate, whereas its two products are S-adenosylhomocysteine and creatine.
This enzyme belongs to the family of transferases, specifically those transferring one-carbon group methyltransferases.  The systematic name of this enzyme class is S-adenosyl-L-methionine:N-guanidinoacetate methyltransferase. Other names in common use include GA methylpherase, guanidinoacetate methyltransferase, guanidinoacetate transmethylase, methionine-guanidinoacetic transmethylase, and guanidoacetate methyltransferase.  This enzyme participates in glycine, serine and threonine metabolism and arginine and proline metabolism.
The protein encoded by this gene is a methyltransferase that converts guanidoacetate to creatine, using S-adenosylmethionine as the methyl donor. Defects in this gene have been implicated in neurologic syndromes and muscular hypotonia, probably due to creatine deficiency and accumulation of guanidinoacetate in the brain of affected individuals. Two transcript variants encoding different isoforms have been described for this gene.

# Structural studies
As of late 2007, 7 structures have been solved for this class of enzymes, with PDB accession codes 1KHH, 1P1B, 1P1C, 1XCJ, 1XCL, 1ZX0, and 2BLN.
X-linked lymphoproliferative disease
Synonyms and keywords: Hereditary lymphoproliferative disease

# Overview
X-linked lymphoproliferative disease is a lymphoproliferative disorder.  There is a mutation on the X chromosome that has been found to be associated with a T and NK cell lymphoproliferative disorder. The mutation is on the long arm of the chromosome, at position 25, which is denoted as Xq25. At this position, there is a deletion in the SH2D1A gene, which codes for an SH2 domain on a signal transducing protein called SLAM-associated protein (SAP).
The term SH2 domain stands for src-homology 2 domain, which is a three-dimensional domain structure of about 100 amino acid residues. These domains are present in many signaling proteins because they permit specific, non-covalent bonding to proteins that contain phosphotyrosines. The amino acid residues adjacent to the phosphotyrosine on the target protein are what determine the unique binding specificity.
The SAP protein is important in the signaling events that activate T and NK cells because it functions as an intracellular adapter that transduces T and NK cell activation. Normally, the SAP protein is expressed in the cytoplasm of T and NK cells, where it binds to the cytoplasmic domain of the surface receptor called Signaling Lymphocyte Activation Molecule (SLAM). This binding initiates a signal transduction pathway, which results in the modulation of IFN-. A deletion in the SH2D1A gene leads to a non-functional SH2 domain on the SAP protein, which means it is unable to bind to the SLAM molecule, leading to a lack of modulation of IFN-, causing uncontrolled cell proliferation.
Strangely, in boys with X-linked lymphoproliferative disorder there is an overwhelming T-cell mediated response to the Epstein-Barr virus (EBV), which often leads to death from bone marrow failure, irreversible hepatitis, and malignant lymphoma. However, the connection between EBV and X-linked lymphoproliferative disorder is yet to be determined.
Hydroxyacyl-Coenzyme A dehydrogenase
Hydroxyacyl-Coenzyme A dehydrogenase also known as HADH is an enzyme which in humans is encoded by the HADH  gene.

# Structure
The HADH gene is located on the 4th chromosome, with its specific location being identified as 4q22-q26. The gene has 10 exons. The HADH gene encodes a 34.3 kDa protein that has 314 amino acids and 124 observed peptides.

# Function
This gene is a member of the 3-hydroxyacyl-CoA dehydrogenase gene family. The encoded protein functions in the mitochondrial matrix to catalyze the oxidation of straight-chain 3-hydroxyacyl-CoAs as part of the beta-oxidation pathway. Its enzymatic activity is highest with medium-chain-length fatty acids.

