Persius/hicric huggingface dataset:
AIDS landmark trials

# Overview
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety (or more specifically, information about adverse drug reactions and adverse effects of other treatments) and efficacy data to be collected for health interventions (e.g., drugs, diagnostics, devices, therapy protocols). Several trials have been conducted till date that have immense contribution.

# Landmark Trials

## Clinical Trials of Non-nucleoside Reverse Transcriptase Inhibitors
1. Efavirenz and Nevirapine (2NN study) (2004)
- Purpose : It was a randomised comparison of the non-nucleoside reverse-transcriptase inhibitors (NNRTI) nevirapine and efavirenz.
- Study Design: Randomised trial
2. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1  (ECHO) (2011) 
- Purpose :   Interventional
- Study Design:  Randomised, double-blind, double-dummy, active-controlled trial.

# Registeries
HIV drug resistance database
ATP synthase chain A
ATP synthase F0 subunit 6 (or subunit/chain A) (human gene name ATP6) is a subunit of F0 complex of transmembrane F-type ATP synthase.
This subunit is a key component of the proton channel, and may play a direct role in the translocation of protons across the membrane. Catalysis in the F1 complex depends upon the rotation of the central stalk and F0 c-ring, which in turn is driven by the flux of protons through the membrane via the interface
between the F0 c-ring and subunit A. The peripheral stalk links subunit A to the external surface of the F1 domain, and is thought to act as a stator to counter the tendency of subunit A and the F1alpha(3)beta(3) catalytic portion to rotate with the central rotary element.
3D structure of E.coli homologue of this subunit was modelled based on electron microscopy data (chain M of PDB: 1c17). It forms a transmembrane 4--bundle.
Abacavir description

# Description
ZIAGEN is the brand name for abacavir sulfate, a synthetic carbocyclic nucleoside analogue with inhibitory activity against HIV-1. The chemical name of abacavir sulfate is (1S,cis)-4--2-cyclopentene-1-methanol sulfate (salt) (2:1). Abacavir sulfate is the enantiomer with 1S, 4R absolute configuration on the cyclopentene ring. It has a molecular formula of (C14H18N6O)2H2SO4 and a molecular weight of 670.76 daltons. It has the following structural formula:
Abacavir sulfate is a white to off-white solid with a solubility of approximately 77 mg/mL in distilled water at 25C. It has an octanol/water (pH 7.1 to 7.3) partition coefficient (log P) of approximately 1.20 at 25C.
ZIAGEN Tablets are for oral administration. Each tablet contains abacavir sulfate equivalent to 300 mg of abacavir as active ingredient and the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablets are coated with a film that is made of hypromellose, polysorbate 80, synthetic yellow iron oxide, titanium dioxide, and triacetin.
ZIAGEN Oral Solution is for oral administration. Each milliliter (1 mL) of ZIAGEN Oral Solution contains abacavir sulfate equivalent to 20 mg of abacavir (i.e., 20 mg/mL) as active ingredient and the following inactive ingredients: artificial strawberry and banana flavors, citric acid (anhydrous), methylparaben and propylparaben (added as preservatives), propylene glycol, saccharin sodium, sodium citrate (dihydrate), sorbitol solution, and water.
In vivo, abacavir sulfate dissociates to its free base, abacavir. All dosages for ZIAGEN are expressed in terms of abacavir.
Hepatojugular reflux
Synonyms and keywords: Abdominojugular test, AJR, HJR

# Overview
The abdominojugular test (AJR), also known as hepatojugular reflux or HJR is used as an alternate test for measuring jugular venous pressure (JVP) through the distension or swelling of the jugular vein.  A positive AJR best correlates with the pulmonary capillary wedge pressure although it also correlates with the right heart pressure and the left heart ejection fraction .

