Persius/hicric huggingface dataset:
Extracellular signal-regulated kinases
In molecular biology, extracellular signalregulated kinases (ERKs) or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells.  Many different stimuli, including growth factors, cytokines, virus infection, ligands for  heterotrimeric G protein-coupled receptors, transforming agents, and carcinogens, activate the ERK pathway.
The term, "extracellular signalregulated kinases", is sometimes used as a synonym for mitogen-activated protein kinase (MAPK), but has more recently been adopted for a specific subset of the mammalian MAPK family.
In the MAPK/ERK pathway, Ras activates c-Raf, followed by mitogen-activated protein kinase kinase (abbreviated as MKK, MEK, or MAP2K) and then MAPK1/2 (below).  Ras is typically activated by growth hormones through receptor tyrosine kinases and GRB2/SOS, but may also receive other signals.  ERKs are known to activate many transcription factors, such as ELK1, and some downstream protein kinases.
Disruption of the ERK pathway is common in cancers, especially Ras, c-Raf and receptors such as HER2.

# Mitogen-activated protein kinase 1
Mitogen-activated protein kinase 1 (MAPK1) is also known as "extracellular signal-regulated kinase 2" (ERK2). Two similar (85% sequence identity) protein kinases were originally called ERK1 and ERK2. They were found during a search for protein kinases that are rapidly phosphorylated after activation of cell surface tyrosine kinases such as the epidermal growth factor receptor. Phosphorylation of ERKs leads to the activation of their kinase activity.
The molecular events linking cell surface receptors to activation of ERKs are complex. It was found that Ras GTP-binding proteins are involved in the activation of ERKs. Another protein kinase, Raf-1, was shown to phosphorylate a "MAP kinase-kinase", thus qualifying as a "MAP kinase kinase kinase". The MAP kinase-kinase, which activates ERK, was named "MAPK/ERK kinase" (MEK).
Receptor-linked tyrosine kinases, Ras, Raf, MEK, and MAPK could be fitted into a signaling cascade linking an extracellular signal to MAPK activation. See: MAPK/ERK pathway.
Transgenic gene knockout mice lacking MAPK1 have major defects in early development. Apart from developmental defects, under activity or lack of MAPK1 (Erk2) resist activation induced cell death in helper T cells which could cause autoimmunity due to T helper 17 persistence.

# Mitogen-activated protein kinase 3
Mitogen-activated protein kinase 3 (MAPK3) is also known as "extracellular signal-regulated kinase 1" (ERK1). Transgenic gene knockout mice lacking MAPK3 are viable and it is thought that MAPK1 can fulfill most MAPK3 functions in most cells. The main exception is in T cells. Mice lacking MAPK3 have  reduced T cell development past the CD4+CD8+ stage.
Equilibrative nucleoside transporter 1
Equilibrative nucleoside transporter 1 (ENT1) is a protein that in humans is encoded by the SLC29A1 gene. Multiple alternatively spliced variants, encoding the same protein, have been found for this gene.

# Function
This gene is a member of the equilibrative nucleoside transporter family. The gene encodes a transmembrane glycoprotein that localizes to the plasma and mitochondrial membranes and mediates the cellular uptake of nucleosides from the surrounding medium. The protein is categorized as an equilibrative (as opposed to concentrative) transporter that is sensitive to inhibition by nitrobenzylmercaptopurine ribonucleoside (NBMPR). Nucleoside transporters are required for nucleotide synthesis in cells that lack de novo nucleoside synthesis pathways, and are also necessary for the uptake of cytotoxic nucleosides used for cancer and viral chemotherapies.

# Genomics
The gene encoding this protein is located on the short arm of chromosome 6 at 6p21.2-p21.1 on the Watson (plus) strand. It is 14,647 bases in length. The encoded protein has 456 amino acid residues  with 11 predicted transmembrane domains. The predicted molecular weight is 50.219 kiloDaltons. The protein is post translationally glycosylated and expressed in all tissue with the apparent exception of skeletal muscle. The highest levels are found in the liver, heart, testis, spleen, lung, kidney and brain.

# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.
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# Clinical
Mutations in this gene have been associated with H syndrome, pigmented hypertrichosis with insulin dependent diabetes and Faisalabad histiocytosis.
Erythema nodosum (paitent information)
For the WikiDoc page for this topic, click here

# Overview
Erythema nodosum is an inflammatory disorder that is characterized by tender, red nodules under the skin.

# What are the symptoms of Erythema nodosum?
Erythema nodosum is most common on the shins, but it may also occur on other areas of the body (buttocks, calves, ankles, thighs, and arms).
The lesions begin as flat, firm, hot, red, painful lumps approximately an inch across. Within a few days they may become purplish, then over several weeks fade to a brownish, flat patch.
Other symptoms may include:
- Fever
- General ill feeling (malaise)
- Joint aches
- Skin redness, inflammation, or irritation
- Swelling of the leg or other affected area
The red and inflamed skin symptoms may regress to a bruise-like appearance.

# What causes Erythema nodosum?
In about half of cases, the exact cause of erythema nodosum is unknown. Some cases may be associated with the following:
- Infections. Some of the more common ones are:
- Streptococcus (most common)
- Cat scratch disease
- Chlamydia
- Coccidioidomycosis
- Hepatitis B
- Histoplasmosis
- Leptospirosis
- Mononucleosis (EBV)
- Mycobacteria
- Mycoplasma
- Psittacosis
- Syphilis
- Tuberculosis
- Tularemia
- Yersinia
- Pregnancy
- Sensitivity to certain medications, including:
- Amoxicillin and other penicillins
- Sulfonamides
- Sulfones
- Oral contraceptives
- Other antibiotics
- Progestin
Other associated disorders include leukemia, lymphoma, sarcoidosis, rheumatic fever, Bechet's disease, and ulcerative colitis.

# Who is at highest risk?
The condition is more common in women than it is in men.

# Diagnosis
The diagnosis is primarily based on the appearance of the skin nodules.
Punch biopsy of a nodule may show characteristic changes (septal panniculitis).
Throat culture may be done to reule out a strep infection.
Chest x-ray may be done to rule out sarcoidosis or tuberculosis.

# When to seek urgent medical care?
Call for an appointment with your health care provider if you develop symptoms of erythema nodosum.

# Treatment options
The underlying infection, drug, or disease should be identified and treated. Nonsteroidal anti-inflammatory medications (NSAIDs) may reduce symptoms. An oral potassium iodide (SSKI) solution may produce prompt resolution of the nodules.
Corticosteroids or salicylate medications may be needed to reduce acute inflammation. Analgesics and limitation of activity may be needed to control varying amounts of pain.
Topical therapy is not generally needed, although hot or cold compresses may reduce discomfort.

# Where to find medical care for Erythema nodosum?
Directions to Hospitals Treating Erythema nodosum

# What to expect (Outlook/Prognosis)?
Erythema nodosum is uncomfortable, but it is usually not dangerous. Symptoms typically disappear within about 6 weeks, but may recur.

# Sources
Erythema toxicum (patient information)
For the WikiDoc page for this topic, click here

# Overview
Erythema toxicum is a common, noncancerous skin condition seen in newborns.

# What are the symptoms of Erythema toxicum?
The main symptom is a rash of small, yellow-to-white colored papules surrounded by red skin. There may be a few or several papules. They usually appear on the face and middle of the body, but may also be seen on the upper arms and thighs.
The rash can change rapidly, appearing and disappearing in different areas over hours to days.

# What causes Erythema toxicum?
Its cause is unknown.
The condition may be present in the first few hours of life, generally appears after the first day, and may last for several days. Although the condition is harmless, it can be of great concern to the new parent.

# Who is at highest risk?
Erythema toxicum may appear in 50 percent or more of all normal newborn infants. It usually appears in term infants between the ages of 3 days and 2 weeks.

# Diagnosis
Examination by your health care provider during a routine well-baby exam is usually sufficient to make the diagnosis. No testing is usually needed.

# When to seek urgent medical care?
Discuss the condition with your health care provider during a routine examination if you are concerned.