# Clinical significance
Mutations in this gene cause one form of familial hyperinsulinemic hypoglycemia.  A deficiency is associated with 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. Mutations also cause 3-hydroxyacyl-CoA dehydrogenase deficiency. There are a wide variety of mutations that have been identified to cause this disease. Among them are missense mutations (A40T, P258L, D57G, Y226H) and nonsense mutations (R236X) in the protein, and splicing mutations (261+1G>A, 710-2A>G) and some small deletions (587delC) in the cDNA. One mutation, 636+471G>T in the HADH gene, was shown to create a cryptic splice donor site and an out-of-frame pseudoexon. Most of the described cases have homozygous mutations. This disease has fairly homogenous clinical presentation across cases. The symptoms first appear in early life, between 1.5 hours post birth and 3 years of age, and the most common symptoms are hypoglycemia and seizures/convulsions directly related to the hypoglycemia. There are other clinical presentations that have been identified, namely: myoglobinuria, dicarboxylic aciduria, feeding difficulties in infancy, muscular hypotonia, hepatic steatosis, growth delay, hypertrophic cardiomyopathy, dilated cardiomyopathy, hepatic necrosis, and fulminant hepatic failure. The disorder may be diagnosed by either the analysis of the molecular genetics of the individual, or by detection of abnormal metabolite levels in blood and/or plasma. Individuals with this deficiency have an elevated amount of 3-hydroxyglutarate excreted through the urine; a heightened level of C4-OH acylcarnitine in the blood plasma is also a characteristic of this FAO disorder. Most documented cases thus far have shown that individuals are responsive to diazoxide treatment, and highlight the need for diagnosis and treatment administration as early as possible in order to correct hypoglycemia and avoid irreversible brain damage.

# Interactions
HADH has been shown to interact with Vpr, such that HIV-1 Vpr regulates mitochondrial respiration and enhances the activity of hydroxyacyl-CoA dehydrogenase (HADH) through PPARbeta/delta.
Hypophyseal hypertrophy in pregnancy

# Overview
Hypophyseal hypertrophy in pregnancy refers to enlargement of the pituitary gland during pregnancy.

# Pathophysiology
MRI studies indicate that the pituitary gland increases in volume by about 30% during pregnancy. It tends to bulge upward.

# Natural History, Complications and Prognosis
Rarely does the enlarged pituitary gland impinge on the optic chiasm and cause visual field changes.  The pituitary returns to normal size after delivery.  Despite the hyperplasia of the pituitary gland, there is no increased risk of pituitary tumors like a prolactinoma.
Interleukin 5 receptor alpha subunit
Interleukin 5 receptor, alpha (IL5RA) also known as CD125 (Cluster of Differentiation 125) is a subunit of the Interleukin-5 receptor. IL5RA also denotes its human gene.

# Function
The protein encoded by this gene is an interleukin 5 specific subunit of a heterodimeric cytokine receptor. The receptor is composed of a ligand specific alpha subunit and a signal transducing beta subunit shared by the receptors for interleukin 3 (IL3), colony stimulating factor 2 (CSF2/GM-CSF), and interleukin 5 (IL5). The binding of this protein to IL5 depends on the beta subunit. The beta subunit is activated by the ligand binding, and is required for the biological activities of IL5. This protein has been found to interact with syndecan binding protein (syntenin), which is required for IL5 mediated activation of the transcription factor SOX4. Six alternatively spliced transcript variants encoding three distinct isoforms have been reported.

# Interactions
Interleukin 5 receptor alpha subunit has been shown to interact with:
- Interleukin 5,
- Janus kinase 2,
- Protein unc-119 homolog,  and
- SDCBP
IMITREX spray nonclinical toxicology