# Procedure
The doctor presses firmly over either the Right upper quadrant (liver) or over the center of the abdomen  for 10-60 seconds with a pressure of 20 to 35 mm Hg while observing the internal jugular vein in the neck and also observing to be sure the patient does not Valsalva .
The internal jugular vein can be distinguished from the carotid artery by
- Having a biphasic waveform
- Falling pressure during inspiration
- Rising with abdominal pressure, and
- Being compressible with direct pressure .
When the meniscus of the internal jugular vein cannot be determined, one study found the height of the meniscus in the external jugular vein correlated with the right atrial pressure .
- Negative Result: On an otherwise healthy individual, the jugular venous pressure remains constant or temporarily rises for a heartbeat or two, before returning to normal. This negative result would be indicated by a lack of swelling of the jugular vein.
- Positive Result: A positive result is variously defined as either a sustained rise in the JVP of at least 4cm or more  or a fall of 4 cm or more  after the examiner releases pressure. The AJR has a reported sensitivity of 24%  to 72%  and a specificity of 96% to 93%. The large discrepancy in sensitivity may be explained by the higher value being reported during performance in optimal conditions of a cardiac lab while the lower value was from a study in an emergency room.
Below is a video demonstrating hepato-jugular reflux
Acanthosis nigricans

# Overview
Acanthosis nigricans is a brown to black, poorly defined, velvety hyperpigmentation of the skin, usually present in the posterior and lateral folds of the neck, the axilla, groin, umbilicus, and other areas. Acanthosis nigricans generally occurs due to insulin spillover (from excessive production due to obesity or insulin resistance) onto the skin which results in abnormal skin growth 
The most common cause of acanthosis nigricans is insulin resistance, usually from type 2 diabetes mellitus.Involvement of mucous membranes is rare and suggests a coexisting malignant condition.

# Causes

## Life Threatening Causes
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

## Common Causes
- Diabetes mellitus
- Drug-induced
- Gastric cancer
- Idiopathic
- Insulin resistance
- Obesity
- Polycystic ovary syndrome

## Causes by Organ System

## Causes in Alphabetical Order

# Diagnosis
Physicians can usually diagnose acanthosis nigricans by simply looking at a patient's skin. A skin biopsy may be needed in unusual cases. If no clear cause of acanthosis nigricans is obvious, it may be necessary to search for one. Blood tests, an endoscopy, or x-rays may be required to eliminate the possibility of diabetes or cancer as the cause.

## Physical Examination

### Skin
- Acanthosis nigricans.  With permission from Dermatology Atlas.
- Acanthosis nigricans.  With permission from Dermatology Atlas.
- Acanthosis nigricans.  With permission from Dermatology Atlas.
- Acanthosis nigricans.  With permission from Dermatology Atlas.
- Acanthosis nigricans.  With permission from Dermatology Atlas.
- Acanthosis nigricans.  With permission from Dermatology Atlas.
- Acanthosis nigricans.  With permission from Dermatology Atlas.
- Acanthosis nigricans.  With permission from Dermatology Atlas.
- Acanthosis nigricans.  With permission from Dermatology Atlas.
- Acanthosis nigricans.  With permission from Dermatology Atlas.
- Acanthosis nigricans.  With permission from Dermatology Atlas.

### Pseudoacanthosis Nigricans
- Pseudo-acanthosis nigricans. With permission from Dermatology Atlas.
- Pseudo-acanthosis nigricans. With permission from Dermatology Atlas.
- Pseudo-acanthosis nigricans. With permission from Dermatology Atlas.
- Pseudo-acanthosis nigricans. With permission from Dermatology Atlas.
- Pseudo-acanthosis nigricans. With permission from Dermatology Atlas.

# Treatment
People with acanthosis nigricans should be screened for diabetes and, although rare, cancer. Controlling blood glucose levels through exercise and diet often improves symptoms.

# Prognosis
Acanthosis nigricans often fades if the underlying cause can be determined and treated appropriately.
Supernumerary nipple

# Overview
A supernumerary nipple (also known as a third nipple, triple nipple, thripple, accessory nipple, polythelia or polymastia) is an additional nipple occurring in mammals, including humans. Often mistaken for moles, supernumerary nipples are diagnosed at a rate of 1 in 18 humans.

# Diagnosis

## Physical Examination
The nipples appear along the two vertical "milk lines", which start in the armpit on each side, run down through the typical nipples and end at the groin. They are classified into eight levels of completeness from a simple patch of hair to a milk-bearing breast in miniature. 