# Treatment options
The large red splotches typically disappear without any treatment or changes in skin care.

# Where to find medical care for Erythema toxicum?
Directions to Hospitals Treating Erythema toxicum

# What to expect (Outlook/Prognosis)?
The rash usually clears within 2 weeks. It is usually completely gone by age 4 months.

# Possible complications
There are no complications.

# Sources
Far upstream element-binding protein 1
Far upstream element-binding protein 1 is a protein that in humans is encoded by the FUBP1 gene.
This gene encodes a ssDNA binding protein that activates the far upstream element (FUSE) of c-myc and stimulates expression of c-myc in undifferentiated cells. Regulation of FUSE by FUBP occurs through single-strand binding of FUBP to the non-coding strand. This protein has been shown to function as an ATP-dependent DNA helicase.

# Interactions
Far upstream element-binding protein 1 has been shown to interact with MAPK14 and SMN1.
Flap structure-specific endonuclease 1
Flap endonuclease 1 is an enzyme that in humans is encoded by the FEN1 gene.

# Function
The protein encoded by this gene removes 5' overhanging "flaps" (or short sections of single stranded DNA that "hang off" because their nucleotide bases are prevented from binding to their complementary base pairdespite any base pairing downstream) in DNA repair and processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis. Direct physical interaction between this protein and AP endonuclease 1 during long-patch base excision repair provides coordinated loading of the proteins onto the substrate, thus passing the substrate from one enzyme to another. The protein is a member of the XPG/RAD2 endonuclease family and is one of ten proteins essential for cell-free DNA replication. DNA secondary structure can inhibit flap processing at certain trinucleotide repeats in a length-dependent manner by concealing the 5' end of the flap that is necessary for both binding and cleavage by the protein encoded by this gene. Therefore, secondary structure can deter the protective function of this protein, leading to site-specific trinucleotide expansions.

# Interactions
Flap structure-specific endonuclease 1 has been shown to interact with:
- APEX1,
- BLM
- CDK2,
- CCNA2,
- EP300,
- HNRNPA1,
- PCNA,  and
- WRN.

# Over expression of FEN1 in cancers
FEN1 is over-expressed in the majority of cancers of the breast, prostate, stomach, neuroblastomas, pancreatic, and lung.
FEN1 is an essential enzyme in an inaccurate pathway for repair of double-strand breaks in DNA called microhomology-dependent alternative end joining or microhomology-mediated end joining (MMEJ).  MMEJ always involves at least a small deletion, so that it is a mutagenic pathway.  Several other pathways can also repair double-strand breaks in DNA, including the less inaccurate pathway of non-homologous end joining (NHEJ) and accurate pathways using homologous recombinational repair (HRR).  Various factors determine which pathway will be used for repair of double strand breaks in DNA.  When FEN1 is over-expressed (this occurs when its promoter is hypomethylated) the highly inaccurate MMEJ pathway may be favored, causing a higher rate of mutation and increased risk of cancer.
Cancers are very often deficient in expression of one or more DNA repair genes, but over-expression of a DNA repair gene is unusual in cancer.  For instance, at least 36 DNA repair enzymes, when mutationally defective in germ line cells, cause increased risk of cancer (hereditary cancer syndromes).  Similarly, at least 12 DNA repair genes have frequently been found to be epigenetically repressed in one or more cancers. (See also Epigenetically reduced DNA repair and cancer.)  Ordinarily, deficient expression of a DNA repair enzyme results in increased un-repaired DNA damages which, through replication errors (translesion synthesis), lead to mutations and cancer. However, FEN1 mediated MMEJ repair is highly inaccurate, so in this case, over-expression, rather than under-expression, leads to cancer.
Flavin-containing monooxygenase system
The Flavin-containing monooxygenase (FMO) system is used for oxidation reactions in drug metabolism.
The major difference between this system and the Cytochrome P450 monooxygenase system is that the FMO system does not act to oxidize carbon atoms.
Also in contrast to P450, the FMO system is not induced by exposure to drugs or environmental pollutants.
The FMO system is distinct from the cytrochrome P450 system in that it is non-inducible, does not have a heme prosthetic group but both require NADPH and oxygen; multiple isozymes are known for both; and they are both localized in microsomes of the endoplasmic reticulum.
Gonadotropin-releasing hormone agonist

# Overview
A gonadotropin-releasing hormone agonist (GnRH agonist) is a synthetic peptide modeled after the hypothalamic neurohormone  GnRH  that interacts with the gonadotropin-releasing hormone receptor to elicit its biologic response, the release of the pituitary hormones FSH and LH.
GnRH agonists are pregnancy category X drugs.