# Nonclinical Toxicology

### Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis: In carcinogenicity studies in mouse and rat in which sumatriptan was administered orally for 78 and 104 weeks, respectively, there was no evidence in either species of an increase in tumors related to sumatriptan administration.
Carcinogenicity studies of sumatriptan using the nasal route have not been conducted.
Mutagenesis: Sumatriptan was negative in in vitro(bacterial reverse mutation , gene cell mutation in Chinese hamster V79/HGPRT, chromosomal aberration in human lymphocytes) and in vivo (rat micronucleus) assays.
Impairment of Fertility: When sumatriptan was administered by subcutaneous injection to male and female rats prior to and throughout the mating period, there was no evidence of impaired fertility at doses up to 60 mg/kg/day. When sumatriptan (5, 50, or 500 mg/kg/day) was administered orally to male and female rats prior to and throughout the mating period, there was a treatment-related decrease in fertility secondary to a decrease in mating in animals treated with doses greater than 5 mg/kg/day. It is not clear whether this finding was due to an effect on males or females or both.
Fertility studies of sumatriptan using the intranasal route have not been conducted.

### Animal Toxicology and/or Pharmacology
Corneal Opacities: Dogs receiving oral sumatriptan developed corneal opacities and defects in the corneal epithelium. Corneal opacities were seen at the lowest dose tested, 2 mg/kg/day, and were present after 1 month of treatment. Defects in the corneal epithelium were noted in a 60week study. Earlier examinations for these toxicities were not conducted and no-effect doses were not established.
IMITREX tablet indications and usage

# Indications and Usage
IMITREX Tablets are indicated for the acute treatment of migraine with or without aura in adults.

### Limitations of Use
- Use only if a clear diagnosis of migraine headache has been established. If a patient has no response to the first migraine attack treated with IMITREX, reconsider the diagnosis of migraine before IMITREX is administered to treat any subsequent attacks.
- IMITREX is not indicated for the prevention of migraine attacks.
- Safety and effectiveness of IMITREX Tablets have not been established for cluster headache.
Incidence of stent thrombosis in BMS
Multiple contemporary studies involving  single center and multi center experience suggests an overall incidence of 0.5 % - 2.5 %. (1,2,3,4,5) There is some variation of these numbers with the definitions used. For instance, in a recent study of 8847 patients who received a BMS, a cumulative incidence of definite, probable or possible ST over 15 months was 2.15% and that for definite ST was 0.61% (6) In a study involving serial angioscopy after sirolimus-eluting stent (SES) implantation at 4, 11, and 21.2 2.2 months no BMS had thrombus in 11 patients. (11)

# Incidence of early ST in BMS
- For purposes of discussion this group would include
intra-procedural ST
acute ST up to 24 hrs
subacute  24 hrs to 30 days
- intra-procedural ST
- acute ST up to 24 hrs
- subacute  24 hrs to 30 days
In the current environment the overall incidence of acute ST with BMS is   0.5%.
In study of 7484 patients with (intra vascular ultrasound study) IVUS before and after stenting, incidence of ST was 0.4% up to a week. The median time of ST was 24 hours and the minimum time was 1 hour. (7)
In the current environment the overall incidence of acute ST with BMS is   0.5%
In a retrospective analysis 4509 patients the rate of subacute ST was 0.51%. (8)
In a study of 7484 patients with IVUS interrogation of the stent, ST of 0.4% was reported up to one week with a median time of 24 hours. (7)
The incidence of subacute ST could be higher in special patient populations. In a group of 40 patients who underwent non cardiac surgery following BMS, the incidence of ST while on two antiplatelet agents appeared to be 2.5 % (one patient out of 40).  (9)

# Incidence of late ST of BMS

## For purposes of discussion this would include ST from 30 days till up to 3 years or longer
- This would include
Late ST             > 30 days to one year
Very late ST        > more than one year, but generally less than 3 years
Later than 3  years
- Late ST             > 30 days to one year
- Very late ST        > more than one year, but generally less than 3 years
- Later than 3  years
The reported incidence in this group ranges between 0-0.5%. Given the paucity of data only assumptions can be made for the group beyond 1-3 years.
The incidence of late ST with BMS was 0.28% in a meta-analysis of 14 trials looking at 6675 patients. (10)
It appears that ST in the very late group is exceedingly rare.
In a meta-analysis of 14 trials looking at 6675 patients no patient presentetd with very late ST of BMS. How ever regular follow up of most patients confined to one year or less. (10)

# Back to Stent Thrombosis page
Incomplete right bundle branch block
Synonyms and keywords: right bundloid pattern; rsr pattern

# Overview
In incomplete right bundle branch block, the QRS interval is widened, but is insufficiently prolonged to meet the criteria for right bundle branch block.