### Skin
- Supernumerary nipples. Adapted from Dermatology Atlas.
- Supernumerary nipples. Adapted from Dermatology Atlas.
- Supernumerary nipples. Adapted from Dermatology Atlas.
- Supernumerary nipples. Adapted from Dermatology Atlas.
- Supernumerary nipples. Adapted from Dermatology Atlas.
- Supernumerary nipples. Adapted from Dermatology Atlas.
- Supernumerary nipples. Adapted from Dermatology Atlas.
- Supernumerary nipples. Adapted from Dermatology Atlas.
- Supernumerary nipples. Adapted from Dermatology Atlas.
- Supernumerary nipples. Adapted from Dermatology Atlas.
Polythelia refers to the presence of an additional nipple alone while polymastia denotes the much rarer presence of additional mammary glands.
Although usually presenting on the milk line, pseudomamma can appear as far away as the foot.
A possible relationship with mitral valve prolapse has been proposed.
Acetyldihydrocodeine

# Overview
Acetyldihydrocodeine is an opiate derivative discovered in Germany in 1914 and was used  as a cough suppressant and analgesic. It is not commonly used, but has activity similar to other opiates. Acetyldihydrocodeine is a very close relative derivative of Thebacon, where only the 6-7 double bond is unsaturated. Acetyldihydrocodeine can be described as the 6-acetyl derivative of dihydrocodeine and is metabolised in the liver by demethylation and deacetylation to produce dihydromorphine.
Since acetyldihydrocodeine has higher lipophilicity than codeine and is converted into dihydromorphine rather than morphine, it can be expected to be more potent and longer lasting, and also have higher bioavailability than codeine. Side effects are similar to those of other opiates and include itching, nausea and respiratory depression.
Although an opioid of low to moderate strength and use in medicine elsewhere in the world, acetyldihydrocodeine is a Schedule I controlled substance in the United States. Its DEA Administrative Controlled Substances Control Number is 9051 and the one salt in use, acetyldihydrocodeine hydrochloride, has a freebase conversion ratio of 0.90.  The 2013 annual production quota from the DEA is 2 grammes.
Actinomyces overview

# Overview
Actinomyces is a genus of Gram-positive bacteria. Some species are anaerobic, while others are facultatively anaerobic . Actinomyces species do not form spores, and, while individual bacteria are rod-shaped, morphologically Actinomyces colonies form fungus-like branched networks of hyphae.
Many Actinomyces species are opportunistic pathogens of humans and other mammals, particularly in the oral cavity. In rare cases, these bacteria can cause actinomycosis, a disease characterized by the formation of abscesses in the mouth, lungs, or the gastrointestinal tract.
Some species are responsible for the smell of topsoil, which is often particularly noticeable after rain.
Functional hyperemia
Functional hyperemia, or active hyperemia, is the increased blood flow that occurs when tissue is active.
When cells within the body are active in one way or another, they use more oxygen and fuel, such as glucose or fatty acids, than when they are not. The blood vessels compensate for this metabolism by dilatation, allowing more blood to reach the tissue. This prevents deprivation of the tissue.
Since most of the common nutrients in the body are converted to carbon dioxide when they are metabolized, smooth muscle around blood vessels relax in response to increased concentrations of carbon dioxide within the blood and surrounding interstitial fluid. The relaxation of this smooth muscle results in vascular dilation and increased blood flow.
Some tissues require oxygen and fuel more quickly or in greater quantities. Examples of tissues and organs that are known to have specialized mechanisms for functional hyperemia include:
- The brain through the neuron-dependent hemodynamic response.
- Penile erection tissue by release of nitric oxide.
Laryngeal prominence
The Adam's appleclinically known as the laryngeal prominenceis a feature of the human neck.  This lump, or protrusion, is formed by the angle of the thyroid cartilage surrounding the larynx.

# Sex differences
The laryngeal prominence is usually more prominent in adult men than in women or prepubescent girls or boys.  Note that the growth of the larynx itself during puberty is responsible for the vocal instability in teenage boys, not the laryngeal prominence.  The laryngeal prominence is merely the protrusion one sees of the thyroid cartilage making up the body of the larynx.  Some suggest that the reason for the laryngeal prominence usually being more prominent in males is that the two laminae of the thyroid cartilage that form the protrusion meet at an angle of 90 in males but that angle is usually 120 in females.  This theory, however, seems more like conjecture when the fact is taken into consideration that with most women with a large laryngeal prominence appear no different from those seen on men.
A prominent laryngeal prominence is commonly considered a male secondary sex characteristic though this is more of a perception because not all males have large laryngeal prominence and quite a few women do.

# Surgery
The laryngeal prominence can be more prominent than desired, and this is sometimes remedied by a chondrolaryngoplasty (thyroid chondroplasty), a type of plastic surgery to reduce the size of the laryngeal prominence. This surgery is not without risk as it can adversely affect the voice and cause permanent damage as well as leaving a visible scar. This surgery can also be part of sex reassignment therapy for male-to-female transgender or transsexual people (transwomen).