# Flare effect and downregulation
Agonists do not quickly dissociate from the GnRH receptor. As a result initially there is an increase in FSH and LH secretion (so-called "flare effect").
However after about ten days a profound hypogonadal effect is achieved through receptor downregulation. Generally this induced and reversible hypogonadism is the therapeutic goal.

# Agonists with double and single substitutions
GnRH agonists are synthetically modeled after the natural GnRH decapeptide with specific amino acid substitutions typically in position 6 and 10. These substitutions inhibit rapid degradation. Agonists with 2 substitutions include:
- leuprolide (Lupron, Eligard)
- buserelin (Suprefact, Suprecor)
- nafarelin (Synarel)
- histrelin (Supprelin)
- goserelin (Zoladex)
- deslorelin
Triptorelin is an agonist with only a single substitution at position 6.
- Leuprolide
- Buserelin
- Nafarelin
- Histrelin

# Administration
These medications can be administered intranasally, by injection, or by implant.  Injectables have been formulated for daily, monthly, and quarterly use; and implants can last from 1 to 3 months.

# Uses
GnRH agonists are useful in:
- Treatment of cancers that are hormonally sensitive and where a hypogonadal state decreases the chances of a recurrence. Thus they are commonly employed in the medical management of  prostate cancer and  have been used in patients with breast cancer.
- Treatment of  delaying puberty in individuals with precocious puberty.
- Management of female disorders that are dependent on estrogen productions. Women with menorrhagia, endometriosis. adenomyosis,  or uterine fibroids may receive GnRH agonists to suppress ovarian activity and induce a hypoestrogenic state.
- IVF therapy: they allow for better control of ovarian stimulation during the administration of exogenous FSH. Typically, after GnRH agonists have induced a state of hypoestrogenism, exogenous FSH is given to stimulate ovarian follicle, followed by human chorionic gonadotropins (hCG)  to trigger ovulation.
Women of reproductive age who undergo cytotoxic chemotherapy have been pretreated with GnRH agonists to reduce the risk of oocyte loss during such therapy and preserve ovarian function. Further studies are necessary to prove that this approach is useful.

# Side effects
Side effects of the GnRH agonists are signs and symptoms of hypoestrogenism, including hot flashes, headaches, and osteoporosis. In patients under long-term therapy, small amounts of estrogens could be given back (add-back regimen) to combat such side effects.
Gemifloxacin dosage and administration
DOSAGE AND ADMINISTRATION
FACTIVE can be taken with or without food and should be swallowed whole with a liberal amount of liquid. The recommended dose of FACTIVE is 320 mg daily, according to the following table (Table 4).
The clinical decision regarding the use of a 5 or 7 day regimen should be guided by results of the initial sputum culture.
The recommended dose and duration of FACTIVE should not be exceeded (see Table 2).
Use in Renally Impaired Patients: Dose adjustment in patients with creatinine clearance >40 mL/min is not required. Modification of the dosage is recommended for patients with creatinine clearance 40 mL/min. Table 5 provides dosage guidelines for use in patients with renal impairment.
Patients requiring routine hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) should receive 160 mg every 24 hours.
When only the serum creatinine concentration is known, the following formula may be used to estimate creatinine clearance.
File:Gmiecalc.jpg
Women: 0.85 x the value calculated for men
Use in Hepatically Impaired Patients: No dosage adjustment is recommended in patients with mild (Child-Pugh Class A), moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment.
Use in Elderly: No dosage adjustment is recommended.
Griseofulvin dosage and administration