# Diagnosis

## Electrocardiogram
- Incomplete RBBB is defined by QRS duration between 110 and 120 ms in adults, between 90 and 100 ms in children between 4 and 16 years of age, and between 86 and 90 ms in children less than 8 years of age.
- Other criteria are the same as for complete RBBB.
- In children, incomplete RBBB may be diagnosed when the terminal rightward deflection is less than 40 ms but greater than or equal to 20 ms.
- The ECG pattern of incomplete RBBB may be present in the absence of heart disease, particularly when the V1 lead is recorded higher than or to the right of normal position and r is less than 20 ms.
- The terms rsr and normal rsr are not recommended to describe such patterns, because their meaning can be variously interpreted. In children, an rsr pattern in V1 and V2 with a normal QRS duration is a normal variant.
Interferon alfa-2a drug interactions

# Drug Interactions
Roferon-A has been reported to reduce the clearance of theophylline.10,11 The clinical relevance of this interaction is presently unknown. Caution should be exercised when administering Roferon-A in combination with other potentially myelosuppressive agents. Synergistic toxicity has been observed when Roferon-A is administered in combination with zidovudine (AZT) (see WARNINGS: Bone Marrow Toxicity).
In transplant recipients, therapeutic immunosuppression may be weakened because interferons also exert an immunostimulatory action.
Alpha-interferons may affect the oxidative metabolic process by reducing the activity of hepatic microsomal cytochrome enzymes in the P450 group. Although the clinical relevance is still unclear, this should be taken into account when prescribing concomitant therapy with drugs metabolized by this route.
The neurotoxic, hematotoxic or cardiotoxic effects of previously or concurrently administered drugs may be increased by interferons. Interactions could occur following concurrent administration of centrally acting drugs. Use of Roferon-A in conjunction with interleukin-2 may potentiate risks of renal failure.
International Prostate Symptom Score
Steven C. Campbell, M.D., Ph.D.

# Overview
The International Prostate Symptom Score (IPSS) is an 8 question (7 symptom questions + 1 quality of life question) written screening tool used to screen for, rapidly diagnose, track the symptoms of, and suggest management of the symptoms of the disease Benign Prostatic Hyperplasia (BPH). Created in 1992 by the American Urological Association, it originally lacked the 8th QOL question, hence its original name: the American Urological Association symptom score (AUA-7).
The IPSS was designed to be self-administered by the patient, with speed and ease in mind. Hence, it can be used in both urology clinics as well as the clinics of primary care physicians (i.e. by general practitioners) for the diagnosis of BPH.
Additionally, the IPSS can be performed multiple times to compare the progression of symptoms and their severity over months and years.
In addition to diagnosis and charting disease progression, the IPSS is effective in helping to determine treatment for patients. Patients with benign prostatic hyperplasia (BPH) either 1) may need no treatment, just observation, because many patients stay the same or even improve over the years, or 2) many need only medical treatment, a) either only with an alpha-1-adrenergic antagonist, e.g. tamsulosin, or b) with an alpha-1-adrenergic antagonist plus finasteride, depending on the severity of their symptoms, or 3) may need surgical intervention.    
BPH patients are treated with surgery if a) BPH becomes a risk factor for upper urinary tract damage (i.e. damage to the ureters and kidneys, which may include severe damage such as pyelonephritis, hydronephrosis, and renal failure), or b) if the symptoms of BPH on the lower urinary tract become serious (i.e. 1) recurrent infections, or 2) bladder decompensation, i.e. urinary retention >25% immediately after voiding the bladder). In all non-emergency cases, not only the severity of BPH symptoms, but also the subjective quality-of-life of the patient and the wishes of the patient are taken into account before deciding on surgery.
The IPSS is available free-of-charge on the Internet. See: 
Or see:
Journal of Machine Learning Research
The Journal of Machine Learning Research (usually abbreviated JMLR), is a scientific journal focusing on machine learning, a subfield of artificial intelligence. It was founded in 2000.
The journal was founded as an open-access alternative to the journal Machine Learning.  In 2001, forty editors of Machine Learning resigned in order to support JMLR, saying that in the era of the internet, it was detrimental for researchers to continue publishing their papers in expensive journals with pay-access archives.  Instead, they wrote, they supported the model of JMLR, in which authors retained copyright over their papers and archives were freely available on the internet.
Since Summer 2007 JMLR is also publishing Machine Learning Open Source Software .