# "Adam's apple" Etymology
"Adam's apple" is a reference to forbidden fruit in the biblical book of Genesis and in the holy Qur'an.
Adapter molecule crk
Adapter molecule crk also known as proto-oncogene c-Crk or p38 is a protein that in humans is encoded by the CRK gene.
The CRK protein participates in the Reelin signaling cascade downstream of DAB1.

# Function
Adapter molecule crk is a member of an adapter protein family that binds to several tyrosine-phosphorylated proteins. This protein has several SH2 and SH3 domains (src-homology domains) and is involved in several signaling pathways, recruiting cytoplasmic proteins in the vicinity of tyrosine kinase through SH2-phosphotyrosine interaction. The N-terminal SH2 domain of this protein functions as a positive regulator of transformation whereas the C-terminal SH3 domain functions as a negative regulator of transformation. Two alternative transcripts encoding different isoforms with distinct biological activity have been described.
Crk together with CrkL participates in the Reelin signaling cascade downstream of DAB1.
v-Crk, a transforming oncoprotein from avian sarcoma viruses, is a fusion of viral "gag" protein with the SH2 and SH3 domains of cellular Crk. The name Crk is from "CT10 Regulator of Kinase" where CT10 is the avian virus from which was isolated a protein, lacking kinase domains, but capable of stimulating phosphorylation of tyrosines in cells.
Crk should not be confused with Src, which also has cellular (c-Src) and viral (v-Src) forms and is involved in some of the same signaling pathways but is a protein tyrosine-kinase.

# Interactions
CRK (gene) has been shown to interact with:
- BCAR1,
- Cbl gene,
- Dock180,
- EPS15,
- Epidermal growth factor receptor,
- Grb2,
- IRS4,
- MAP4K1,
- MAPK8,
- NEDD9,
- PDGFRA,
- PDGFRB,
- PTK2,
- Paxillin
- RAPGEF1,
- RICS,
- SH3KBP1,  and
- SOS1.
Adefovir description

# Description
HEPSERA is the tradename for adefovir dipivoxil, a diester prodrug of adefovir. Adefovir is an acyclic nucleotide analog with activity against human hepatitis B virus (HBV).
The chemical name of adefovir dipivoxil is 9--phosphinyl]-methoxy]ethyl]adenine. It has a molecular formula of C20H32N5O8P, a molecular weight of 501.48 and the following structural formula:
Adefovir dipivoxil is a white to off-white crystalline powder with an aqueous solubility of 19 mg/mL at pH 2.0 and 0.4 mg/mL at pH 7.2. It has an octanol/aqueous phosphate buffer (pH 7) partition coefficient (log p) of 1.91.
HEPSERA tablets are for oral administration. Each tablet contains 10 mg of adefovir dipivoxil and the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, pregelatinized starch, and talc.
Alendronate overdose

# Overdose information
Lethal dose
Treatment

## Lethal dose
Significant lethality after single oral doses was seen in female rats and mice at
552 mg/kg (3256 mg/m2) and 966 mg/kg (2898 mg/m2), respectively. In males, these
values were slightly higher, 626 and 1280 mg/kg, respectively. There was no lethality
in dogs at oral doses up to 200 mg/kg (4000 mg/m2). Return to top

## Treatment
No specific information is available on the treatment of overdosage with
FOSAMAX. Hypocalcemia, hypophosphatemia, and upper gastrointestinal adverse
events, such as upset stomach, heartburn, esophagitis, gastritis, or ulcer, may result
from oral overdosage. Milk or antacids should be given to bind alendronate. Due to
the risk of esophageal irritation, vomiting should not be induced and the patient
should remain fully upright.
Dialysis would not be beneficial. Return to top
Adapted from the FDA Package Insert.
Alfredo R.A. Bengzon
Alfredo R.A. Bengzon is a Filipino doctor, educator, and former public official. He is currently Vice President for the Professional Schools of the Ateneo de Manila University, dean of the Ateneo School of Medicine and Public Health, dean emeritus of the Ateneo Graduate School of Business, and President and CEO of The Medical City.

# Education
Bengzon graduated from the Ateneo de Manila in 1956 with  a bachelor of arts degree. He attended the University of the Philippines where he got his doctor of medicine degree, and then completed his master of business administration degree at the Ateneo Graduate School of Business in 1972.