# Dosage and Administration
Accurate diagnosis of the infecting organism is essential. Identification should be made either by direct microscopic examination of a mounting of infected tissue in a solution of potassium hydroxide or by culture on an appropriate medium.
Medication must be continued until the infecting organism is completely eradicated as indicated by appropriate clinical or laboratory examination. Representative treatment periods are tinea capitis, 4 to 6 weeks; tinea corporis, 2 to 4 weeks; tinea pedis, 4 to 8 weeks; tinea unguium  depending on rate of growth  fingernails, at least 4 months; toenails, at least 6 months.
General measures in regard to hygiene should be observed to control sources of infection or reinfection. Concomitant use of appropriate topical agents is usually required, particularly in treatment of tinea pedis since in some forms of athlete's foot, yeasts and bacteria may be involved. Griseofulvin will not eradicate the bacterial or monilial infection.

## Adults
A daily dose of 500 mg will give a satisfactory response in most patients with tinea corporis, tinea cruris, and tinea capitis.
For those fungus infections more difficult to eradicate such as tinea pedis and tinea unguium, a daily dose of 1 gram is recommended.

## Children
Approximately 5 mg per pound of body weight per day is an effective dose for most children. On this basis the following dosage schedule for children is suggested:
Children weighing 30 to 50 pounds 125 mg to 250 mg daily.
Children weighing over 50 pounds 250 mg to 500 mg daily.
Haemophilus influenzae pathophysiology

# Pathophysiology

## Etiologic Agent
- Haemophilus influenzae serotype b
Haemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, is a non-motile Gram-negative coccobacillus first described in 1892 by Richard Pfeiffer during an influenza pandemic. It is generally aerobic, but can grow as a facultative anaerobe. H. influenzae was mistakenly considered to be the cause of the common flu until 1933, when the viral etiology of the flu became apparent. Still, H. influenzae is responsible for a wide range of clinical diseases.
Because of its small genome, H. influenzae became the first free-living organism with its entire genome sequenced. Its genome consists of 1,830,140 base pairs of DNA and contains 1740 genes. The method used was Whole genome shotgun. The sequencing project, completed and published in Science in 1995, was conducted at The Institute for Genomic Research.
- Haemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, is a non-motile Gram-negative coccobacillus first described in 1892 by Richard Pfeiffer during an influenza pandemic. It is generally aerobic, but can grow as a facultative anaerobe. H. influenzae was mistakenly considered to be the cause of the common flu until 1933, when the viral etiology of the flu became apparent. Still, H. influenzae is responsible for a wide range of clinical diseases.
- Because of its small genome, H. influenzae became the first free-living organism with its entire genome sequenced. Its genome consists of 1,830,140 base pairs of DNA and contains 1740 genes. The method used was Whole genome shotgun. The sequencing project, completed and published in Science in 1995, was conducted at The Institute for Genomic Research.

## Transmission
- Direct contact with respiratory droplets from nasopharyngeal carrier or case patient
Halofantrine dosage and administration

# Dosage and Administration
(See INDICATIONS AND USAGE.)
Halfan should be given on an empty stomach at least 1 hour before or 2 hours after food. (See WARNINGS.) The recommended dosage regimen to treat adults able to tolerate oral medications, who have mild to moderate malaria caused by P. falciparum or P. vivax is:

### Non-immune Patients
Patients with no previous exposure or minimal exposure to malaria should be considered non-immune. These patients should receive 500 mg (2 x 250 mg tablets) of halofantrine hydrochloride every 6 hours for three doses (total first course dosage 1500 mg). This course of therapy should be repeated 7 days after the first course.

### Semi-immune Patients
Patients with a history of life-long residence in endemic areas and a clear history of recent previous malaria caused by the same Plasmodium species may be considered semi- immune. In these patients, omitting the second course of therapy may be considered. Clinical trials in semi-immune patients have utilized this one-course regimen with satisfactory efficacy and safety.

### Hepatic or Renally Impaired Patients
There is no information on dosing alterations needed because of hepatic or renal impairment.