# Reference
Lecithin-cholesterol acyltransferase
Synonyms and keywords: LCAT; phosphatidylcholine-sterol O-acyltransferase

# Overview
Lecithin-cholesterol acyltransferase is an enzyme that catalyzes the esterification of free cholesterol.
Lecithin + Cholesterol  Lysolecithin + Cholesteryl ester

# Historical Perspective
In 1935, Sperry first recognized the esterification of free cholesterol occurred when human plasma was incubated at 37C and considered it as an enzymatic process since the effect was abolished when the plasma was heated to 55-60C. In 1962, Glomset identified the enzyme lecithin-cholesterol acyltransferase (LCAT) that accounts for esterification of most of the free cholesterol in plasma.

# Biochemistry
Lecithin-cholesterol acyltransferase catalyzes the esterification of the free cholesterol into chlesteryl ester by transferring an acyl chain from the R2 position of a phosphatidylcholine to the 3-hydroxy residue of cholesterol. Cholesteryl ester is then sequestered into the core of a lipoprotein particle eventually making the newly synthesized HDL spherical and forcing the reaction to become unidirectional since the particles are removed from the surface. Its role in extracellular cholesterol metabolism may facilitate the uptake of cholesterol from peripheral tissues into HDL particles by maintaining a concentration gradient for the efflux of free cholesterol which is centrol to reverse cholesterol transport (RCT). The enzyme is bound to high-density lipoprotein (HDL) and low-density lipoprotein (LDL) in the plasma.
Lamivudine dosage and administration

# dosage and administration

## Adults and Adolescents >16 years of age
The recommended oral dose of EPIVIR in HIV-1-infected adults and adolescents aged >16 years is 300 mg daily, administered as either 150 mg twice daily or 300 mg once daily, in combination with other antiretroviral agents. If lamivudine is administered to a patient infected with HIV-1 and HBV, the dosage indicated for HIV-1 therapy should be used as part of an appropriate combination regimen .

## Pediatric Patients
The recommended oral dose of EPIVIR Oral Solution in HIV-1-infected pediatric patients aged 3 months to 16 years is 4 mg/kg twice daily (up to a maximum of 150 mg twice a day), administered in combination with other antiretroviral agents.
EPIVIR is also available as a scored tablet for HIV-1-infected pediatric patients who weigh 14 kg and for whom a solid dosage form is appropriate. Before prescribing EPIVIR Tablets, children should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow EPIVIR Tablets, the oral solution formulation should be prescribed. The recommended oral dosage of EPIVIR Tablets for HIV-1-infected pediatric patients is presented in Table 1.

## Patients With Renal Impairment
Dosing of EPIVIR is adjusted in accordance with renal function. Dosage adjustments are listed in Table 2 .
No additional dosing of EPIVIR is required after routine (4-hour) hemodialysis or peritoneal dialysis.
Although there are insufficient data to recommend a specific dose adjustment of EPIVIR in pediatric patients with renal impairment, a reduction in the dose and/or an increase in the dosing interval should be considered.