# Career
Bengzon has had a long and distinguished career not only as a neurologist but also as leader and manager in both private and public sectors.
He was Secretary of Health, Peace Commissioner, and Vice Chair of the Philippine Negotiating Panel for the U.S. Military Facilities during the presidency of Corazon C. Aquino. He has also served as chief operating officer of several private companies engaged in health services. 
In 1993, Bengzon was appointed Dean of the Ateneo Graduate School of Business and Vice President for the Professional Schools of the Ateneo de Manila University.
His most current position is President and CEO of The Medical City in Pasig City.

# Recognition
In 1989, Bengzon was awarded the degree of Doctor of Science (honoris causa) by the Ateneo de Manila. 
In 1991, he was conferred the Ramon Magsaysay Award.
Alipogene tiparvovec

# Overview
Alipogene tiparvovec (marketed under the trade name Glybera) is a gene therapy treatment that compensates for lipoprotein lipase deficiency (LPLD), which can cause severe pancreatitis. In July 2012, the European Medicines Agency recommended it for approval, the first recommendation for a gene therapy treatment in either Europe or the United States. The recommendation was endorsed by the European Commission in November 2012 and commercial rollout is expected in late 2013.

# Mechanism
The adeno-associated virus serotype 1 (AAV1) viral vector delivers an intact copy of the human lipoprotein lipase (LPL) gene.  Data from the clinical trials indicates that fat concentrations in blood were reduced between 3 and 12 weeks after injection, in nearly all patients.  The advantages of AAV include apparent lack of pathogenicity, delivery to non-dividing cells, and non-integrating in contrast to retroviruses, which show random insertion with accompanying risk of cancer.  AAV also presents very low immunogenicity, mainly restricted to generating neutralizing antibodies, and little well defined cytotoxic response. The cloning capacity of the vector is limited to replacement of the virus's 4.8 kilobase genome.

# Cost
Alipogene tiparvovec is expected to cost around $1.6 million for treatment which will make it the most expensive medicine in the world.

# See Also
- Gene Therapy
Alkaline earth metal
The alkaline earth  metals are a series of elements comprising Group 2 (IUPAC style) of the periodic table: beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba) and radium (Ra). The alkaline earth metals provide a good example of group trends in properties in the periodic table, with well characterised homologous behaviour down the group.
The alkaline earth metals are silvery colored, soft metals, which react readily with halogens to form ionic salts, and with water, though not as rapidly as the alkali metals, to form strongly alkaline (basic) hydroxides. For example, where sodium and potassium react with water at room temperature, magnesium reacts only with steam and calcium with hot water:
Beryllium is an exception: It does not react with water or steam, and its halides are covalent.
All the alkaline earth metals have two electrons in their outermost shell, so the energetically preferred state of achieving a filled electron shell is to lose two electrons to form doubly charged positive ions.
The alkaline earth metals are named after their oxides, the alkaline earths, whose old-fashioned names were beryllia, magnesia, lime, strontia and baryta.  These oxides are basic (alkaline) when combined with water. "Earth" is an old term applied by early chemists to nonmetallic substances that are insoluble in water and resistant to heating--properties shared by these oxides. The realization that these earths were not elements but compounds is attributed to the chemist Antoine Lavoisier.  In his Traite Elementaire de Chimie (Elements of Chemistry) of 1789 he called them salt-forming earth elements. Later, he suggested that the alkaline earths might be metal oxides, but admitted that this was mere conjecture.  In 1808, acting on Lavoisier's idea, Humphry Davy became the first to obtain samples of the metals by electrolysis of their molten earths.

# Biological occurrences
- Beryllium's low aqueous solubility means it is rarely available to biological systems - it has no known role in living organisms, and when encountered by them, is generally highly toxic.
- Magnesium and calcium are ubiquitous and essential to all known living organisms. They are involved in more than one role, with for example Mg/Ca ion pumps playing a role in some cellular processes such as modern day batteries, magnesium functioning as the active center in some enzymes, and calcium salts taking a structural role (e.g. bones).
- Strontium and barium have a lower availability in the biosphere. They generally have no natural role in biological systems, (perhaps the only documented example is the primitive marine organism Acantharea, which uses strontium sulphate to build its exoskeleton). These elements have some uses in medicine, for example "barium meals" in radiographic imaging, whilst strontium compounds are employed in some toothpastes.
- Radium has a low availability and is highly radioactive, making it toxic to life.